Journal Of Comparative Neurology

Cytoarchitecture, areas, and neuron numbers of the etruscan shrew cortex.

Publication Date: 2012 Jan 17 PMID: 22252518
Authors: Naumann, R. K. - Anjum, F. - Roth-Alpermann, C. - Brecht, M.
Journal: J Comp Neurol

The Etruscan shrew, Suncus etruscus, is one of the smallest mammals. Etruscan shrews can recognize prey shape with amazing speed and accuracy, based on whisker-mediated tactile cues. Because of its small size quantitative analysis of the Etruscan shrew cortex is more tractable than in other animals. To quantitatively assess the anatomy of the Etruscan shrew's brain we sectioned brains and applied Nissl staining and NeuN (neuronal nuclei) antibody staining. On basis of these stains we estimated the number of neurons of ten cortical hemispheres using Stereoinvestigator and Neurolucida (MBF Bioscience) software. On average the neuron number per hemisphere was found to be approximately 1 million. We also measured cortical surface area and found an average of 11.1 mm(2) (n = 7) and an average volume of 5.3 mm(3) (n = 10) per hemisphere. We identified 13 cortical regions by cytoarchitectonic boundaries in coronal, sagittal, and tangential sections processed for Nissl substance, myelin, cytochrome oxidase, ionic zinc, neurofilaments and vesicular glutamate transporter 2 (VGluT2). The Etruscan shrew is a highly tactile animal with a large somatosensory cortex, which contains a barrel field, but barrels are much less clearly defined than in rodents. The anatomically derived cortical partitioning scheme roughly corresponds to physiologically derived maps of neocortical sensory areas. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Genomics of mature and immature olfactory sensory neurons.

Publication Date: 2012 Jan 17 PMID: 22252456
Authors: Nickell, M. D. - Breheny, P. - Stromberg, A. J. - McClintock, T. S.
Journal: J Comp Neurol

The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. 847 immature OSN-specific and 691 mature OSNspecific genes were identified. Control of gene expression by chromatin modification and transcription factors, along with neurite growth, protein transport, RNA processing, cholesterol biosynthesis, and apoptosis via death domain receptors were overrepresented biological processes in immature OSNs. Ion transport (ion channels), presynaptic functions, and cilia-specific processes were overrepresented in mature OSNs. Processes overrepresented among the genes expressed by all OSNs were protein and ion transport, ER overload response, protein catabolism, and the electron transport chain. To more accurately represent gradations in mRNA abundance and identify all genes expressed in each cell type, classification methods were used to produce probabilities of expression in each cell type for every gene. These probabilities, which identified 9,300 genes expressed in OSNs, were 96% accurate at identifying genes expressed in OSNs and 86% accurate at discriminating genes specific to mature and immature OSNs. This OSN gene database not only predicts the genes responsible for the major biological processes active in OSNs, but also identifies thousands of never before studied genes that support OSN phenotypes. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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GIRK2 expression in dopamine neurons of the substantia nigra and ventral tegmental area.

Publication Date: 2012 Jan 17 PMID: 22252428
Authors: Reyes, S. - Fu, Y. - Double, K. - Thompson, L. - Kirik, D. - Paxinos, G. - Halliday, G. M.
Journal: J Comp Neurol

G-protein regulated inward-rectifier potassium channel 2 (GIRK2) is reported to be expressed only within certain dopamine neurons of the substantia nigra (SN), although very limited data are available in humans. We examined the localization of GIRK2 in the SN and adjacent ventral tegmental area (VTA) of humans and mice using either neuromelanin pigment or immunolabeling with tyrosine hydroxylase (TH) or calbindin. GIRK2 immunoreactivity was found in nearly every human pigmented neuron or mouse TH-immunoreactive neuron in both the SN and VTA, although considerable variability in the intensity of GIRK2 staining was observed. The relative intensity of GIRK2 immunoreactivity in TH-immunoreactive neurons was determined and in both species nearly all SN TH-immunoreactive neurons had strong GIRK2 immunoreactivity compared with only 50-60% of VTA neurons. Most paranigral VTA neurons also contained calbindin immunoreactivity and approximately 25% of these and nearby VTA neurons also had strong GIRK2 immunoreactivity. These data show that high amounts of GIRK2 protein are found in most SN neurons as well as in a proportion of nearby VTA neurons. The single previous human study may have been compromised by the fixation method used and the post-mortem delay of their controls, while other studies suggesting GIRK2 is located only in limited neuronal groups within the SN have erroneously included VTA regions as part of the SN. In particular, the dorsal layer of dopamine neurons directly underneath the red nucleus is considered a VTA region in humans but is commonly considered the dorsal tier of the SN in laboratory species. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Regional and subcellular distribution of the receptor-targeting protein PIST in the rat central nervous system.

Publication Date: 2012 Apr 1 PMID: 22250034
Authors: Chen, A. - Gobetaling, E. K. - Witkowski, L. - Bhindi, A. - Bauch, C. - Roussy, G. - Sarret, P. - Kreienkamp, H. J. - Stroh, T.
Journal: J Comp Neurol

A hippocampal neuron in primary culture stained with anti-PIST (red) and anti-neuroligin-2 (green), a postsynaptic cell adhesion protein which is exclusively located at inhibitory synapses. The nucleus was stained with DAPI (blue). Note the typical distribution of neuroligin-2 immunoreactivity reminiscent of inhibitory synapses at proximal dendrites and cell body, which is not matched by the PIST immunofluorescence signal. The latter is concentrated in the perikaryon in a juxtanuclear position and appears to be absent from postsynaptic sites. The Journal of Comparative Neurology, Volume 520, Number 5, pages 889-913.

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Ascending gustatory pathways to the telencephalon in goldfish.

Publication Date: 2012 Jan 13 PMID: 22247053
Authors: Kato, T. - Yamada, Y. - Yamamoto, N.
Journal: J Comp Neurol

Ascending pathways to the telencephalon from the secondary gustatory nucleus (SGN), preglomerular tertiary gustatory nucleus (pTGN) and medial preglomerular nucleus (PGm) were examined by tract-tracing experiments in goldfish Carassius auratus. Tracer injections to the SGN suggest the presence of direct ascending pathways to the supracommissural and the dorsal parts of ventral telencephalic area, and the medial part of dorsal telencephalic area (Dm), restricted to its ventral region. The SGN experiments also suggest projections to the pTGN and PGm, and several neuronal types in the primary gustatory centers were newly found to give rise to ascending fibers to the SGN. Injections to the pTGN suggest reciprocal connections of the nucleus with the dorsal region of Dm (dDm). Injections to the PGm resulted in labeled cells in the dorsal part of SGN, secondary general visceral nucleus, and the posterior part of dorsal telencephalic area, suggesting that this preglomerular nucleus receives gustatory, general visceral, and olfactory inputs. Fibers labeled from the PGm terminated in the central part of the dorsal telencephalic area and dDm; the latter region contained many labeled somata. The terminal zone of PGm fibers in the dDm is located laterally adjacent to that from the pTGN. Injection experiments to the pTGN and PGm also suggest connections of these nuclei with the inferior lobar nuclei and torus lateralis. Based on the results of the present as well as recent studies, an updated map is provided that shows by and large distinct sensory representation within the goldfish dorsal telencephalic area. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Amygdala afferents monosynaptically innervate corticospinal neurones in rat medial prefrontal cortex (mPFC).

Publication Date: 2012 Jan 13 PMID: 22247040
Authors: Gabbott, P. - Warner, T. A. - Brown, J. - Salway, P. - Gabbott, T. - Busby, S.
Journal: J Comp Neurol

The amygdala provides the medial prefrontal cortex (mPFC; areas 25, 32 and 24b) with salient emotional information. This study investigated the synaptic connectivity of identified amygdalocortical boutons (ACBs), (labelled anterogradely following injections of Phaseolus vulgaris leucoagglutinin into the basolateral nucleus of the amygdala), with the dendritic processes of identified layer 5 corticospinal neurones in rat mPFC. The corticospinal (CS) neurones in mPFC had been retrogradely labelled with rhodamine fluorescent latex microspheres and subsequently intracellularly 'filled' with biotinylated lucifer yellow to visualise their basal and apical dendrites. Two main classes of mPFC CS neurones were identified - Type 1 cells had apical dendrites bearing numerous dendritic spines with radiate basal dendritic arbors. Type 2 cells possessed apical dendrites with greatly reduced spine densities and a broad range of basal dendritic tree morphologies. Identified ACBs made asymmetric synaptic junctions with labelled dendritic spines and the labelled apical and basal dendritic shafts of identified CS neurones. On average, 8 ACBs were closely associated with the labelled basal dendritic arbors of Type 1 CS neurones and 5 ACBs with Type 2 CS basal dendrites. The mean Scholl distance of ACBs from CS somata (for both Types 1/2 cells) was 66microm - coinciding with a region containing the highest length density of CS neurone basal dendrites. These results indicate that neurones in the BLA can monosynaptically influence CS neurones in mPFC that project to autonomic regions of the thoracic spinal cord and probably to other additional subcortical target regions, such as the lateral hypothalamus. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Brainstem origins of glutamatergic innervation of the rat hypothalamic paraventricular nucleus.

Publication Date: 2012 Jan 15 PMID: 22247025
Authors: Ziegler, D. R. - Edwards, M. R. - Ulrich-Lai, Y. M. - Herman, J. P. - Cullinan, W. E.
Journal: J Comp Neurol

Multiple lines of evidence document a role for glutamatergic input to the hypothalamic paraventricular nucleus (PVH) in stress-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. However, the neuroanatomical origins of the glutamatergic input have yet to be definitively determined. We have previously shown that Vesicular Glutamate Transporter 2; VGLUT2) is the predominant VGLUT isoform expressed in the basal forebrain and brainstem, including PVH-projecting regions, and that the PVH is preferentially innervated by VGLUT2-immunoreactive terminals/boutons. In the present study we employed a dual-labeling approach, combining immunolabeling for a retrograde tract-tracer, Fluoro-gold (FG), with in situ hybridization for VGLUT2 mRNA, to map the brainstem and caudal forebrain distribution of glutamatergic PVH-projecting neurons. The present report presents evidence for substantial dual-labeling in the periaqueductal gray, caudal portions of the zona incerta and subparafascicular nucleus, and the lateral parabrachial nucleus. The current data also suggest that relatively few PVH-projecting neurons in ascending raphe nuclei, nucleus of the solitary tract, or ventrolateral medulla are VGLUT2-positive. The data reveal multiple brainstem origins of glutamatergic input to PVH that are positioned to play a role in transducing a diverse range of stressful stimuli. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Lack of robust LGN label following transneuronal rabies virus injections into macaque area V4.

Publication Date: 2012 Jan 11 PMID: 22237967
Authors: Lyon, D. C. - Rabideau, C.
Journal: J Comp Neurol

In primates, retinal inputs are relayed through the magno and parvocells of the lateral geniculate nucleus (LGN) indirectly to extrastriate visual cortex. The most direct pathway identified to extrastriate cortex is a disynaptic one that provides robust magno and parvocellular inputs to area MT. The inclusion of parvocells in this projection is somewhat surprising because of their importance for color and form vision, whereas MT is more strictly tuned to velocity. This raises the question of whether areas more involved in color and form processing, such as V4, receive similar projections. We report here on experiments that use rabies virus injections into V4 to retrogradely label mono and disynaptic inputs. We find only a small number of labeled neurons in the LGN in a pattern consistent with monosynaptic labeling of koniocells, rather than disynaptic labeling of magno and parvocells. The lack of robust magno and parvocellular label was not due to ineffective viral transport since in the same cases we find hundreds of neurons labeled in the thalamic reticular nucleus, a structure which can only be labeled disynaptically from cortex. We also find a complete absence of neurons labeled in V1, but thousands in adjacent areas V2 and V3. This result helps explain the absence of labeled magno and parvocells in LGN because disynaptic transport from an extrastriate visual area should require a relay through V1. Taken together these results suggest that ascending magno/parvocellular inputs to V4 are more hierarchically organized than the relatively direct inputs to MT. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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(+/-)3,4-methylenedioxymethamphetamine ("Ecstacy") treatment modulates expression of neurotrophins and their receptors in multiple regions of adult rat brain.

Publication Date: 2012 Jan 11 PMID: 22237931
Authors: Hemmerle, A. M. - Dickerson, J. W. - Herring, N. R. - Schaefer, T. L. - Vorhees, C. V. - Williams, M. T. - Seroogy, K. B.
Journal: J Comp Neurol

(+/-)3,4-Methylenedioxymethamphetamine (MDMA), a widely used drug of abuse, rapidly reduces serotonin levels in the brain when ingested or administered in sufficient quantities, resulting in deficits in complex route-based learning, spatial learning, and reference memory. Neurotrophins are important for survival and preservation of neurons in the adult brain, including serotonergic neurons. In this study, we examined the effects of MDMA on the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and their respective high affinity receptors, trkB and trkC, in multiple regions of the rat brain. A serotonergic-depleting dose of MDMA (10 mg/kg x 4 at 2-hour intervals on a single day) was administered to adult Sprague-Dawley rats and brains were examined 1, 7, or 24 hours after the last dose. Messenger RNA levels of BDNF, NT-3, trkB and trkC were analyzed using in situ hybridization with cRNA probes. The prefrontal cortex was particularly vulnerable to MDMA-induced alterations in that BDNF, NT-3, trkB and trkC mRNAs were all upregulated at multiple time points. MDMA-treated animals had increased BDNF expression in the frontal, parietal, piriform, and entorhinal cortices, increased neurotrophin-3 expression in the anterior cingulate cortex, and elevated trkC in the entorhinal cortex. In the nigrostriatal system, BDNF expression was upregulated in the substantia nigra pars compacta and trkB was elevated in the striatum in MDMA-treated animals. Both neurotrophins and trkB were differentially regulated in several regions of the hippocampal formation. These findings suggest a possible role for neurotrophin signaling in learning and memory deficits seen following MDMA treatment. (c) 2012 Wiley-Liss, Inc.

