Neuron

Value representations in the primate striatum during matching behavior.

Publication Date: 2008 May 8 PMID: 18466754
Authors: Lau, B. - Glimcher, P. W.
Journal: Neuron

Choosing the most valuable course of action requires knowing the outcomes associated with the available alternatives. The striatum may be important for representing the values of actions. We examined this in monkeys performing an oculomotor choice task. The activity of phasically active neurons (PANs) in the striatum covaried with two classes of information: action-values and chosen-values. Action-value PANs were correlated with value estimates for one of the available actions, and these signals were frequently observed before movement execution. Chosen-value PANs were correlated with the value of the action that had been chosen, and these signals were primarily observed later in the task, immediately before or persistently after movement execution. These populations may serve distinct functions mediated by the striatum: some PANs may participate in choice by encoding the values of the available actions, while other PANs may participate in evaluative updating by encoding the reward value of chosen actions.

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A map for horizontal disparity in monkey V2.

Publication Date: 2008 May 8 PMID: 18466753
Authors: Chen, G. - Lu, H. D. - Roe, A. W.
Journal: Neuron

The perception of visual depth is determined by integration of spatial disparities of inputs from the two eyes. Single cells in visual cortex of monkeys are known to respond to specific binocular disparities; however, little is known about their functional organization. We now show, using intrinsic signal optical imaging and single-unit physiology, that, in the thick stripe compartments of the second visual area (V2), there is a clustered organization of Near cells and Far cells, and moreover, there are topographic maps for Near to Far disparities within V2. Our findings suggest that maps for visual disparity are calculated in V2, and demonstrate parallels in functional organization between the thin, pale, and thick stripes of V2.

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Transient induced gamma-band response in EEG as a manifestation of miniature saccades.

Publication Date: 2008 May 8 PMID: 18466752
Authors: Yuval-Greenberg, S. - Tomer, O. - Keren, A. S. - Nelken, I. - Deouell, L. Y.
Journal: Neuron

The induced gamma-band EEG response (iGBR) recorded on the scalp is widely assumed to reflect synchronous neural oscillation associated with object representation, attention, memory, and consciousness. The most commonly reported EEG iGBR is a broadband transient increase in power at the gamma range approximately 200-300 ms following stimulus onset. A conspicuous feature of this iGBR is the trial-to-trial poststimulus latency variability, which has been insufficiently addressed. Here, we show, using single-trial analysis of concomitant EEG and eye tracking, that this iGBR is tightly time locked to the onset of involuntary miniature eye movements and reflects a saccadic "spike potential." The time course of the iGBR is related to an increase in the rate of saccades following a period of poststimulus saccadic inhibition. Thus, whereas neuronal gamma-band oscillations were shown conclusively with other methods, the broadband transient iGBR recorded by scalp EEG reflects properties of miniature saccade dynamics rather than neuronal oscillations.

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Assessing the function of motor cortex: single-neuron models of how neural response is modulated by limb biomechanics.

Publication Date: 2008 May 8 PMID: 18466751
Authors: Ajemian, R. - Green, A. - Bullock, D. - Sergio, L. - Kalaska, J. - Grossberg, S.
Journal: Neuron

Do neurons in primary motor cortex encode the generative details of motor behavior, such as individual muscle activities, or do they encode high-level movement attributes? Resolving this question has proven difficult, in large part because of the sizeable uncertainty inherent in estimating or measuring the joint torques and muscle forces that underlie movements made by biological limbs. We circumvented this difficulty by considering single-neuron responses in an isometric task, where joint torques and muscle forces can be straightforwardly computed from limb geometry. The response for each neuron was modeled as a linear function of a "preferred" joint torque vector, and this model was fit to individual neural responses across variations in limb posture. The resulting goodness of fit suggests that neurons in motor cortex do encode the kinetics of motor behavior and that the neural response properties of "preferred direction" and "gain" are dual components of a unitary response vector.

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Homeostatic matching and nonlinear amplification at identified central synapses.