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A quantitative analysis of neocortical gyrencephaly in African elephants (Loxodonta africana) and six species of cetaceans: Comparison to other mammals.

Publication Date: 2012 Jan 11 PMID: 22237903
Authors: Manger, P. R. - Prowse, M. - Haagensen, M. - Hemingway, J.
Journal: J Comp Neurol

This study provides quantitative data on the extent of gyrencephaly in the large brained African elephant and several species of cetaceans (from smaller to larger brained) in comparison to other mammals. Across three mammalian orders (primates, carnivores and artiodactyls) the species with the larger brains are more gyrencephalic with each order exhibiting a specific negative allometry. The African elephant, with a 5 kg brain, has a gyrencephalic index (GI) of 3.89, which while highly gyrencephalic is not more so than would be predicted for a mammal with a 5 kg brain. The cetaceans had an average GI of 5.43, are the most gyrencephalic mammals studied to date and are more gyrencephalic than one would predict based in comparison to other mammals. No relationship between brain mass and GI was evident in the cetaceans as seen in other mammals, with all cetaceans showing similar GIs irrespective of brain mass (range of GI 5.23 - 5.70, range of brain mass 577 - 5617 g). This is yet another parameter indicating cetaceans to be neuroanatomical outliers. Two species of pinnipeds studied had GIs that were well above that seen for terrestrial carnivores, and the aquatic manatee was close to lissencephalic. Thus, all three groups of marine mammals showed unusual extents of cortical gyrencephaly indicating a morphological alteration of the telencephalon associated with the return to the marine environment. The analysis suggests that cortical thickness and neuronal density are important factors determining the extent of gyrencephaly across mammalian species. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Lack of early pattern stimulation prevents normal development of the alpha (Y) retinal ganglion cell population in cat.

Publication Date: 2012 Jan 11 PMID: 22237852
Authors: Burnat, K. - Van der Gucht, E. - Waleszczyk, W. J. - Kossut, M. - Arckens, L.
Journal: J Comp Neurol

Binocular deprivation of pattern vision (BD) early in life permanently impairs global motion perception. Using the SMI-32 antibody against neurofilament protein (NFP) as a marker of the motion-sensitive Y-cell pathway (Van der Gucht et al., 2001) we analysed the impact of early BD on the retinal circuitry in adult perceptually-characterized cats (Burnat et al., 2005). In controls, large retinal ganglion cells exhibited a strong NFP signal in the soma and the proximal parts of the dendritic arbors. The NFP-immunoreactive dendrites typically branched into sublamina a of the inner plexiform layer (IPL), i.e. the OFF inner plexiform sublamina. In the retina of adult BD cats however, most of the NFP-immunoreactive ganglion cell dendrites branched throughout the entire IPL. The NFP-immunoreactive cell bodies were less regularly distributed, often appeared in pairs and had a significantly larger diameter compared to NFP-expressing cells in control retinas. These remarkable differences in the immunoreactivity pattern were typically observed in temporal retina. In conclusion, we show the anatomical organization typical of premature Y-type retinal ganglion cells persists into adulthood even if normal visual experience follows for years upon an initial six month-period of BD. Binocular pattern deprivation possibly induces a life-long OFF functional domination, normally only apparent during development, putting early high quality vision forward as a premise for proper ON-OFF pathway segregation. These new observations for pattern-deprived animals provide an anatomical basis for the well-described motion perception deficits in congenital cataract patients. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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The impact of chorda tympani nerve injury on cell survival, axon maintenance, and morphology of its terminal field in the nucleus of the solitary tract.

Publication Date: 2012 Jan 11 PMID: 22237830
Authors: Reddaway, R. B. - Davidow, A. W. - Deal, S. L. - Hill, D. L.
Journal: J Comp Neurol

Chorda tympani nerve transection (CTX) has been useful to study the relationship between the nerve and taste buds in fungiform papillae. This work demonstrated that the morphological integrity of taste buds depends on their innervation. While considerable research focused on the effects of CTX on peripheral gustatory structures, much less research has focused on the central effects. Here, we explored how CTX affects ganglion cell survival, maintenance of injured peripheral axons, and its terminal field organization in the nucleus of the solitary tract (NTS). Following CTX in adult rats, the chorda tympani nerve was labeled with biotinylated dextran amine at 3, 7, 14, 30, and 60 days post CTX to enable visualization of the terminal field associated with peripheral processes. There was a significant and persistent reduction of the labeled chorda tympani nerve terminal field volume and density in the NTS following CTX. Compared to controls, the volume of the labeled terminal field was not altered at 3 or 7 days post CTX; however, it was significantly reduced by 44% and by 63% at 30 and 60 days post CTX, respectively. Changes in the density of labeled terminal field in the NTS paralleled the terminal field volume results. The dramatic decrease in labeled terminal field size post CTX cannot be explained by a loss of geniculate ganglion neurons or degeneration of central axons. Instead, the function and/or maintenance of the peripheral axonal process appear to be affected. These new results have implications for long-term functional and behavioral alterations. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Sprouting of colonic afferent central terminals and increased spinal MAP kinase expression in a mouse model of chronic visceral hypersensitivity.

Publication Date: 2012 Jan 11 PMID: 22237807
Authors: Harrington, A. M. - Brierley, S. M. - Isaacs, N. - Hughes, P. A. - Castro, J. - Blackshaw, L. A.
Journal: J Comp Neurol

Visceral pain following infection or inflammation is a major clinical problem. Although we have knowledge regarding how peripheral endings of colonic afferents change in disease, their central projections have been overlooked. Using neuroanatomical tracing and colorectal distension (CRD) we aimed to identify colonic afferent central terminals (CACTs), the dorsal horn (DH) neurons activated by colonic stimuli in the thoracolumbar (T10-L1) DH, and determine how they are altered by post-inflammatory chronic colonic mechanical hypersensitivity. Retrograde tracing from the colon identified CACTs in the DH, whilst immunohistochemistry for phosphorylated MAP kinase ERK1/2 (pERK) identified DH neurons activated by CRD (80 mmHg). In healthy mice, CACTs were primarily located in DH lamina I (LI), V (LV) and projected down mid and lateral DH collateral pathways. CRD evoked pERK-immunoreactivity in DH neurons, the majority of which were located in LI and LV, the same regions as CACTs. In post-inflammatory mice CACTs were significantly increased in T12-L1 compared to healthy mice. Whilst CACTs remained abundant in LI, they were more widespread and now present in deeper laminae. Following CRD significantly more DH neurons were pERK-IR post-inflammation (T12-L1), with abundant expression in LI and deeper laminae. In both healthy and post-inflammatory mice many pERK neurons were in close apposition to CACTs, suggesting colonic afferents can stimulate specific DH neurons in response to noxious CRD. Overall, we demonstrate CACT density and the number of responsive DH neurons in the spinal cord increases post-inflammation, which may facilitate aberrant central representation of colonic nociceptive signaling following chronic peripheral hypersensitivity. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Efferent projections of C3 adrenergic neurons in the rat central nervous system.

Publication Date: 2012 Jan 11 PMID: 22237784
Authors: Sevigny, C. P. - Bassi, J. - Williams, D. A. - Anderson, C. R. - Thomas, W. G. - Allen, A. M.
Journal: J Comp Neurol

C3 neurons constitute one of three known adrenergic nuclei in the rat central nervous system (CNS). While the adrenergic C1 cell group has been extensively characterized both physiologically and anatomically, the C3 nucleus has remained relatively obscure. This study employed a lentiviral tracing technique which expresses green fluorescent protein behind a promoter selective to noradrenergic and adrenergic neurons. Microinjection of this virus into the C3 nucleus enabled the selective tracing of C3 efferents throughout the rat CNS, thus revealing the anatomical framework of C3 projections. C3 terminal fields were observed in over forty different CNS nuclei, spanning all levels of the spinal cord, as well as various medullary, mesencephalic, hypothalamic, thalamic, and telencephalic nuclei. The highest densities of C3 axon varicosities were observed in Lamina X and the intermediolateral cell column of the thoracic spinal cord, as well as the dorsomedial medulla (both commissural and medial nuclei of the solitary tract, area postrema, and the dorsal motor nucleus of the vagus), ventrolateral periaqueductal gray, dorsal parabrachial nucleus, periventricular and rhomboid nuclei of the thalamus, and paraventricular and periventricular nuclei of the hypothalamus. In addition, moderate and sparse projections were observed in many catecholaminergic and serotonergic nuclei, as well as the area anterior and ventral to the third ventricle, Lamina X of the cervical, lumbar and sacral spinal cord, and various hypothalamic and telencephalic nuclei. The anatomical map of C3 projections detailed in this survey hopes to lay the first steps towards developing a functional framework for this nucleus. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Structural plasticity of hippocampal mossy fiber synapses as revealed by high-pressure freezing.

Publication Date: 2012 Jan 11 PMID: 22237743
Authors: Zhao, S. - Studer, D. - Chai, X. - Graber, W. - Brose, N. - Nestel, S. - Young, C. - Rodriguez, E. P. - Saetzler, K. - Frotscher, M.
Journal: J Comp Neurol

Despite recent progress in fluorescence microscopy techniques, electron microscopy (EM) is still superior in the simultaneous analysis of all tissue components at high resolution. However, it is unclear to what extent conventional fixation for EM using aldehydes results in tissue alteration. Here, we made an attempt to minimize tissue alteration by using rapid high-pressure freezing (HPF) of hippocampal slice cultures. We used this approach to monitor fine-structural changes at hippocampal mossy fiber synapses associated with chemically induced long-term potentiation (LTP). Synaptic plasticity in LTP has been known to involve structural changes at synapses including reorganization of the actin cytoskeleton and de novo formation of spines. While LTP-induced formation and growth of postsynaptic spines have been reported, little is known about associated structural changes in presynaptic boutons. Mossy fiber synapses are assumed to exhibit presynaptic LTP expression and are easily identified by EM. In slice cultures from wild-type mice, we found that chemical LTP increased the length of the presynaptic membrane of mossy fiber boutons, associated with a de novo formation of small spines and an increase in the number of active zones. Of note, these changes were not observed in slice cultures from Munc13-1 knock-out mutants exhibiting defective vesicle priming. These findings show that activation of hippocampal mossy fibers induces pre- and postsynaptic structural changes at mossy fiber synapses that can be monitored by EM. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Physiological and anatomical evidence for an inhibitory trigemino-oculomotor pathway in the cat.

Publication Date: 2012 Jan 11 PMID: 22237697
Authors: May, P. J. - Vidal, P. P. - Baker, H. - Baker, R.
Journal: J Comp Neurol

During blink down-phase, the levator palpebrae superioris (levator) muscle is inactivated, allowing the orbicularis oculi muscle to act. For trigeminal reflex blinks, the excitatory connections from trigeminal sensory nuclei to the facial nucleus have been described, but the pathway whereby the levator is turned off have not. We examined this question by use of both physiological and anatomical approaches in the cat. Intracellular records from antidromically activated levator motoneurons revealed that periorbital electrical stimulation produced bilateral, long latency IPSPs. Central electrical stimulation of the principal trigeminal nucleus produced shorter latency IPSPs. Intracellular staining revealed that these motoneurons reside in the caudal central subdivision and have 10 or more poorly branched dendrites, which extend bilaterally into the surrounding supraoculomotor area. Axons penetrated in this region could be activated from periorbital and central electrodes. Neurons labeled from tracer injections into the caudal oculomotor complex were distributed in a crescent-shaped band that lined the ventral and rostral aspects of the pontine trigeminal sensory nucleus. Double label immunohistochemical procedures demonstrated that these cells were not tyrosine hydoxylase positive cells in the Kolliker-Fuse area. Instead, supraorbital nerve afferents displayed a similar crescent-shaped distribution, suggesting they drive these trigemino-oculomotor neurons. Anterograde labeling of the trigemino-oculomotor projection indicates that it terminates bilaterally, in and above the caudal central subdivision. These results characterize a trigemino-oculomotor pathway which inhibits levator palpebrae motoneurons in response to blink producing periorbital stimuli. The bilateral distributions of trigemino-oculomotor afferents, levator motoneurons and their dendrites supply a morphological basis for conjugate lid movements. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Synaptic plasticity in the medial superior olive of hearing, deaf, and cochlear-implanted cats.