Publication Date: 2008 May 8 PMID: 18466750
Authors: Kazama, H. - Wilson, R. I.
Journal: Neuron

Here we describe the properties of a synapse in the Drosophila antennal lobe and show how they can explain certain sensory computations in this brain region. The synapse between olfactory receptor neurons (ORNs) and projection neurons (PNs) is very strong, reflecting a large number of release sites and high release probability. This is likely one reason why weak ORN odor responses are amplified in PNs. Furthermore, the amplitude of unitary synaptic currents in a PN is matched to the size of its dendritic arbor. This matching may compensate for a lower input resistance of larger dendrites to produce uniform depolarization across PN types. Consistent with this idea, a genetic manipulation that lowers input resistance increases unitary synaptic currents. Finally, strong stimuli produce short-term depression at this synapse. This helps explain why PN odor responses are transient, and why strong ORN odor responses are not amplified as powerfully as weak responses.

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K+ channels at the axon initial segment dampen near-threshold excitability of neocortical fast-spiking GABAergic interneurons.

Publication Date: 2008 May 8 PMID: 18466749
Authors: Goldberg, E. M. - Clark, B. D. - Zagha, E. - Nahmani, M. - Erisir, A. - Rudy, B.
Journal: Neuron

Fast-spiking cells (FS cells) are a prominent subtype of neocortical GABAergic interneurons with important functional roles. Multiple FS cell properties are coordinated for rapid response. Here, we describe an FS cell feature that serves to gate the powerful inhibition produced by FS cell activity. We show that FS cells in layer 2/3 barrel cortex possess a dampening mechanism mediated by Kv1.1-containing potassium channels localized to the axon initial segment. These channels powerfully regulate action potential threshold and allow FS cells to respond preferentially to large inputs that are fast enough to "outrun" Kv1 activation. In addition, Kv1.1 channel blockade converts the delay-type discharge pattern of FS cells to one of continuous fast spiking without influencing the high-frequency firing that defines FS cells. Thus, Kv1 channels provide a key counterbalance to the established rapid-response characteristics of FS cells, regulating excitability through a unique combination of electrophysiological properties and discrete subcellular localization.

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Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation.

Publication Date: 2008 May 8 PMID: 18466748
Authors: Song, Y. - Cygnar, K. D. - Sagdullaev, B. - Valley, M. - Hirsh, S. - Stephan, A. - Reisert, J. - Zhao, H.
Journal: Neuron

Ca(2+)/calmodulin-mediated negative feedback is a prototypical regulatory mechanism for Ca(2+)-permeable ion channels. In olfactory sensory neurons (OSNs), such regulation on the cyclic nucleotide-gated (CNG) channel is considered a major mechanism of OSN adaptation. To determine the role of Ca(2+)/calmodulin desensitization of the olfactory CNG channel, we introduced a mutation in the channel subunit CNGB1b in mice that rendered the channel resistant to fast desensitization by Ca(2+)/calmodulin. Contrary to expectations, mutant OSNs showed normal receptor current adaptation to repeated stimulation. Rather, they displayed slower response termination and, consequently, reduced ability to transmit olfactory information to the olfactory bulb. They also displayed reduced response decline during sustained odorant exposure. These results suggest that Ca(2+)/calmodulin-mediated CNG channel fast desensitization is less important in regulating the sensitivity to recurring stimulation than previously thought and instead functions primarily to terminate OSN responses.

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A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating.

Publication Date: 2008 May 8 PMID: 18466747
Authors: Myers, B. R. - Bohlen, C. J. - Julius, D.
Journal: Neuron

TRP cation channels function as cellular sensors in uni- and multicellular eukaryotes. Despite intensive study, the mechanisms of TRP channel activation by chemical or physical stimuli remain poorly understood. To identify amino acid residues crucial for TRP channel gating, we developed an unbiased, high-throughput genetic screen in yeast that uncovered rare, constitutively active mutants of the capsaicin receptor, TRPV1. We show that mutations within the pore helix domain dramatically increase basal channel activity and responsiveness to chemical and thermal stimuli. Mutation of corresponding residues within two related TRPV channels leads to comparable effects on their activation properties. Our data suggest that conformational changes in the outer pore region are critical for determining the balance between open and closed states, providing evidence for a general role for this domain in TRP channel activation.

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An RNAi screen identifies genes that regulate GABA synapses.