Publication Date: 2012 Jan 11 PMID: 22237661
Authors: Tirko, N. N. - Ryugo, D. K.
Journal: J Comp Neurol

The medial superior olive (MSO) is a key auditory brainstem structure that receives binaural inputs and is implicated in processing interaural time disparities used for sound localization. The deaf white cat, a proven model of congenital deafness, was used to examine how deafness and cochlear implantation affected the synaptic organization at this binaural center in the ascending auditory pathway. The patterns of axosomatic and axodendritic organization were determined for principal neurons from the MSO of hearing, deaf, and deaf cats with cochlear implants. The nature of the synapses was evaluated through electron microscopy, ultrastructure analysis of the synaptic vessels and immunohistochemistry. Results show that the proportion of inhibitory axosomatic terminals was significantly smaller in deaf animals when compared to hearing animals. However, after a period of electrical stimulation via cochlear implants, the proportion of inhibitory inputs resembled that of hearing animals. Additionally, the excitatory axodendritic boutons of hearing cats were found to be significantly larger than those of deaf cats. Boutons of stimulated cats were significantly larger than the boutons in deaf cats, though not as large as in the hearing cats, indicating a partial recovery of excitatory inputs to MSO dendrites after stimulation. These results exemplify dynamic plasticity in the auditory brainstem and reveal that electrical stimulation through cochlear implants has a restorative effect on synaptic organization in the MSO. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Different classes of input and output neurons reveal new features in microglomeruli of the adult Drosophila mushroom body calyx.

Publication Date: 2012 Jan 11 PMID: 22237598
Authors: Butcher, N. J. - Friedrich, A. B. - Lu, Z. - Tanimoto, H. - Meinertzhagen, I. A.
Journal: J Comp Neurol

To investigate how sensory information is processed, transformed, and stored within an olfactory system, we examined the anatomy of the input region, the calyx, of the mushroom bodies of Drosophila melanogaster. These paired structures are important for various behaviors, including olfactory learning and memory. Cells in the input neuropile, the calyx, are organized into an array of microglomeruli each comprising the large synaptic bouton of a projection neuron (PN) from the antennal lobe surrounded by tiny postsynaptic neurites from intrinsic Kenyon cells. Extrinsic neurons of the mushroom body also contribute to the organization of microglomeruli. We employed a combination of genetic reporters to identify single cells in the Drosophila calyx by light microscopy, and compared these with cell shapes, synapses and circuits derived from serial-section EM. We identify three morphological types of PN boutons, uni-lobed, clustered, and elongated; define three ultrastructural types, with clear- or dense-core vesicles and those with a dark cytoplasm having both; reconstruct diverse dendritic specializations of Kenyon cells; and identify Kenyon cell presynaptic sites upon extrinsic neurons. We also report new features of calyx synaptic organization, in particular extensive serial synapses that link calycal extrinsic neurons into a local network, and the numerical proportions of synaptic contacts between calycal neurons. All PN bouton types had more ribbon than non-ribbon synapses, dark boutons particularly so, and ribbon synapses were larger and with more postsynaptic elements (2-14) than non-ribbon (1-10). The numbers of elements were in direct proportion to presynaptic membrane area. Extrinsic neurons exclusively had ribbon synapses. J. Comp. Neurol., 2012. (c) 2012 Wiley-Liss, Inc.

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Regeneration of olfactory afferent axons in the locust brain.

Publication Date: 2012 Mar 1 PMID: 22223456
Authors: Stern, M. - Scheiblich, H. - Eickhoff, R. - Didwischus, N. - Bicker, G.
Journal: J Comp Neurol

Confocal image of a locust brain 14 days after one antenna had been crushed. Antennal afferents were anterogradely labeled with Neurobiotin (magenta). Aberrantly regenerated olfactory receptor axons have grown through the antennocerebral tract into the mushroom body. Counterstaining: phalloidin (green) and DAPI (blue). The Journal of Comparative Neurology, Volume 520, Number 4, pages 679-693.

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Transition continues.

Publication Date: 2012 Feb 1 PMID: 22120899
Authors: Hof, P. R.
Journal: J Comp Neurol

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In vivo time-lapse imaging of cell proliferation and differentiation in the optic tectum of Xenopus laevis tadpoles.

Publication Date: 2012 Feb 1 PMID: 22113462
Authors: Bestman, J. E. - Lee-Osbourne, J. - Cline, H. T.
Journal: J Comp Neurol

We analyzed the function of neural progenitors in the developing central nervous system of Xenopus laevis tadpoles by using in vivo time-lapse confocal microscopy to collect images through the tectum at intervals of 2-24 hours over 3 days. Neural progenitor cells were labeled with fluorescent protein reporters based on expression of endogenous Sox2 transcription factor. With this construct, we identified Sox2-expressing cells as radial glia and as a component of the progenitor pool of cells in the developing tectum that gives rise to neurons and other radial glia. Lineage analysis of individual radial glia and their progeny demonstrated that less than 10% of radial glia undergo symmetric divisions resulting in two radial glia, whereas the majority of radial glia divide asymmetrically to generate neurons and radial glia. Time-lapse imaging revealed the direct differentiation of radial glia into neurons. Although radial glia may guide axons as they navigate to the superficial tectum, we find no evidence that radial glia function as a scaffold for neuronal migration at early stages of tectal development. Over 3 days, the number of labeled cells increased 20%, as the fraction of radial glia dropped and the proportion of neuronal progeny increased to approximately 60% of the labeled cells. Tadpoles provided with short-term visual enhancement generated significantly more neurons, with a corresponding decrease in cell proliferation. Together these results demonstrate that radial glial cells are neural progenitors in the developing optic tectum and reveal that visual experience increases the proportion of neurons generated in an intact animal.

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Abdominal vagal afferent pathways and their distributions of intraganglionic laminar endings in the rat duodenum.

Publication Date: 2012 Apr 1 PMID: 22102316
Authors: Wang, F. B. - Young, Y. K. - Kao, C. K.
Journal: J Comp Neurol

We examined abdominal vagal afferents (n = 33) and the distributions of their intraganglionic laminar endings (IGLEs) in the duodenum. Rats (male, Sprague-Dawley) received a partial subdiaphragmatic vagotomy that spared a single branch. Wheat germ agglutinin-horseradish peroxidase (0.5-1.0 mul) was injected into the nodose ganglion ipsilateral to the vagotomized side. We observed that the hepatic branch does not project to the stomach, that the accessory celiac and celiac branches course along the celiac artery and innervate the intestines, and that the left nodose afferents innervate predominantly the duodenum. The hepatic branch innervates the duodenum via the "hepatoduodenal" subbranch and has the densest IGLE distribution in both the dorsoventral and the rostrocaudal extensions of the first 4-cm segment. Both gastric branches have two subbranches that innervate the duodenum; the "lesser curvature" subbranches follow the lesser curvature artery and may join the "hepatoduodenal" subbranch, whereas the "pyloric" subbranches run through the antrum and pylorus to reach the proximal duodenum. Moreover, the subbranches of ventral and dorsal gastric branches innervate more in the ventral and dorsal parts of the duodenum, respectively, and have more IGLEs in the rostral region than in the caudal. A posteriori comparisons indicate that, in the first-centimeter segment, the ventral gastric branch has significantly more IGLEs, whereas, in the third- and fourth-centimeter segments, the hepatic branch has more IGLEs. The finding that three different vagal branches innervate the duodenum with different densities of afferent endings might indicate a viscerotopic receptive field that coordinates digestive functions in feeding. J. Comp. Neurol. 520:1098-1113, 2012. (c) 2011 Wiley Periodicals, Inc.

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Rearrangement of the cone mosaic in the retina of the rat model of retinitis pigmentosa.

Publication Date: 2012 Mar 1 PMID: 22102145
Authors: Ji, Y. - Zhu, C. L. - Grzywacz, N. M. - Lee, E. J.
Journal: J Comp Neurol

In retinitis pigmentosa (RP), the death of cones normally follows some time after the degeneration of rods. Recently, surviving cones in RP have been studied and reported in detail. These cones undergo extensive remodeling in their morphology. Here we report an extension of the remodeling study to consider possible modifications of spatial-distribution patterns. For this purpose we used S334ter-line-3 transgenic rats, a transgenic model developed to express a rhodopsin mutation causing RP. In this study, retinas were collected at postnatal (P) days P5-30, 90, 180, and P600. We then immunostained the retinas to examine the morphology and distribution of cones and to quantify the total cone numbers. Our results indicate that cones undergo extensive changes in their spatial distribution to give rise to a mosaic comprising an orderly array of rings. These rings first begin to appear at P15 at random regions of the retina and become ubiquitous throughout the entire tissue by P90. Such distribution pattern loses its clarity by P180 and mostly disappears at P600, at which time the cones are almost all dead. In contrast, the numbers of cones in RP and normal conditions do not show significant differences at stages as late as P180. Therefore, rings do not form by cell death at their centers, but by cone migration. We discuss its possible mechanisms and suggest a role for hot spots of rod death and the remodeling of Muller cell process into zones of low density of photoreceptors. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Myoinhibitory peptides in the brain of the cockroach Leucophaea maderae and colocalization with pigment-dispersing factor in circadian pacemaker cells.

Publication Date: 2012 Apr 1 PMID: 22095637
Authors: Schulze, J. - Neupert, S. - Schmidt, L. - Predel, R. - Lamkemeyer, T. - Homberg, U. - Stengl, M.
Journal: J Comp Neurol

Myoinhibitory peptides (MIPs) are a family of insect W(X(6) )Wamides with inhibitory effects on visceral muscles and juvenile hormone synthesis. Although MIPs are widely distributed within the nervous system, a detailed analysis of their distribution and function in insect brains is still missing. We analyzed the distribution of MIPs in the brain of the cockroach Leucophaea maderae. We focused on the accessory medulla (AMe), a small neuropil near the medulla that acts as the master circadian clock. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and Nano-LC electrospray ionization (ESI) mass spectrometry revealed five Lem-MIPs in preparations of the AMe and corpora cardiaca. The complete sequences of two of these peptides were identified. Immunocytochemistry revealed wide distribution of MIP-related peptides in the cockroach brain. The superior median protocerebrum, parts of the central complex, and the tritocerebrum showed particularly dense immunostaining. In contrast, only a few local interneurons were stained in the antennal lobe and a few extrinsic neurons in the mushroom body, including a giant neuron innervating the calyces. The noduli of the AMe showed dense immunostaining, and neurons in all AMe cell groups except the anterior neurons were labeled. Pigment-dispersing factor- (PDF) and MIP immunostaining was colocalized in two neurons of the AMe. No colocalization of MIP- and PDF immunostaining was detected in the anterior optic commissure, but two small PDF-immunoreactive commissural fibers near the posterior optic commissure showed colocalized MIP immunostaining. The results suggest that several MIPs participate in different functional circuits of the circadian system and are involved in multiple brain circuits of the Madeira cockroach. J. Comp. Neurol. 520:1078-1097, 2012. (c) 2011 Wiley Periodicals, Inc.

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Development and distribution of neuronal cilia in mouse neocortex.

Publication Date: 2012 Mar 1 PMID: 22020803
Authors: Arellano, J. I. - Guadiana, S. M. - Breunig, J. J. - Rakic, P. - Sarkisian, M. R.
Journal: J Comp Neurol

Neuronal primary cilia are not generally recognized, but they are considered to extend from most, if not all, neurons in the neocortex. However, when and how cilia develop in neurons are not known. This study used immunohistochemistry for adenylyl cyclase III (ACIII), a marker of primary cilia, and electron microscopic analysis to describe the development and maturation of cilia in mouse neocortical neurons. Our results indicate that ciliogenesis is initiated in late fetal stages after neuroblast migration, when the mother centriole docks with the plasma membrane, becomes a basal body, and grows a cilia bud that we call a procilium. This procilium consists of a membranous protrusion extending from the basal body but lacking axonemal structure and remains undifferentiated until development of the axoneme and cilia elongation starts at about postnatal day 4. Neuronal cilia elongation and final cilia length depend on layer position, and the process extends for a long time, lasting 8-12 weeks. We show that, in addition to pyramidal neurons, inhibitory interneurons also grow cilia of comparable length, suggesting that cilia are indeed present in all neocortical neuron subtypes. Furthermore, the study of mice with defective ciliogenesis suggested that failed elongation of cilia is not essential for proper neuronal migration and laminar organization or establishment of neuronal polarity. Thus, the function of this organelle in neocortical neurons remains elusive. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Characterization of axo-axonic synapses in the piriform cortex of Mus musculus.

Publication Date: 2012 Mar 1 PMID: 22020781
Authors: Wang, X. - Sun, Q. Q.
Journal: J Comp Neurol

Previous anatomical and physiological studies have established major glutamatergic and GABAergic neuronal subtypes within the piriform cortical circuits. However, quantitative information regarding axo-axonic inhibitory synapses mediated by chandelier cells across major cortical subdivisions of piriform cortex is lacking. Therefore, we examined the properties of these synapses across the entire piriform cortex. Our results show the following. 1) gamma-Aminobutyric acid membrane transporter 1-positive varicosities, whose appearance resembles chandelier cartridges, are found around the initial segments of axons of glutamatergic cells across layers II and III. 2) Both the density of axo-axonic cartridges and the degree of gamma-aminobutyric acid membrane transporter 1 innervation in each axo-axonic synapse are significantly higher in the piriform cortex than in the neocortex. 3) Glutamate decarboxylase 67, vesicular GABA transporter, and parvalbumin, but not calbindin, are colocalized with the presynaptic varicosities, whereas gephyrin, Na-K-2Cl cotransporter 1, and GABA(A) receptor alpha1 subunit, but not K-Cl cotransporter 2, are colocalized at the presumed postsynaptic sites. 4) The axo-axonic cartridges innervate the majority of excitatory neurons and are distributed more frequently in putative centrifugal cells and posterior piriform cortex. We further describe the morphology of chandelier cells by using parvalbumin-immunoreactivity and single-cell labeling. In summary, our results demonstrate that a small population of chandelier cells mediates abundant axo-axonic synapses across the entire piriform cortex. Because of the critical location of these inhibitory synapses in relation to action potential regulation, our results highlight a critical role of axo-axonic synapses in regulating information flow and olfactory-related oscillations within the piriform cortex in vivo. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Coordinate development of skin cells and cutaneous sensory axons in zebrafish.

Publication Date: 2012 Mar 1 PMID: 22020759
Authors: O'Brien, G. S. - Rieger, S. - Wang, F. - Smolen, G. A. - Gonzalez, R. E. - Buchanan, J. - Sagasti, A.
Journal: J Comp Neurol

Peripheral sensory axons innervate the epidermis early in embryogenesis to detect touch stimuli. To characterize the time course of cutaneous innervation and the nature of interactions between sensory axons and skin cells at early developmental stages, we conducted a detailed analysis of cutaneous innervation in the head, trunk, and tail of zebrafish embryos and larvae from 18 to 78 hours postfertilization. This analysis combined live imaging of fish expressing transgenes that highlight sensory neurons and skin cells, transmission electron microscopy (TEM), and serial scanning electron microscopy (sSEM). In zebrafish, the skin initially consists of two epithelial layers, and all of the axons in the first wave of innervation are free endings. Maturation of the epithelium coincides with, but does not depend on, its innervation by peripheral sensory axons. We found that peripheral axons initially arborize between the two epithelial skin layers, but not within the basal lamina, as occurs in other organisms. Strikingly, as development proceeds, axons become tightly enveloped within basal keratinocytes, an arrangement suggesting that keratinocytes may serve structural or functional roles, akin to Schwann cells, in somatosensation mediated by these sensory neurons. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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The lateral hypothalamic parvalbumin-immunoreactive (PV1) nucleus in rodents.

Publication Date: 2012 Mar 1 PMID: 22020694
Authors: Meszar, Z. - Girard, F. - Saper, C. B. - Celio, M. R.
Journal: J Comp Neurol

In the lateral hypothalamus, groups of functionally related cells tend to be widely scattered rather than confined to discrete, anatomically distinct units. However, by using parvalbumin (PV)-specific antibodies, a solitary, compact cord of PV-immunoreactive cells (the PV1-nucleus) has been identified in the ventrolateral tuberal hypothalamus in various species. Here we describe the topography, the chemo-, cyto-, and myeloarchitectonics, and the ultrastructure of this PV1-nucleus in rodents. The PV1-nucleus is located within the ventrolateral division of the medial forebrain bundle. In the horizontal plane, it has a length of 1 mm in mice and 2 mm in rats. PV-immunoreactive perikarya fall into two distinct size categories and number ( approximately 800 in rats and approximately 400 in mice). They are intermingled with PV-negative neurons and coarse axons of the medial forebrain bundle, some of which are PV-positive. Symmetric and asymmetric synapses, as well as PV-positive and PV-negative fiber endings, terminate on the perikarya of both PV-positive and PV-negative neurons. PV-positive neurons of the PV1-nucleus express glutamate, not gamma-aminobutyric acid (GABA), the neurotransmitter that is usually associated with PV-containing nerve cells. Although we could not find evidence that PV1 neurons express either catecholamines or known neuropeptides, they sometimes are interspersed with the fibers and terminals of such cells. From its analogous topographical situation, the PV1-nucleus could correspond to the lateral tuberal nucleus in humans. We anticipate that the presence of the marker protein PV in the PV1-nucleus of the rodent hypothalamus will facilitate future studies relating to the connectivity, transcriptomics, and function of this entity. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Ontogeny of the cocaine- and amphetamine-regulated transcript (CART) neuropeptide system in the brain of zebrafish, Danio rerio.

Publication Date: 2012 Mar 1 PMID: 22009187
Authors: Mukherjee, A. - Subhedar, N. K. - Ghose, A.
Journal: J Comp Neurol

The cocaine- and amphetamine-regulated transcript (CART) peptidergic system is involved in processing diverse neuronal functions in adult animals, including energy metabolism. Although CART is widely distributed in the brain of a range of vertebrates, the ontogeny of this system has not been explored. The CART-immunoreactive system in the zebrafish central nervous system (CNS) was studied across developmental stages until adulthood. The peptide is expressed as early as 24 hours post fertilization and establishes itself in several discrete areas of the brain and spinal cord as development progresses. The trends in CART ontogeny suggest that it may be involved in the establishment of commissural tracts, typically expressing early but subsequently decaying. CART elements are commonly overrepresented in diverse sensory areas like the olfactory, photic, and acoustico-mechanosensory systems, perhaps indicating a role for the peptide in sensory perception. Key neuroendocrine centers, like the preoptic area, hypothalamus, and pituitary, conspicuously show CART innervations, suggesting functions analogous to those demonstrated in other chordates. Uniquely, the epiphysis also appears to employ CART as a neurotransmitter. The entopeduncular nucleus is a major CART-containing group in the adult teleost forebrain that may participate in glucose sensing. This region responds to glucose in the 15-day larvae, suggesting that the energy status sensing CART circuits is active early in development. The pattern of CART expression in zebrafish suggests conserved evolutionary trends among vertebrate species. Developmental expression profiling reveals putative novel functions and establishes zebrafish as a model to investigate CART function in physiology and development. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Segregation of visual inputs from different regions of the compound eye in two parallel pathways through the anterior optic tubercle of the bumblebee (Bombus ignitus).

Publication Date: 2012 Feb 1 PMID: 21953619
Authors: Pfeiffer, K. - Kinoshita, M.
Journal: J Comp Neurol

Visually guided behaviors require the brain to extract features of the visual world and to integrate them in a context-specific manner. Hymenopteran insects have been prime models for ethological research into visual behaviors for decades but knowledge about the underlying central processing is very limited. This is particularly the case for sky-compass navigation. To learn more about central processing of visual information in general and specifically to reveal a possible polarization vision pathway in the bee brain, we used tracer injections to investigate the pathways through the anterior optic tubercle, a prominent output target of the insect optic lobe, in the bumblebee Bombus ignitus. The anterior optic tubercle of the bumblebee is a small neuropil of 200 mum width and is located dorsolateral to the antennal lobe at the anterior surface of the brain. It is divided into a larger upper and a smaller lower subunit, both of which receive input from the optic lobe and connect to the lateral accessory lobe, and the contralateral tubercle, via two parallel pathways. The lower subunit receives input from the dorsal rim area (DRA) of the compound eye. The bumblebee DRA shares structural similarities with polarization-sensitive DRAs of other insects and looks similar to that of honeybees. We identified several neurons within this pathway that could be homologous to identified polarization-sensitive neurons in the locust brain. We therefore conclude that the pathway through the lower subunit of the anterior optic tubercle could carry polarization information from the periphery to the central brain.

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Differential sensitivity of specific neuronal populations of the rat hypothalamus to prolactin action.

Publication Date: 2012 Apr 1 PMID: 21953590
Authors: Sapsford, T. J. - Kokay, I. C. - Ostberg, L. - Bridges, R. S. - Grattan, D. R.
Journal: J Comp Neurol

Prolactin stimulates dopamine release from neuroendocrine dopaminergic (NEDA) neurons in the hypothalamic arcuate nucleus (ARC) to maintain low levels of serum prolactin. Elevated prolactin levels during pregnancy and lactation may mediate actions in other hypothalamic regions such as the paraventricular nucleus (PVN) and rostral preoptic area (rPOA). We predicted that NEDA neurons would be more sensitive prolactin targets than neurons in other regions because they are required to regulate basal prolactin secretion. Moreover, differences in the accessibility of the ARC to prolactin in blood may influence the responsiveness of this population. Therefore, we compared prolactin-induced signaling in different hypothalamic neuronal populations following either systemic or intracerebroventricular (icv) prolactin administration. Phosphorylation of the signal transduction factor, STAT5 (pSTAT5), was used to identify prolactin-responsive neurons. In response to systemic prolactin, pSTAT5-labeled cells were widely observed in the ARC but absent from the rPOA and PVN. Many of these responsive cells in the ARC were identified as NEDA neurons. The lowest icv prolactin dose (10 ng) induced pSTAT5 in the ARC, but with higher doses (>500 ng) pSTAT5 was detected in numerous regions, including the rPOA and PVN. NEDA neurons were maximally labeled with nuclear pSTAT5 in response to 500 ng prolactin and appeared to be more sensitive than dopaminergic neurons in the rPOA. Subpopulations of oxytocin neurons in the hypothalamus were also found to be differentially sensitive to prolactin. These data suggest that differences in the accessibility of the arcuate nucleus to prolactin, together with intrinsic differences in the NEDA neurons, may facilitate homeostatic feedback regulation of prolactin release. J. Comp. Neurol. 520:1062-1077, 2012. (c) 2011 Wiley Periodicals, Inc.

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Regional and subcellular distribution of the receptor-targeting protein PIST in the rat central nervous system.

Publication Date: 2012 Apr 1 PMID: 21953547
Authors: Chen, A. - Gobetaling, E. K. - Witkowski, L. - Bhindi, A. - Bauch, C. - Roussy, G. - Sarret, P. - Kreienkamp, H. J. - Stroh, T.
Journal: J Comp Neurol

Protein interacting specifically with Tc10, PIST, is a Golgi-associated sorting protein involved in regulating cell-surface targeting of plasma membrane receptors. The present study provides the first comprehensive description of PIST distribution in the mammalian central nervous system and of its subcellular localization by immunocytochemistry. PIST is distributed widely throughout the neuraxis, predominantly associated with neuronal cell bodies and dendrites. In hippocampal neurons, in vitro and in situ, PIST displayed a patchy subcellular distribution in an area surrounding the nucleus and extending into one of the major dendrites. By colocalization with the trans-Golgi marker TGN38, we were able to show that PIST is associated largely but not exclusively with the trans-Golgi network in central neurons. High or moderate to high levels of PIST-like immunoreactivity were found in cortical areas, in particular in layer V of the neocortex. The motor cortex was most strongly labeled. Also, the piriform and insular cortices displayed strong PIST labeling. In the hippocampus, CA2 but not CA1 or CA3 pyramidal cells displayed strong PIST-labeling, extending into their apical dendrites. In the thalamus, ventrolateral and laterodorsal nuclei were most strongly stained, whereas in the hypothalamus the supraoptic nucleus stood out with strong immunoreactivity. Strikingly, in the brainstem all cranial nerve motor nuclei were PIST-positive at varying levels, which is in keeping with the prominent expression of PIST in forebrain motor areas. This selective distribution of PIST suggests that the protein serves distinctive roles in specific neuronal populations, establishing functionally distinct zones, for instance, in the hippocampus. J. Comp. Neurol. 520:889-913, 2012. (c) 2011 Wiley Periodicals, Inc.

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Cone outer segment extracellular matrix as binding domain for interphotoreceptor retinoid-binding protein.

Publication Date: 2012 Mar 1 PMID: 21935947
Authors: Garlipp, M. A. - Nowak, K. R. - Gonzalez-Fernandez, F.
Journal: J Comp Neurol

Cones are critically dependent on interphotoreceptor retinoid-binding protein (IRBP) for retinoid delivery in the visual cycle. Cone-dominant vertebrates offer an opportunity to uncover the molecular basis of IRBP's role in this process. Here, we explore the association of IRBP with the interphotoreceptor matrix (IPM) of cones vs. rods in cone dominant retinas from chicken (Gallus domesticus), turkey (Meleagris gallopavo), and pig (Sus scrofa). Retinas were detached and fixed directly or washed in saline prior to fixation. Disassociated photoreceptors with adherent matrix were also prepared. Under 2 mM CaCl(2) , insoluble matrix was delaminated from saline washed retinas. The distribution of IRBP, as well as glycans binding peanut agglutinin (cone matrix) and wheat germ agglutinin (rod/cone matrix), was defined by confocal microscopy. Retina flat mounts showed IRBP diffusely distributed in an interconnecting, lattice-like pattern throughout the entire matrix. Saline wash replaced this pattern with fluorescent annuli surrounding individual cone outer segments. In isolated cones and matrix sheets, IRBP colocalized with the peanut agglutinin binding matrix glycans. Our results reveal a wash-resistant association of IRBP with a matrix domain immediately surrounding cone outer segments. The cone matrix sheath may be responsible for IRBP-mediated cone targeting of 11-cis retinoids. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Regeneration of olfactory afferent axons in the locust brain.

Publication Date: 2012 Mar 1 PMID: 21935945
Authors: Stern, M. - Scheiblich, H. - Eickhoff, R. - Didwischus, N. - Bicker, G.
Journal: J Comp Neurol

The insect olfactory system consists of thousands of sensory neurons on each antenna, which project into the primary olfactory center, the glomerular antennnal lobe. There, they form synapses with local interneurons and projection neurons, which relay olfactory information to the second-order olfactory center, the mushroom body. Olfactory afferents of adult locusts (Locusta migratoria) were axotomized by crushing the base of the antenna. We studied the resulting degeneration and regeneration in the antennal lobe by size measurements, anterograde dye labeling through the antennal nerve, and immunofluorescence staining of cell surface markers. Within 3 days postcrush, the antennal lobe size was reduced by 30% and from then onward regained size back to normal by 2 weeks postinjury. Concomitantly, anterograde labeling revealed regenerating afferents reaching the antennal lobe by day 4 postcrush, and reinnervating the olfactory neuropil almost back to normal within 2 weeks. Regenerated fibers were directed precisely into the antennal lobe, where they reinnervated glomeruli. As a remarkable exception, a few regenerating fibers projected erroneously into the mushroom body on a pathway that is normally chosen by second-order projection neurons. Regenerating afferents expressed the cell surface proteins lachesin and fasciclin I. The antennal lobe neuropil expressed the cell surface marker semaphorin 1a. In conclusion, axonal regeneration in the locust olfactory system appears to be possible, precise, and fast, opening the possibility of future functional and mechanistic studies. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Pre-Botzinger complex receives glutamatergic innervation from galaninergic and other retrotrapezoid nucleus neurons.