Publication Date: 2008 May 8 PMID: 18466746
Authors: Vashlishan, A. B. - Madison, J. M. - Dybbs, M. - Bai, J. - Sieburth, D. - Ch'ng, Q. - Tavazoie, M. - Kaplan, J. M.
Journal: Neuron

GABA synapses play a critical role in many aspects of circuit development and function. For example, conditions that perturb GABA transmission have been implicated in epilepsy. To identify genes that regulate GABA transmission, we performed an RNAi screen for genes whose inactivation increases the activity of C. elegans body muscles, which receive direct input from GABAergic motor neurons. We identified 90 genes, 21 of which were previously implicated in seizure syndromes, suggesting that this screen has effectively identified candidate genes for epilepsy. Electrophysiological recordings and imaging of excitatory and inhibitory synapses indicate that several genes alter muscle activity by selectively regulating GABA transmission. In particular, we identify two humoral pathways and several protein kinases that modulate GABA transmission but have little effect on excitatory transmission at cholinergic neuromuscular junctions. Our data suggest these conserved genes are components of signaling pathways that regulate GABA transmission and consequently may play a role in epilepsy and other cognitive or psychiatric disorders.

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Cannabinoid receptor blockade reveals parallel plasticity mechanisms in different layers of mouse visual cortex.

Publication Date: 2008 May 8 PMID: 18466745
Authors: Liu, C. H. - Heynen, A. J. - Shuler, M. G. - Bear, M. F.
Journal: Neuron

The ocular dominance (OD) shift that occurs in visual cortex after brief monocular deprivation (MD) is a classic model of experience-dependent cortical plasticity. It has been suggested that OD plasticity in layer 2/3 of visual cortex precedes and is necessary for plasticity in the thalamocortical input layer 4. Here, we show in mouse visual cortex that rapid OD plasticity occurs simultaneously in layers 2/3 and 4. Remarkably, pharmacological blockade of cannabinoid receptors completely prevents the OD shift in layer 2/3, leaving plasticity intact in layer 4. Thus, experience-dependent cortical modifications in layers 2/3 and 4 can occur in parallel, via distinct mechanisms. These findings simplify the mechanistic description of plasticity in layer 4, force a revision in the interpretation of previous studies in which laminar differences in OD plasticity mechanisms were unrecognized, and have important implications for the therapeutic use of cannabinoid receptor antagonists in humans.

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Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification.

Publication Date: 2008 May 8 PMID: 18466744
Authors: Dallos, P. - Wu, X. - Cheatham, M. A. - Gao, J. - Zheng, J. - Anderson, C. T. - Jia, S. - Wang, X. - Cheng, W. H. - Sengupta, S. - He, D. Z. - Zuo, J.
Journal: Neuron

It is a central tenet of cochlear neurobiology that mammalian ears rely on a local, mechanical amplification process for their high sensitivity and sharp frequency selectivity. While it is generally agreed that outer hair cells provide the amplification, two mechanisms have been proposed: stereociliary motility and somatic motility. The latter is driven by the motor protein prestin. Electrophysiological phenotyping of a prestin knockout mouse intimated that somatic motility is the amplifier. However, outer hair cells of knockout mice have significantly altered mechanical properties, making this mouse model unsatisfactory. Here, we study a mouse model without alteration to outer hair cell and organ of Corti mechanics or to mechanoelectric transduction, but with diminished prestin function. These animals have knockout-like behavior, demonstrating that prestin-based electromotility is required for cochlear amplification.

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Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsion.

Publication Date: 2008 May 8 PMID: 18466743
Authors: Chen, Z. - Gore, B. B. - Long, H. - Ma, L. - Tessier-Lavigne, M.
Journal: Neuron

Alternative splicing provides a means to increase the complexity of gene function in numerous biological processes, including nervous system wiring. Navigating axons switch responses from attraction to repulsion at intermediate targets, allowing them to grow to each intermediate target and then to move on. The mechanisms underlying this switch remain poorly characterized. We previously showed that the Slit receptor Robo3 is required for spinal commissural axons to enter and cross the midline intermediate target. We report here the existence of two functionally antagonistic isoforms of Robo3 with distinct carboxy termini arising from alternative splicing. Robo3.1 is deployed on the precrossing and crossing portions of commissural axons and allows midline crossing by silencing Slit repulsion. Robo3.2 becomes expressed on the postcrossing portion and blocks midline recrossing, favoring Slit repulsion. The tight spatial regulation of opponent splice variants helps ensure high-fidelity transition of axonal responses from attraction to repulsion at the midline.