Publication Date: 2012 Apr 1 PMID: 21935944
Authors: Bochorishvili, G. - Stornetta, R. L. - Coates, M. B. - Guyenet, P. G.
Journal: J Comp Neurol

The retrotrapezoid nucleus (RTN) contains CO(2) -responsive neurons that regulate breathing frequency and amplitude. These neurons (RTN-Phox2b neurons) contain the transcription factor Phox2b, vesicular glutamate transporter 2 (VGLUT2) mRNA, and a subset contains preprogalanin mRNA. We wished to determine whether the terminals of RTN-Phox2b neurons contain galanin and VGLUT2 proteins, to identify the specific projections of the galaninergic subset, to test whether RTN-Phox2b neurons contact neurons in the pre-Botzinger complex, and to identify the ultrastructure of these synapses. The axonal projections of RTN-Phox2b neurons were traced by using biotinylated dextran amine (BDA), and many BDA-ir boutons were found to contain galanin immunoreactivity. RTN galaninergic neurons had ipsilateral projections that were identical with those of this nucleus at large: the ventral respiratory column, the caudolateral nucleus of the solitary tract, and the pontine Kolliker-Fuse, intertrigeminal region, and lateral parabrachial nucleus. For ultrastructural studies, RTN-Phox2b neurons (galaninergic and others) were transfected with a lentiviral vector that expresses mCherry almost exclusively in Phox2b-ir neurons. After spinal cord injections of a catecholamine neuron-selective toxin, there was a depletion of C1 neurons in the RTN area; thus it was determined that the mCherry-positive terminals located in the pre-Botzinger complex originated almost exclusively from the RTN-Phox2b (non-C1) neurons. These terminals were generally VGLUT2-immunoreactive and formed numerous close appositions with neurokinin-1 receptor-ir pre-Botzinger complex neurons. Their boutons (n = 48) formed asymmetric synapses filled with small clear vesicles. In summary, RTN-Phox2b neurons, including the galaninergic subset, selectively innervate the respiratory pattern generator plus a portion of the dorsolateral pons. RTN-Phox2b neurons establish classic excitatory glutamatergic synapses with pre-Botzinger complex neurons presumed to generate the respiratory rhythm. J. Comp. Neurol. 520:1047-1061, 2012. (c) 2011 Wiley Periodicals, Inc.

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Descending projections from the dysgranular zone of rat primary somatosensory cortex processing deep somatic input.

Publication Date: 2012 Apr 1 PMID: 21935942
Authors: Lee, T. - Kim, U.
Journal: J Comp Neurol

In the mammalian somatic system, peripheral inputs from cutaneous and deep receptors ascend via different subcortical channels and terminate in largely separate regions of the primary somatosensory cortex (SI). How these inputs are processed in SI and then projected back to the subcortical relay centers is critical for understanding how SI may regulate somatic information processing in the subcortex. Although it is now relatively well understood how SI cutaneous areas project to the subcortical structures, little is known about the descending projections from SI areas processing deep somatic input. We examined this issue by using the rodent somatic system as a model. In rat SI, deep somatic input is processed mainly in the dysgranular zone (DSZ) enclosed by the cutaneous barrel subfields. By using biotinylated dextran amine (BDA) as anterograde tracer, we characterized the topography of corticostriatal and corticofugal projections arising in the DSZ. The DSZ projections terminate mainly in the lateral subregions of the striatum that are also known as the target of certain SI cutaneous areas. This suggests that SI processing of deep and cutaneous information may be integrated, to a certain degree, in this striatal region. By contrast, at both thalamic and prethalamic levels as far as the spinal cord, descending projections from DSZ terminate in areas largely distinguishable from those that receive input from SI cutaneous areas. These subcortical targets of DSZ include not only the sensory but also motor-related structures, suggesting that SI processing of deep input may engage in regulating somatic and motor information flow between the cortex and periphery. J. Comp. Neurol. 520:1021-1046, 2012. (c) 2011 Wiley Periodicals, Inc.

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Distribution of type 1 cannabinoid receptor-expressing neurons in the septal-hypothalamic region of the mouse: Colocalization with GABAergic and glutamatergic markers.

Publication Date: 2012 Apr 1 PMID: 21935941
Authors: Hrabovszky, E. - Wittmann, G. - Kallo, I. - Fuzesi, T. - Fekete, C. - Liposits, Z.
Journal: J Comp Neurol

Type 1 cannabinoid receptor (CB1) is the principal mediator of retrograde endocannabinoid signaling in the brain. In this study, we addressed the topographic distribution and amino acid neurotransmitter phenotype of endocannabinoid-sensitive hypothalamic neurons in mice. The in situ hybridization detection of CB1 mRNA revealed high levels of expression in the medial septum (MS) and the diagonal band of Broca (DBB), moderate levels in the preoptic area and the hypothalamic lateroanterior (LA), paraventricular (Pa), ventromedial (VMH), lateral mammillary (LM), and ventral premammillary (PMV) nuclei, and low levels in many other hypothalamic regions including the suprachiasmatic (SCh) and arcuate (Arc) nuclei. This regional distribution pattern was compared with location of gamma-aminobutyric acid (GABA)ergic and glutamatergic cell groups, as identified by the expression of glutamic acid decarboxylase 65 (GAD65) and type 2 vesicular glutamate transporter (VGLUT2) mRNAs, respectively. The MS, DBB, and preoptic area showed overlaps between GABAergic and CB1-expressing neurons, whereas hypothalamic sites with moderate CB1 signals, including the LA, Pa, VMH, LM, and PMV, were dominated by glutamatergic neurons. Low CB1 mRNA levels were also present in other glutamatergic and GABAergic regions. Dual-label in situ hybridization experiments confirmed the cellular co-expression of CB1 with both glutamatergic and GABAergic markers. In this report we provide a detailed anatomical map of hypothalamic glutamatergic and GABAergic systems whose neurotransmitter release is controlled by retrograde endocannabinoid signaling from hypothalamic and extrahypothalamic target neurons. This neuroanatomical information contributes to an understanding of the role that the endocannabinoid system plays in the regulation of endocrine and metabolic functions. J. Comp. Neurol. 520:1005-1020, 2012. (c) 2011 Wiley Periodicals, Inc.

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Differential expression of Brn3 transcription factors in intrinsically photosensitive retinal ganglion cells in mouse.

Publication Date: 2012 Mar 1 PMID: 21935940
Authors: Jain, V. - Ravindran, E. - Dhingra, N. K.
Journal: J Comp Neurol

Several subtypes of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) have been reported. The M1 type of ipRGCs exhibit distinct properties compared with the remaining (non-M1) cells. They differ not only in their soma size and dendritic arbor, but also in their physiological properties, projection patterns, and functions. However, it is not known how these differences arise. We tested the hypothesis that M1 and non-M1 cells express Brn3 transcription factors differentially. The Brn3 family of class IV POU-domain transcription factors (Brn3a, Brn3b, and Brn3c) is involved in the regulation of differentiation, dendritic stratification, and axonal projection of retinal ganglion cells during development. By using double immunofluorescence for Brn3 transcription factors and melanopsin, and with elaborate morphometric analyses, we show in mouse retina that neither Brn3a nor Brn3c are expressed in ipRGCs. However, Brn3b is expressed in a subset of ipRGCs, particularly those with larger somas and lower melanopsin levels, suggesting that Brn3b is expressed preferentially in the non-M1 cells. By using dendritic stratification to distinguish M1 from non-M1 cells, we found that whereas nearly all non-M1 cells expressed Brn3b, a vast majority of the M1 cells were negative for Brn3b. Interestingly, in the small proportion of the M1 cells that did express Brn3b, the expression level of Brn3b was significantly lower than in the non-M1 cells. These results provide insights about how expression of specific molecules in a ganglion cell could be linked to its role in visual function. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Active zone density is conserved during synaptic growth but impaired in aged mice.

Publication Date: 2012 Feb 1 PMID: 21935939
Authors: Chen, J. - Mizushige, T. - Nishimune, H.
Journal: J Comp Neurol

Presynaptic active zones are essential structures for synaptic vesicle release, but the developmental regulation of their number and maintenance during aging at mammalian neuromuscular junctions (NMJs) remains unknown. Here, we analyzed the distribution of active zones in developing, mature, and aged mouse NMJs by immunohistochemical detection of the active zone-specific protein Bassoon. Bassoon is a cytosolic scaffolding protein essential for the active zone assembly in ribbon synapses and some brain synapses. Bassoon staining showed a punctate pattern in nerve terminals and axons at the nascent NMJ on embryonic days 16.5-18.5. Three-dimensional reconstruction of NMJs revealed that the majority of Bassoon puncta within an NMJ were attached to the presynaptic membrane from postnatal day 0 to adulthood, and colocalized with another active zone protein, Piccolo. During postnatal development, the number of Bassoon puncta increased as the size of the synapses increased. Importantly, the density of Bassoon puncta remained relatively constant from postnatal day 0 to 54 at 2.3 puncta/mum(2) , while the synapse size increased 3.3-fold. However, Bassoon puncta density and signal intensity were significantly attenuated at the NMJs of 27-month-old aged mice. These results suggest that synapses maintain the density of synaptic vesicle release sites while the synapse size changes, but this density becomes impaired during aging.

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Afferent and efferent projections of the mesopallium in the pigeon (Columba livia).

Publication Date: 2012 Mar 1 PMID: 21935938
Authors: Atoji, Y. - Wild, J. M.
Journal: J Comp Neurol

The mesopallium is a thick cell plate occupying a substantial portion of the avian dorsal pallium, but its hodology is incompletely known. In pigeons we examined fiber connections of the frontodorsal (MFD) and frontoventral mesopallium (MFV), the ventrolateral mesopallium (MVL), the lateral (MIVl) and medial (MIVm) parts of the intermediate ventral mesopallium, and the caudal mesopallium (MC). MFV, MIVl, and MC connect reciprocally with secondary centers of the trigeminal, tectofugal, and auditory systems, respectively. MVL forms reciprocal connections with both the entopallial core and belt. MFV, MIVl, MVL, and MC receive thalamic inputs different from those of primary sensory pallial regions and have reciprocal connections with the caudolateral nidopallium (NCL) or arcopallium. MIVm has a strong reciprocal connection with the intermediate medial nidopallium. It receives afferents from the visual Wulst, rostral MC, posterior dorsointermediate thalamic nucleus, and caudal part of the posterior dorsolateral thalamic nucleus, is connected reciprocally with the arcopallium, and projects to NCL. MFD has reciprocal connections with the medial frontal nidopallium, arcopallium, posterior pallial amygdala, dorsolateral corticoid area, and projects to the medial part of medial striatum and hypothalamus. These results indicate that six subdivisions of the mesopallium have strong connections with corresponding portions of the nidopallium. In particular, the sensory mesopallial components of MFV, MIVl, MVL, and MC form parallel pathways to the one-way sensory streams in the nidopallium and make either feedback or feedforward circuits to the secondary centers of the nidopallium. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Subdivisions of the turtle Pseudemys scripta hypothalamus based on the expression of regulatory genes and neuronal markers.

Publication Date: 2012 Feb 15 PMID: 21935937
Authors: Moreno, N. - Dominguez, L. - Morona, R. - Gonzalez, A.
Journal: J Comp Neurol

The patterns of distribution of a set of conserved brain developmental regulatory transcription factors and neuronal markers were analyzed in the hypothalamus of the juvenile turtle, Pseudemys scripta. Combined immunohistochemical techniques were used for the identification of the main boundaries and subdivisions in the optic, paraventricular, tuberal, and mammillary hypothalamic regions. The combination of Tbr1 and Pax6 with Nkx2.1 allowed identification of the boundary between the telencephalic preoptic area, rich in Nkx2.1 expression, and the prethalamic eminence, rich in Tbr1 expression. In addition, at this level Nkx2.2 expression defined the boundary between the telencephalon and the hypothalamus. The dorsalmost hypothalamic domain was the supraoptoparaventricular region that was defined by the expression of Otp/Pax6 and the lack of Nkx2.1/Isl1. It is subdivided into rostral, rich in Otp and Nkx2.2, and caudal, only Otp-positive, portions. Ventrally, the suprachiasmatic area was identified by its catecholaminergic groups and the lack of Otp, and could be further divided into a rostral portion, rich in Nkx2.1 and Nkx2.2, and a caudal portion, rich in Isl1 and devoid of Nkx2.1 expression. The expressions of Nkx2.1 and Isl1 defined the tuberal hypothalamus, whereas only the rostral portion expressed Otp. Its caudal boundary was evident by the lack of Isl1 in the adjacent mammillary area, which expressed Nkx2.1 and Otp. All these results provide an important set of data on the interpretation of the hypothalamic organization in a reptile, and hence make a useful contribution to the understanding of hypothalamic evolution.