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The reorienting system of the human brain: from environment to theory of mind.

Publication Date: 2008 May 8 PMID: 18466742
Authors: Corbetta, M. - Patel, G. - Shulman, G. L.
Journal: Neuron

Survival can depend on the ability to change a current course of action to respond to potentially advantageous or threatening stimuli. This "reorienting" response involves the coordinated action of a right hemisphere dominant ventral frontoparietal network that interrupts and resets ongoing activity and a dorsal frontoparietal network specialized for selecting and linking stimuli and responses. At rest, each network is distinct and internally correlated, but when attention is focused, the ventral network is suppressed to prevent reorienting to distracting events. These different patterns of recruitment may reflect inputs to the ventral attention network from the locus coeruleus/norepinephrine system. While originally conceptualized as a system for redirecting attention from one object to another, recent evidence suggests a more general role in switching between networks, which may explain recent evidence of its involvement in functions such as social cognition.

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Finding gamma.

Publication Date: 2008 May 8 PMID: 18466741
Authors: Fries, P. - Scheeringa, R. - Oostenveld, R.
Journal: Neuron

Neuronal gamma-band synchronization is central for cognition. Respective studies in human subjects focused on a visually induced transient enhancement of broadband EEG power. In this issue of Neuron, Yuval-Greenberg et al. demonstrate that this EEG response is an artifact of microsaccades, raising the question of whether gamma-band synchronization can be assessed with EEG.

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What to do, or how to do it?

Publication Date: 2008 May 8 PMID: 18466740
Authors: Pesaran, B. - Movshon, J. A.
Journal: Neuron

In this issue of Neuron, Ajemian et al. present a computational model of the activity of neurons in primary motor cortex (M1) during isometric movements in different postures. By modeling the output of M1 neurons in terms of their influence on muscles, they find each M1 neuron maps its output into a particular pattern of muscle actions.

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Silencing the cochlear amplifier by immobilizing prestin.

Publication Date: 2008 May 8 PMID: 18466739
Authors: Muller, U. - Gillespie, P.
Journal: Neuron

Achieving the exquisite sensitivity and frequency selectivity of the mammalian ear requires active amplification of input sound. In this issue of Neuron, Dallos and colleagues demonstrate that the molecular motor prestin, which drives shape changes in the soma of mechanosensory hair cells, underlies mechanical feedback mechanisms for sound amplification in mammals.

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To cross or not to cross: alternatively spliced forms of the Robo3 receptor regulate discrete steps in axonal midline crossing.

Publication Date: 2008 May 8 PMID: 18466738
Authors: Black, D. L. - Zipursky, S. L.
Journal: Neuron

How growth cones grow toward and then away from intermediate targets is a key issue in axon guidance. In this issue of Neuron, Tessier-Lavigne and colleagues demonstrate that two different spliced isoforms of the Robo3 receptor act sequentially in commissural neuron growth cones to mediate this process at the ventral midline in the vertebrate spinal cord.

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Processing of social and monetary rewards in the human striatum.

Publication Date: 2008 Apr 24 PMID: 18439412
Authors: Izuma, K. - Saito, D. N. - Sadato, N.
Journal: Neuron

Despite an increasing focus on the neural basis of human decision making in neuroscience, relatively little attention has been paid to decision making in social settings. Moreover, although human social decision making has been explored in a social psychology context, few neural explanations for the observed findings have been considered. To bridge this gap and improve models of human social decision making, we investigated whether acquiring a good reputation, which is an important incentive in human social behaviors, activates the same reward circuitry as monetary rewards. In total, 19 subjects participated in functional magnetic resonance imaging (fMRI) experiments involving monetary and social rewards. The acquisition of one's good reputation robustly activated reward-related brain areas, notably the striatum, and these overlapped with the areas activated by monetary rewards. Our findings support the idea of a "common neural currency" for rewards and represent an important first step toward a neural explanation for complex human social behaviors.

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Know your place: neural processing of social hierarchy in humans.

Publication Date: 2008 Apr 24 PMID: 18439411
Authors: Zink, C. F. - Tong, Y. - Chen, Q. - Bassett, D. S. - Stein, J. L. - Meyer-Lindenberg, A.
Journal: Neuron

Social hierarchies guide behavior in many species, including humans, where status also has an enormous impact on motivation and health. However, little is known about the underlying neural representation of social hierarchies in humans. In the present study, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive, simulated social context. In both stable and unstable social hierarchies, viewing a superior individual differentially engaged perceptual-attentional, saliency, and cognitive systems, notably dorsolateral prefrontal cortex. In the unstable hierarchy setting, additional regions related to emotional processing (amygdala), social cognition (medial prefrontal cortex), and behavioral readiness were recruited. Furthermore, social hierarchical consequences of performance were neurally dissociable and of comparable salience to monetary reward, providing a neural basis for the high motivational value of status. Our results identify neural mechanisms that may mediate the enormous influence of social status on human behavior and health.

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Both the hippocampus and striatum are involved in consolidation of motor sequence memory.

Publication Date: 2008 Apr 24 PMID: 18439410
Authors: Albouy, G. - Sterpenich, V. - Balteau, E. - Vandewalle, G. - Desseilles, M. - Dang-Vu, T. - Darsaud, A. - Ruby, P. - Luppi, P. H. - Degueldre, C. - Peigneux, P. - Luxen, A. - Maquet, P.
Journal: Neuron

Functional magnetic resonance imaging (fMRI) was used to investigate the cerebral correlates of motor sequence memory consolidation. Participants were scanned while training on an implicit oculomotor sequence learning task and during a single testing session taking place 30 min, 5 hr, or 24 hr later. During training, responses observed in hippocampus and striatum were linearly related to the gain in performance observed overnight, but not over the day. Responses in both structures were significantly larger at 24 hr than at 30 min or 5 hr. Additionally, the competitive interaction observed between these structures during training became cooperative overnight. These results stress the importance of both hippocampus and striatum in procedural memory consolidation. Responses in these areas during training seem to condition the overnight memory processing that is associated with a change in their functional interactions. These results show that both structures interact during motor sequence consolidation to optimize subsequent behavior.

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Cortical mechanisms of smooth eye movements revealed by dynamic covariations of neural and behavioral responses.

Publication Date: 2008 Apr 24 PMID: 18439409
Authors: Schoppik, D. - Nagel, K. I. - Lisberger, S. G.
Journal: Neuron

Neural activity in the frontal eye fields controls smooth pursuit eye movements, but the relationship between single neuron responses, cortical population responses, and eye movements is not well understood. We describe an approach to dynamically link trial-to-trial fluctuations in neural responses to parallel variations in pursuit and demonstrate that individual neurons predict eye velocity fluctuations at particular moments during the course of behavior, while the population of neurons collectively tiles the entire duration of the movement. The analysis also reveals the strength of correlations in the eye movement predictions derived from pairs of simultaneously recorded neurons and suggests a simple model of cortical processing. These findings constrain the primate cortical code for movement, suggesting that either a few neurons are sufficient to drive pursuit at any given time or that many neurons operate collectively at each moment with remarkably little variation added to motor command signals downstream from the cortex.

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Multiple actions of spinophilin regulate mu opioid receptor function.

Publication Date: 2008 Apr 24 PMID: 18439408
Authors: Charlton, J. J. - Allen, P. B. - Psifogeorgou, K. - Chakravarty, S. - Gomes, I. - Neve, R. L. - Devi, L. A. - Greengard, P. - Nestler, E. J. - Zachariou, V.
Journal: Neuron

Spinophilin, a dendritic spine-enriched scaffold protein, modulates synaptic transmission via multiple functions mediated by distinct domains of the protein. Here, we show that spinophilin is a key modulator of opiate action. Knockout of the spinophilin gene causes reduced sensitivity to the analgesic effects of morphine and early development of tolerance but a higher degree of physical dependence and increased sensitivity to the rewarding actions of the drug. At the cellular level, spinophilin associates with the mu opioid receptor (MOR) in striatum and modulates MOR signaling and endocytosis. Activation of MOR by opiate agonists such as fentanyl and morphine promotes these events, which feedback to suppress MOR responsiveness. Our findings support a potent physiological role of spinophilin in regulating MOR function and provide a potential new target for the treatment of opiate addiction.