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FoxP2 expression in the cerebellum and inferior olive: Development of the transverse stripe-shaped expression pattern in the mouse cerebellar cortex.

Publication Date: 2012 Feb 15 PMID: 21935935
Authors: Fujita, H. - Sugihara, I.
Journal: J Comp Neurol

Many molecules are expressed heterogeneously in subpopulations of cerebellar Purkinje cells (PCs) and inferior olive (IO) neurons during development or in adulthood. These expression patterns are often organized in longitudinal stripes in the cerebellar cortex, which may be related to functional compartmentalization. FoxP2, a transcription factor, is expressed in PCs and IO neurons, but the details of its expression pattern remain unclear. Here we examined FoxP2 expression patterns systematically by immunostaining serial sections of the hindbrain from embryonic day 14.5 to adulthood in mice. FoxP2 was highly expressed in virtually all PCs at and before postnatal day 6 (P6), except for those in the flocculus and small parts of the nodulus (vermal lobule X), where FoxP2 expression was moderate or absent. After P6, FoxP2 expression gradually diminished in PCs in some areas. In adults, FoxP2 was expressed, less intensely than in earlier stages, in subsets of PCs that were mostly arranged transversely along the folial apices. In contrast, FoxP2 was expressed intensely in most IO neurons during development and in adulthood. FoxP2 was also expressed in a small population of neurons in the cerebellar nuclei. FoxP2 expression in adult rats and chicks was generally comparable to that in adult mice, suggesting evolutionary conservation of the expression pattern. Thus, the FoxP2 expression pattern reflects new transverse compartmentalization in the adult cerebellar cortex, although its functional significance remains unclear.

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Subdivisions of the adult zebrafish subpallium by molecular marker analysis.

Publication Date: 2012 Feb 15 PMID: 21858823
Authors: Ganz, J. - Kaslin, J. - Freudenreich, D. - Machate, A. - Geffarth, M. - Brand, M.
Journal: J Comp Neurol

The morphology of the telencephalon displays great diversity among different vertebrate lineages. Particularly the everted telencephalon of ray-finned fishes shows a noticeably different morphology from the evaginated telencephalon of nonray-finned fishes and other vertebrates. This makes the comparison between the different parts of the telencephalon of ray-finned fishes and other vertebrates difficult. Based on neuroanatomical, neurochemical, and connectional data no consensus on the subdivisions of the adult telencephalon of ray-finned fishes and their relation to nuclei in the telencephalon of other vertebrates has been reached yet. For tetrapods, comparative expression pattern analysis of homologous developmental genes has been a successful approach to clarify homologies between different parts of the telencephalon. In the larval zebrafish, subdivisions of the subpallium have been proposed using conserved developmental gene expression. In this study, we investigate the subdivisions of the adult zebrafish telencephalon by analyzing the expression pattern of conserved molecular marker genes. We identify the boundary between the pallium and subpallium based on the complementary expression of dlx2a, dlx5a in the subpallium and tbr1, neurod in the pallium. Furthermore, combinatorial expression of Isl, nkx2.1b, lhx1b, tbr1, eomesa, emx1, emx2, and emx3 identifies striatal-like, pallidal-like, and septal-like subdivisions within the subpallium. In contrast to previous models, we propose that the striatum and pallidum are stretched along the rostrocaudal axis of the telencephalon. Further, the septal nuclei derive from both the pallium and subpallium. On this basis, we present a new model for the subdivisions of the subpallium in teleost fish.

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Sacral neural crest-derived cells enter the aganglionic colon of Ednrb-/- mice along extrinsic nerve fibers.

Publication Date: 2012 Feb 15 PMID: 21858821
Authors: Erickson, C. S. - Zaitoun, I. - Haberman, K. M. - Gosain, A. - Druckenbrod, N. R. - Epstein, M. L.
Journal: J Comp Neurol

Both vagal and sacral neural crest cells contribute to the enteric nervous system in the hindgut. Because it is difficult to visualize sacral crest cells independently of vagal crest, the nature and extent of the sacral crest contribution to the enteric nervous system are not well established in rodents. To overcome this problem we generated mice in which only the fluorescent protein-labeled sacral crest are present in the terminal colon. We found that sacral crest cells were associated with extrinsic nerve fibers. We investigated the source, time of appearance, and characteristics of the extrinsic nerve fibers found in the aganglionic colon. We observed that the pelvic ganglion neurons contributed a number of extrinsic fibers that travel within the hindgut between circular and longitudinal muscles and within the submucosa and serosa. Sacral crest-derived cells along these fibers diminished in number from fetal to postnatal stages. A small number of sacral crest-derived cells were found between the muscle layers and expressed the neuronal marker Hu. We conclude that sacral crest cells enter the hindgut by advancing on extrinsic fibers and, in aganglionic preparations, they form a small number of neurons at sites normally occupied by myenteric ganglia. We also examined the colons of ganglionated preparations and found sacral crest-derived cells associated with both extrinsic nerve fibers and nascent ganglia. Extrinsic nerve fibers serve as a route of entry for both rodent and avian sacral crest into the hindgut.

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Reelin demarcates a subset of pre-Botzinger complex neurons in adult rat.

Publication Date: 2012 Feb 15 PMID: 21858819
Authors: Tan, W. - Sherman, D. - Turesson, J. - Shao, X. M. - Janczewski, W. A. - Feldman, J. L.
Journal: J Comp Neurol

Identification of two markers of neurons in the pre-Botzinger complex (pre-BotC), the neurokinin 1 receptor (NK1R) and somatostatin (Sst) peptide, has been of great utility in understanding the essential role of the pre-BotC in breathing. Recently, the transcription factor dbx1 was identified as a critical, but transient, determinant of glutamatergic pre-BotC neurons. Here, to identify additional markers, we constructed and screened a single-cell subtractive cDNA library from pre-BotC inspiratory neurons. We identified the glycoprotein reelin as a potentially useful marker, because it is expressed in distinct populations of pre-BotC and inspiratory bulbospinal ventral respiratory group (ibsVRG) neurons. Reelin ibsVRG neurons were larger (27.1 +/- 3.8 mum in diameter) and located more caudally (>12.8 mm caudal to Bregma) than reelin pre-BotC neurons (15.5 +/- 2.4 mum in diameter, <12.8 mm rostral to Bregma). Pre-BotC reelin neurons coexpress NK1R and Sst. Reelin neurons were also found in the parahypoglossal and dorsal parafacial regions, pontine respiratory group, and ventromedial medulla. Reelin-deficient (Reeler) mice exhibited impaired respones to hypoxia compared with littermate controls. We suggest that reelin is a useful molecular marker for pre-BotC neurons in adult rodents and may play a functional role in pre-BotC microcircuits.

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Trigeminal and telencephalic projections to jaw and other upper vocal tract premotor neurons in songbirds: Sensorimotor circuitry for beak movements during singing.

Publication Date: 2012 Feb 15 PMID: 21858818
Authors: Wild, J. M. - Krutzfeldt, N. E.
Journal: J Comp Neurol

During singing in songbirds, the extent of beak opening, like the extent of mouth opening in human singers, is partially correlated with the fundamental frequency of the sounds emitted. Since song in songbirds is under the control of "the song system" (a collection of interconnected forebrain nuclei dedicated to the learning and production of song), it might be expected that beak movements during singing would also be controlled by this system. However, direct neural connections between the telencephalic output of the song system and beak muscle motor neurons in the brainstem are conspicuous by their absence, leaving unresolved the question of how beak movements are affected during singing. By using standard tract tracing methods, we sought to answer this question by defining beak premotor neurons and examining their afferent projections. In the caudal medulla, jaw premotor cell bodies were located adjacent to the terminal field of the output of the song system, into which many premotor neurons extended their dendrites. The premotor neurons also received a novel input from the trigeminal ganglion and an overlapping input from a lateral arcopallial component of a trigeminal sensorimotor circuit that traverses the forebrain. The ganglionic input in songbirds, which is not present in doves and pigeons that vocalize with a closed beak, may modulate the activity of beak premotor neurons in concert with the output of the song system. These inputs to jaw premotor neurons could, together, affect beak movements as a means of modulating filter properties of the upper vocal tract during singing.

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Adenosine A2A receptor in the monkey basal ganglia: Ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum.

Publication Date: 2012 Feb 15 PMID: 21858817
Authors: Bogenpohl, J. W. - Ritter, S. L. - Hall, R. A. - Smith, Y.
Journal: J Comp Neurol

The adenosine A(2A) receptor (A(2A) R) is a potential drug target for the treatment of Parkinson's disease and other neurological disorders. In rodents, the therapeutic efficacy of A(2A) R modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical substrate(s) through which these therapeutic benefits could be mediated, pre-embedding electron microscopy immunohistochemistry was used to conduct a detailed, quantitative ultrastructural analysis of A(2A) R localization in the primate basal ganglia and to assess the degree of A(2A) R/mGluR5 colocalization in the striatum. A(2A) R immunoreactivity was found at the highest levels in the striatum and external globus pallidus (GPe). However, the monkey, but not the rat, substantia nigra pars reticulata (SNr) also harbored a significant level of neuropil A(2A) R immunoreactivity. At the electron microscopic level, striatal A(2A) R labeling was most commonly localized in postsynaptic elements (58% +/- 3% of labeled elements), whereas, in the GPe and SNr, the labeling was mainly presynaptic (71% +/- 5%) or glial (27% +/- 6%). In both striatal and pallidal structures, putative inhibitory and excitatory terminals displayed A(2A) R immunoreactivity. Striatal A(2A) R/mGluR5 colocalization was commonly found; 60-70% of A(2A) R-immunoreactive dendrites or spines in the monkey striatum coexpress mGluR5. These findings provide the first detailed account of the ultrastructural localization of A(2A) R in the primate basal ganglia and demonstrate that A(2A) R and mGluR5 are located to interact functionally in dendrites and spines of striatal neurons. Together, these data foster a deeper understanding of the substrates through which A(2A) R could regulate primate basal ganglia function and potentially mediate its therapeutic effects in parkinsonism.

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Onecut 1 and Onecut 2 are potential regulators of mouse retinal development.

Publication Date: 2012 Apr 1 PMID: 21830221
Authors: Wu, F. - Sapkota, D. - Li, R. - Mu, X.
Journal: J Comp Neurol

Our current study focuses on the expression of two members of the onecut transcription factor family, Onecut1 (Oc1) and Onecut2 (Oc2), in the developing mouse retina. By immunofluorescence staining, we found that Oc1 and Oc2 had very similar expression patterns throughout retinal development. Both factors started to be expressed in the retina at around embryonic day (E) 11.5. At early stages (E11.5 and E12.5), they were expressed in both the neuroblast layer (NBL) and ganglion cell layer (GCL). As development progressed (from E14.5 to postnatal day [P] 0), expression diminished in the retinal progenitor cells and became more restricted to the GCL. By P5, Oc1 and Oc2 were expressed at very low levels in the GCL. By co-labeling with transcription factors known to be involved in retinal ganglion cell (RGC) development, we found that Oc1 and Oc2 had extensive overlap with Math5 in the NBL, and that they completely overlapped with Pou4f2 and Isl1 in the GCL, but only partially in the NBL. Co-labeling of Oc1 with cell cycle markers confirmed that Oc1 was expressed in both proliferating retinal progenitors and postmitotic retinal cells. In addition, we demonstrated that expression of Oc1 and Oc2 did not require Math5, Isl1, or Pou4f2. Thus, Oc1 and Oc2 may regulate the formation of RGCs in a pathway independent of Math5, Pou4f2, and Isl1. Furthermore, we showed that Oc1 and Oc2 were expressed in both developing and mature horizontal cells (HCs). Therefore the two factors may also function in the genesis and maintenance of HCs. J. Comp. Neurol. 520:952-969, 2012. (c) 2011 Wiley Periodicals, Inc.

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Plasticity of tyrosine hydroxylase and serotonergic systems in the regenerating spinal cord of adult zebrafish.

Publication Date: 2012 Apr 1 PMID: 21830219
Authors: Kuscha, V. - Barreiro-Iglesias, A. - Becker, C. G. - Becker, T.
Journal: J Comp Neurol

Monoaminergic innervation of the spinal cord has important modulatory functions for locomotion. Here we performed a quantitative study to determine the plastic changes of tyrosine hydroxylase-positive (TH1(+) ; mainly dopaminergic), and serotonergic (5-HT(+) ) terminals and cells during successful spinal cord regeneration in adult zebrafish. TH1(+) innervation in the spinal cord is derived from the brain. After spinal cord transection, TH1(+) immunoreactivity is completely lost from the caudal spinal cord. Terminal varicosities increase in density rostral to the lesion site compared with unlesioned controls and are re-established in the caudal spinal cord at 6 weeks post lesion. Interestingly, axons mostly fail to re-innervate more caudal levels of the spinal cord even after prolonged survival times. However, densities of terminal varicosities correlate with recovery of swimming behavior, which is completely lost again after re-lesion of the spinal cord. Similar observations were made for terminals derived from descending 5-HT(+) axons from the brain. In addition, spinal 5-HT(+) neurons were newly generated after a lesion and transiently increased in number up to fivefold, which depended in part on hedgehog signaling. Overall, TH1(+) and 5-HT(+) innervation is massively altered in the successfully regenerated spinal cord of adult zebrafish. Despite these changes in TH and 5-HT systems, a remarkable recovery of swimming capability is achieved, suggesting significant plasticity of the adult spinal network during regeneration. J. Comp. Neurol. 520:933-951, 2012. (c) 2011 Wiley Periodicals, Inc.

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Retinal input influences the size and corticocortical connectivity of visual cortex during postnatal development in the ferret.

Publication Date: 2012 Apr 1 PMID: 21830218
Authors: Bock, A. S. - Kroenke, C. D. - Taber, E. N. - Olavarria, J. F.
Journal: J Comp Neurol

Retinal input plays an important role in the specification of topographically organized circuits and neuronal response properties, but the mechanism and timing of this effect is not known in most species. A system that shows dramatic dependence on retinal influences is the interhemispheric connection through the corpus callosum. Using ferrets, we analyzed the extent to which development of the visual callosal pattern depends on retinal influences, and explored the period during which these influences are required for normal pattern formation. We studied the mature callosal patterns in normal ferrets and in ferrets bilaterally enucleated (BE) at postnatal day 7 (P7) or P20. Callosal patterns were revealed in tangential sections from unfolded and flattened brains following multiple injections of horseradish peroxidase in the opposite hemisphere. We also estimated the effect of enucleation on the surface areas of striate and extrastriate visual cortex by using magnetic resonance imaging (MRI) data from intact brains. In BEP7 ferrets we found that the pattern of callosal connections was highly anomalous and the sizes of both striate and extrastriate visual cortex were significantly reduced. In contrast, enucleation at P20 had no significant effect on the callosal pattern, but it still caused a reduction in the size of striate and extrastriate visual cortex. Finally, retinal deafferentation had no significant effect on the number of visual callosal neurons. These results indicate that the critical period during which the eyes influence the development of callosal patterns, but not the size of visual cortex, ends by P20 in the ferret. J. Comp. Neurol. 520:914-932, 2012. (c) 2011 Wiley Periodicals, Inc.

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Parallel feedback pathways in visual cortex of cats revealed through a modified rabies virus.

Publication Date: 2012 Apr 1 PMID: 21826663
Authors: Connolly, J. D. - Hashemi-Nezhad, M. - Lyon, D. C.
Journal: J Comp Neurol

The visual cortex of cats is highly evolved. Analogously to the brains of primates, large numbers of visual areas are arranged hierarchically and can be parsed into separate dorsal and ventral streams for object recognition and visuospatial representation. Within early primate visual areas, V1 and V2, and to a lesser extent V3, the two streams are relatively segregated and relayed in parallel to higher order cortex, although there is some evidence suggesting an alignment of V2 and V3 to one stream over the other. For cats, there is no evidence of anatomical segregation in areas 18 and 19, the analogs to V2 and V3. However, previous work was only qualitative in nature. Here we re-examined the feedback connectivity patterns of areas 18/19 in quantitative detail. To accomplish this, we used a genetically modified rabies virus that acts as a retrograde tracer and fills neurons with fluorescent protein. After injections into area 19, many more neurons were labeled in putative ventral stream area 21a than in putative dorsal stream region posterolateral suprasylvian complex of areas (PLS), and the dendrites of neurons in 21a were significantly more complex. Conversely, area 18 injections labeled more neurons in PLS, and these were more complex than neurons in 21a. We infer from our results that area 19 in cat is more aligned to the ventral stream and area 18 to the dorsal stream. Based on the success of our approach, we suggest that this method could be applied to resolve similar issues related to primate V3. J. Comp. Neurol. 520:988-1004, 2012. (c) 2011 Wiley Periodicals, Inc.

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Structural organization of the presynaptic density at identified synapses in the locust central nervous system.

Publication Date: 2012 Feb 1 PMID: 21826661
Authors: Leitinger, G. - Masich, S. - Neumuller, J. - Pabst, M. A. - Pavelka, M. - Rind, F. C. - Shupliakov, O. - Simmons, P. J. - Kolb, D.
Journal: J Comp Neurol

In a synaptic active zone, vesicles aggregate around a densely staining structure called the presynaptic density. We focus on its three-dimensional architecture and a major molecular component in the locust. We used electron tomography to study the presynaptic density in synapses made in the brain by identified second-order neuron of the ocelli. Here, vesicles close to the active zone are organized in two rows on either side of the presynaptic density, a level of organization not previously reported in insect central synapses. The row of vesicles that is closest to the density's base includes vesicles docked with the presynaptic membrane and thus presumably ready for release, whereas the outer row of vesicles does not include any that are docked. We show that a locust ortholog of the Drosophila protein Bruchpilot is localized to the presynaptic density, both in the ocellar pathway and compound eye visual neurons. An antibody recognizing the C-terminus of the Bruchpilot ortholog selectively labels filamentous extensions of the presynaptic density that reach out toward vesicles. Previous studies on Bruchpilot have focused on its role in neuromuscular junctions in Drosophila, and our study shows it is also a major functional component of presynaptic densities in the central nervous system of an evolutionarily distant insect. Our study thus reveals Bruchpilot executes similar functions in synapses that can sustain transmission of small graded potentials as well as those relaying large, spike-evoked signals.

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Toward a single-cell-based analysis of neuropeptide expression in Periplaneta americana antennal lobe neurons.

Publication Date: 2012 Mar 1 PMID: 21826660
Authors: Neupert, S. - Fusca, D. - Schachtner, J. - Kloppenburg, P. - Predel, R.
Journal: J Comp Neurol

A multitude of potential neurotransmitters and neuromodulators, including peptides, have been detected in the antennal lobe (AL), the first synaptic relay of the central olfactory pathway in the insect brain. However, the functional role of neuropeptides in this system has yet to be revealed. An important prerequisite to understanding the role of neuropeptides is to match the functionally different cell types in the AL with their peptide profiles by using electrophysiological recordings combined with immunocytochemical studies and/or single-cell mass spectrometry. The olfactory system of Periplaneta americana is particularly well suited to accomplish this goal because several physiologically distinct neuron types can be unequivocally identified. With the aim to analyze the neuropeptide inventory of the P. americana AL, this study is an essential step in this direction. First, we systematically analyzed different parts of the AL by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry to obtain the complete set of neuropeptides present. Altogether, 56 ion signals could be assigned to products of 10 neuropeptide genes (allatostatins A, B, C, SIFamide, allatotropin, FMRFamide-related peptides [myosuppressin, short neuropeptides F, extended FMRFamides], crustacean cardioactive peptide, tachykinin-related peptides). In a second step, a combination of immunocytochemistry and mass spectrometric profiling of defined AL compartments was used to reveal the spatial distribution of neuropeptide-containing cells. Finally, we demonstrated the feasibility of MALDI-TOF mass spectrometric profiling of single AL neurons, which is an important precondition for combining electrophysiology with peptide profiling at the single-cell level. J. Comp. Neurol., 2012. (c) 2011 Wiley Periodicals, Inc.

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Neuropeptide F immunoreactive clock neurons modify evening locomotor activity and free-running period in Drosophila melanogaster.

Publication Date: 2012 Apr 1 PMID: 21826659
Authors: Hermann, C. - Yoshii, T. - Dusik, V. - Helfrich-Forster, C.
Journal: J Comp Neurol

Different subsets of Drosophila melanogaster's clock neurons are characterized by their specific functions in daily locomotor rhythms and the differences in their neurotransmitter composition. We investigated the function of the neuropeptide F (NPF) immunoreactive clock neurons in the rhythmic locomotor behavior of adult flies. We newly identified the fifth s-LN(v) and a subset of the l-LN(v) s as NPF-positive in addition to the three LN(d) s that have been described previously. We then selectively ablated different subsets of NPF-expressing neurons using npfGal4-targeted expression of the cell death gene head involution defective (hid) in combination with cryGal80 and pdfGal80. By analyzing daily locomotor rhythms in these flies, we show that the NPF-positive clock neurons-especially the fifth s-LN(v) and the LN(d) s-are involved in both the control of the free-running period in constant darkness (DD) and the phasing and amplitude of the evening activity in light-dark (LD) cycles. Furthermore, we show that the simultaneous ablation of NPF and pigment dispersing factor (PDF)-immunoreactive neurons has additive effects in LD, resulting in an evening peak phase that is even more advanced in comparison to PDF-ablated flies. We also found that this more advanced evening peak is additionally reduced in amplitude. To putatively assign the observed phenotypes to the action of NPF, we knocked it down in conjunction with PDF using RNA-interference (RNAi) and further suggest a possible role for NPF in the control of the flies' evening activity. J. Comp. Neurol. 520:970-987, 2012. (c) 2011 Wiley Periodicals, Inc.

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Cortical and subcortical connections of V1 and V2 in early postnatal macaque monkeys.

Publication Date: 2012 Feb 15 PMID: 21800316
Authors: Baldwin, M. K. - Kaskan, P. M. - Zhang, B. - Chino, Y. M. - Kaas, J. H.
Journal: J Comp Neurol

Connections of primary (V1) and secondary (V2) visual areas were revealed in macaque monkeys ranging in age from 2 to 16 weeks by injecting small amounts of cholera toxin subunit B (CTB). Cortex was flattened and cut parallel to the surface to reveal injection sites, patterns of labeled cells, and patterns of cytochrome oxidase (CO) staining. Projections from the lateral geniculate nucleus and pulvinar to V1 were present at 4 weeks of age, as were pulvinar projections to thin and thick CO stripes in V2. Injections into V1 in 4- and 8-week-old monkeys labeled neurons in V2, V3, middle temporal area (MT), and dorsolateral area (DL)/V4. Within V1 and V2, labeled neurons were densely distributed around the injection sites, but formed patches at distances away from injection sites. Injections into V2 labeled neurons in V1, V3, DL/V4, and MT of monkeys 2-, 4-, and 8-weeks of age. Injections in thin stripes of V2 preferentially labeled neurons in other V2 thin stripes and neurons in the CO blob regions of V1. A likely thick stripe injection in V2 at 4 weeks of age labeled neurons around blobs. Most labeled neurons in V1 were in superficial cortical layers after V2 injections, and in deep layers of other areas. Although these features of adult V1 and V2 connectivity were in place as early as 2 postnatal weeks, labeled cells in V1 and V2 became more restricted to preferred CO compartments after 2 weeks of age.

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Histamine receptors of cones and horizontal cells in Old World monkey retinas.

Publication Date: 2012 Feb 15 PMID: 21800315
Authors: Vila, A. - Satoh, H. - Rangel, C. - Mills, S. L. - Hoshi, H. - O'Brien, J. - Marshak, D. R. - Macleish, P. R. - Marshak, D. W.
Journal: J Comp Neurol

In primates the retina receives input from histaminergic neurons in the posterior hypothalamus that are active during the day. In order to understand how this input contributes to information processing in Old World monkey retinas, we have been localizing histamine receptors (HR) and studying the effects of histamine on the neurons that express them. Previously, we localized HR3 to the tips of ON bipolar cell dendrites and showed that histamine hyperpolarizes the cells via this receptor. We raised antisera against synthetic peptides corresponding to an extracellular domain of HR1 between the 4th and 5th transmembrane domains and to an intracellular domain near the carboxyl terminus of HR2. Using these, we localized HR1 to horizontal cells and a small number of amacrine cells and localized HR2 to puncta closely associated with synaptic ribbons inside cone pedicles. Consistent with this, HR1 mRNA was detected in horizontal cell perikarya and primary dendrites and HR2 mRNA was found in cone inner segments. We studied the effect of 5 muM exogenous histamine on primate cones in macaque retinal slices. Histamine reduced I(h) at moderately hyperpolarized potentials, but not the maximal current. This would be expected to increase the operating range of cones and conserve ATP in bright, ambient light. Thus, all three major targets of histamine are in the outer plexiform layer, but the retinopetal axons containing histamine terminate in the inner plexiform layer. Taken together, the findings in these three studies suggest that histamine acts primarily via volume transmission in primate retina.

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Cellular, biochemical, and molecular characterization of nitric oxide synthase expressed in the nervous system of the prosobranch Stramonita haemastoma (Gastropoda, Neogastropoda).

Publication Date: 2012 Feb 1 PMID: 21800313
Authors: Cioni, C. - Di Patti, M. C. - Venturini, G. - Modica, M. V. - Scarpa, F. - Oliverio, M. - Toni, M.
Journal: J Comp Neurol

Nitric oxide synthase (NOS) has been characterized in several opistobranchs and pulmonates but it was much less investigated in prosobranchs, which include more than 20,000 species and account for most of the gastropod diversity. Therefore, new data from this large group are needed for a better knowledge of the molecular evolution of NOS enzymes in molluscs. This study focused on NOS expressed in the nervous system of the prosobranch neogastropod Stramonita haemastoma. In this study we report compelling evidence on the expression of a constitutive Ca(2+) /CaM-dependent neuronal NOS in the central and peripheral nervous system. The prevailing neuronal localization of NADPHd activity was demonstrated by NADPHd histochemistry in both central and peripheral nervous system structures. L-arginine/citrulline assays suggested that Stramonita NOS is a constitutive enzyme which is both cytosolic and membrane-bound. Molecular cloning of the full-length Stramonita NOS (Sh-NOS) by reverse-transcription polymerase chain reaction (RT-PCR) followed by 5' and 3' RACE showed that Sh-NOS is a protein of 1,517 amino acids, containing a PDZ domain at the N-terminus and sharing similar regulatory domains to the mammalian neuronal NOS (nNOS). Regional expression of the Sh-NOS gene was evaluated by RT-PCR. This analysis showed different expression levels in the nerve ring, the osphradium, the cephalic tentacles, the buccal tissues, and the foot, whereas NOS expression was not found in the salivary glands and the gland of Leiblein. The present data provide a solid background for further studies addressing the specific functions of NO in neogastropods.

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A survey of oral cavity afferents to the rat nucleus tractus solitarii.

Publication Date: 2012 Feb 15 PMID: 21800298
Authors: Corson, J. - Aldridge, A. - Wilmoth, K. - Erisir, A.
Journal: J Comp Neurol

Visualization of myelinated fiber arrangements, cytoarchitecture, and projection fields of afferent fibers in tandem revealed input target selectivity in identified subdivisions of the nucleus tractus solitarii (NTS). The central fibers of the chorda tympani (CT), greater superficial petrosal nerve (GSP), and glossopharyngeal nerve (IX), three nerves that innervate taste buds in the oral cavity, prominently occupy the gustatory-sensitive rostrocentral subdivision. In addition, CT and IX innervate and overlap in the rostrolateral subdivision, which is primarily targeted by the lingual branch of the trigeminal nerve (LV). In the rostrocentral subdivision, compared with the CT terminal field, GSP appeared more rostral and medial, and IX was more dorsal and caudal. Whereas IX and LV filled the rostrolateral subdivision diffusely, CT projected only to the dorsal and medial portions. The intermediate lateral subdivision received input from IX and LV but not CT or GSP. In the caudal NTS, the ventrolateral subdivision received notable innervation from CT, GSP, and LV, but not IX. No caudal subnuclei medial to the solitary tract contained labeled afferent fibers. The data indicate selectivity of fiber populations within each nerve for functionally distinct subdivisions of the NTS, highlighting the possibility of equally distinct functions for CT in the rostrolateral NTS, and CT and GSP in the caudal NTS. Further, this provides a useful anatomical template to study the role of oral cavity afferents in the taste-responsive subdivision of the NTS as well as in subdivisions that regulate ingestion and other oromotor behaviors.

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Expression analysis of the regenerating gene (Reg) family members Reg-IIIbeta and Reg-IIIgamma in the mouse during development.

Publication Date: 2012 Feb 15 PMID: 21681751
Authors: Matsumoto, S. - Konishi, H. - Maeda, R. - Kiryu-Seo, S. - Kiyama, H.
Journal: J Comp Neurol

The regenerating gene/regenerating islet-derived (Reg) family is a group of small secretory proteins. Within this family, Reg type-III (Reg-III) consists of: Reg-IIIalpha, -beta, -gamma, and -delta. To elucidate the physiological relevance of Reg-III, we examined the localization and ontogeny of Reg-IIIbeta and Reg-IIIgamma in mice at different time points spanning from embryonic day 13.5 to 7 weeks old, using in situ hybridization and immunohistochemistry. Our results showed that Reg-IIIbeta was expressed in specific subsets of primary sensory neurons and motor neurons, and that expression was transient during the embryonic and perinatal periods. Reg-IIIbeta expression was also observed in absorptive epithelial cells of the intestine. In contrast, Reg-IIIgamma expression was mainly observed in epithelial cells of the airways and intestine, but not in the nervous system, and expression levels showed a gradually increasing pattern along with development. In the airways Reg-IIIgamma was expressed in goblet and Clara-like cells, whereas in the intestine Reg-IIIgamma was expressed in the absorptive epithelial cells and Paneth cells, and was found to be expressed in development before these organs had been exposed to the outside world. The present findings imply that Reg-IIIbeta and Reg-IIIgamma expression is regulated along divergent pathways. Furthermore, we also suggest that expression of Reg-IIIgamma in the airway and intestinal epithelia may occur to protect these organs from exposure to antigens or other factors (e.g., microbes) in the outer world, whereas the transient expression of Reg-IIIbeta in the nervous system may be associated with the development of the peripheral nervous system including such processes as myelination.

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Characterization of the bed nucleus of the stria terminalis in the forebrain of anuran amphibians.

Publication Date: 2012 Feb 1 PMID: 21674496
Authors: Moreno, N. - Morona, R. - Lopez, J. M. - Dominguez, L. - Joven, A. - Bandin, S. - Gonzalez, A.
Journal: J Comp Neurol

Major common features have been reported for the organization of the basal telencephalon in amniotes, and most characteristics were thought to be acquired in the transition from anamniotes to amniotes. However, gene expression, neurochemical, and hodological data obtained for the basal ganglia and septal and amygdaloid complexes in amphibians (anamniotic tetrapods) have strengthened the idea of a conserved organization in tetrapods. A poorly characterized region in the forebrain of amniotes has been the bed nucleus of the stria terminalis (BST), but numerous recent investigations have characterized it as a member of the extended amygdala. Our study analyzes the main features of the BST in anuran amphibians to establish putative homologies with amniotes. Gene expression patterns during development identified the anuran BST as a subpallial, nonstriatal territory. The BST shows Nkx2.1 and Lhx7 expression and contains an Islet1-positive cell subpopulation derived from the lateral ganglionic eminence. Immunohistochemistry for diverse peptides and neurotransmitters revealed that the distinct chemoarchitecture of the BST is strongly conserved among tetrapods. In vitro tracing techniques with dextran amines revealed important connections between the BST and the central and medial amygdala, septal territories, medial pallium, preoptic area, lateral hypothalamus, thalamus, and prethalamus. The BST receives dopaminergic projections from the ventral tegmental area and is connected with the laterodorsal tegmental nucleus and the rostral raphe in the brainstem. All these data suggest that the anuran BST shares many features with its counterpart in amniotes and belongs to a basal continuum, likely controlling similar reflexes, reponses, and behaviors in tetrapods.

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Organization of the serotonergic innervation of the feeding (buccal) musculature during the maturation of the pond snail Lymnaea stagnalis: a morphological and biochemical study.

Publication Date: 2012 Feb 1 PMID: 21674495
Authors: Balog, G. - Voronezhskaya, E. E. - Hiripi, L. - Elekes, K.
Journal: J Comp Neurol

The serotonergic innervation of the buccal musculature responsible for feeding (radula protraction) was investigated during the maturation of the pond snail, Lymnaea stagnalis L., applying light and electron microscopic immunohistochemistry and biochemical approaches. According to epifluorescence and laser confocal microscopy, the first 5-HT-like-immunoreactive (5-HTLIR) processes appeared on the surface of the musculature at the postmetamorphic E80% embryonic stage. Until hatching, the innervation continued to increase in density, showing axon arborizations with projections into the deeper muscle levels. An adult-like pattern of 5-HTLIR innervation appeared at P2-P3 juvenile stages. At the ultrastructural level, close (16-20 nm) but mostly unspecialized neuromuscular contacts were formed by both unlabeled and 5-HTLIR axon profiles from the E80% embryonic stage. Labeled processes were also found located relatively far from the muscle cells. An HPLC assay showed a gradual increase of the 5-HT level in the buccal mass during development. The buccal mass was characterized by a single-component high-affinity 5-HT uptake system, and 5-HT release could be evoked by 100 mM K(+) and blocked in Ca(2+) -free medium. It is suggested that 5-HT plays a wide modulatory role in the peripheral feeding system and is also involved in the functional maturation of the muscle system.

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Stability of presynaptic vesicle pools and changes in synapse morphology in the amygdala following fear learning in adult rats.

Publication Date: 2012 Feb 1 PMID: 21674493
Authors: Ostroff, L. E. - Cain, C. K. - Jindal, N. - Dar, N. - Ledoux, J. E.
Journal: J Comp Neurol

Changes in synaptic strength in the lateral amygdala (LA) that occur with fear learning are believed to mediate memory storage, and both presynaptic and postsynaptic mechanisms have been proposed to contribute. In a previous study we used serial section transmission electron microscopy (ssTEM) to observe differences in dendritic spine morphology in the adult rat LA after fear conditioning, conditioned inhibition (safety conditioning), or naive control handling (Ostroff et al. [2010] Proc Natl Acad Sci U S A 107:9418-9423). We have now reconstructed axons from the same dataset and compared their morphology and relationship to the postsynaptic spines between the three training groups. Relative to the naive control and conditioned inhibition groups, the ratio of postsynaptic density (PSD) area to docked vesicles at synapses was greater in the fear-conditioned group, while the size of the synaptic vesicle pools was unchanged. There was significant coherence in synapse size between neighboring boutons on the same axon in the naive control and conditioned inhibition groups, but not in the fear-conditioned group. Within multiple-synapse boutons, both synapse size and the PSD-to-docked vesicle ratio were variable between individual synapses. Our results confirm that synaptic connectivity increases in the LA with fear conditioning. In addition, we provide evidence that boutons along the same axon and even synapses on the same bouton are independent in their structure and learning-related morphological plasticity.

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Functional implications of limited leptin receptor and ghrelin receptor coexpression in the brain.

Publication Date: 2012 Feb 1 PMID: 21674492
Authors: Perello, M. - Scott, M. M. - Sakata, I. - Lee, C. E. - Chuang, J. C. - Osborne-Lawrence, S. - Rovinsky, S. A. - Elmquist, J. K. - Zigman, J. M.
Journal: J Comp Neurol

The hormones leptin and ghrelin act in apposition to one another in the regulation of body weight homeostasis. Interestingly, both leptin receptor expression and ghrelin receptor expression have been observed within many of the same nuclei of the central nervous system (CNS), suggesting that these hormones may act on a common population of neurons to produce changes in food intake and energy expenditure. In the present study we explored the extent of this putative direct leptin and ghrelin interaction in the CNS and addressed the question of whether a loss of ghrelin signaling would affect sensitivity to leptin. Using histological mapping of leptin receptor and ghrelin receptor expression, we found that cells containing both leptin receptors and ghrelin receptors are mainly located in the medial part of the hypothalamic arcuate nucleus. In contrast, coexpression was much less extensive elsewhere in the brain. To assess the functional consequences of this observed receptor distribution, we explored the effect of ghrelin receptor deletion on leptin sensitivity. In particular, the responses of ad libitum-fed, diet-induced obese and fasted mice to the anorectic actions of leptin were examined. Surprisingly, we found that deletion of the ghrelin receptor did not affect the sensitivity to exogenously administrated leptin. Thus, we conclude that ghrelin and leptin act largely on distinct neuronal populations and that ghrelin receptor deficiency does not affect sensitivity to the anorexigenic and body weight-lowering actions of leptin.

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Peroxiredoxin distribution in the mouse brain with emphasis on neuronal populations affected in neurodegenerative disorders.

Publication Date: 2012 Feb 1 PMID: 21674491
Authors: Goemaere, J. - Knoops, B.
Journal: J Comp Neurol

Redox changes are observed in neurodegenerative diseases, ranging from increased levels of reactive oxygen/nitrogen species and disturbance of antioxidant systems, to nitro-oxidative damage. By reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides, peroxiredoxins (Prdxs) represent a major potential protective barrier against nitro-oxidative insults in the brain. While recent works have investigated the putative role of Prdxs in neurodegenerative disorders, less is known about their expression in the healthy brain. Here we used immunohistochemistry to map basal expression of Prdxs throughout C57BL/6 mouse brain. We first confirmed the neuronal localization of Prdx2-5 and the glial expression of Prdx1, Prdx4, and Prdx6. Then we performed an in-depth analysis of neuronal Prdx distribution in the brain. Our results show that Prdx2-5 are widely detected in the different neuronal populations, and especially well expressed in the olfactory bulb, in the cerebral cortex, in pons nuclei, in the red nucleus, in all cranial nerve nuclei, in the cerebellum, and in motor neurons of the spinal cord. In contrast, Prdx expression is very low in the dopaminergic neurons of substantia nigra pars compacta and in the CA1/2 pyramidal cells of hippocampus. This low basal expression may contribute to the vulnerability of these neurons to nitro-oxidative attacks occurring in Parkinson's disease and Alzheimer's disease. In addition, we found that Prdx expression levels are unevenly distributed among neurons of a determined region and that distinct regional patterns of expression are observed between isoforms, reinforcing the hypothesis of the nonredundant function of Prdxs.

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Motoneurons, DUM cells, and sensory neurons in an insect thoracic ganglion: a tracing study in the stick insect Carausius morosus.

Publication Date: 2012 Feb 1 PMID: 21618233
Authors: Goldammer, J. - Buschges, A. - Schmidt, J.
Journal: J Comp Neurol

Anatomical features of leg motoneurons, dorsal unpaired median (DUM) cells, and sensory neurons in stick insect mesothoracic ganglia were examined using fluorescent dye backfills of lateral nerves. Structures were analyzed in whole-mounts of ganglia and transverse sections. Numbers of motoneurons and details of their structure by far exceed previously published data. The general neuroanatomical layout of motoneurons matches the general orthopteran pattern. Cell bodies of excitatory motoneurons form clusters in the lateral cortex, dendrites branch mainly in the dorsal neuropil. We identified nine DUM cells, six of which have axons in nerve nl5. Most sensory fibers terminate in the ventral association center (VAC). Twenty-three small cell bodies located close to the soma of the fast extensor tibiae motoneuron likely belong to strand receptors. Labeled structures are compared with previously published data from stick insects and other orthopterous insects.

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