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Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging.

Publication Date: 2008 Apr 24 PMID: 18439407
Authors: Shafer, O. T. - Kim, D. J. - Dunbar-Yaffe, R. - Nikolaev, V. O. - Lohse, M. J. - Taghert, P. H.
Journal: Neuron

The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of approximately 150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of approximately 150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network.

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Drosophila ankyrin 2 is required for synaptic stability.

Publication Date: 2008 Apr 24 PMID: 18439406
Authors: Koch, I. - Schwarz, H. - Beuchle, D. - Goellner, B. - Langegger, M. - Aberle, H.
Journal: Neuron

Synaptic connections are stabilized through transsynaptic adhesion complexes that are anchored in the underlying cytoskeleton. The Drosophila neuromuscular junction (NMJs) serves as a model system to unravel genes required for the structural remodeling of synapses. In a mutagenesis screen for regulators of synaptic stability, we recovered mutations in Drosophila ankyrin 2 (ank2) affecting two giant Ank2 isoforms that are specifically expressed in the nervous system and associate with the presynaptic membrane cytoskeleton. ank2 mutant larvae show severe deficits in the stability of NMJs, resulting in a reduction in overall terminal size, withdrawal of synaptic boutons, and disassembly of presynaptic active zones. In addition, lack of Ank2 leads to disintegration of the synaptic microtubule cytoskeleton. Microtubules and microtubule-associated proteins fail to extend into distant boutons. Interestingly, Ank2 functions downstream of spectrin in the anchorage of synaptic microtubules, providing the cytoskeletal scaffold that is essential for synaptic stability.

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A presynaptic giant ankyrin stabilizes the NMJ through regulation of presynaptic microtubules and transsynaptic cell adhesion.

Publication Date: 2008 Apr 24 PMID: 18439405
Authors: Pielage, J. - Cheng, L. - Fetter, R. D. - Carlton, P. M. - Sedat, J. W. - Davis, G. W.
Journal: Neuron

In a forward genetic screen for mutations that destabilize the neuromuscular junction, we identified a novel long isoform of Drosophila ankyrin2 (ank2-L). We demonstrate that loss of presynaptic Ank2-L not only causes synapse disassembly and retraction but also disrupts neuronal excitability and NMJ morphology. We provide genetic evidence that ank2-L is necessary to generate the membrane constrictions that normally separate individual synaptic boutons and is necessary to achieve the normal spacing of subsynaptic protein domains, including the normal organization of synaptic cell adhesion molecules. Mechanistically, synapse organization is correlated with a lattice-like organization of Ank2-L, visualized using extended high-resolution structured-illumination microscopy. The stabilizing functions of Ank2-L can be mapped to the extended C-terminal domain that we demonstrate can directly bind and organize synaptic microtubules. We propose that a presynaptic Ank2-L lattice links synaptic membrane proteins and spectrin to the underlying microtubule cytoskeleton to organize and stabilize the presynaptic terminal.

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Expression of long-term depression underlies visual recognition memory.

Publication Date: 2008 Apr 24 PMID: 18439404
Authors: Griffiths, S. - Scott, H. - Glover, C. - Bienemann, A. - Ghorbel, M. T. - Uney, J. - Brown, M. W. - Warburton, E. C. - Bashir, Z. I.
Journal: Neuron

The modifications occurring in the brain during learning and memory are still poorly understood but may involve long-lasting changes in synaptic transmission (synaptic plasticity). In perirhinal cortex, a lasting decrement in neuronal responsiveness is associated with visual familiarity discrimination, leading to the hypothesis that long-term depression (LTD)-like synaptic plasticity may underlie recognition memory. LTD relies on internalization of AMPA receptors (AMPARs) through interaction between their GluR2 subunits and AP2, the clathrin adaptor protein required for endocytosis. We demonstrate that a peptide that blocks interactions between GluR2 and AP2 blocks LTD in perirhinal cortex in vitro. Viral transduction of this peptide in perirhinal cortex produced striking deficits in visual recognition memory. Furthermore, there was a deficit of LTD in perirhinal cortex slices from virally transduced, recognition memory-deficient animals. These results suggest that internalization of AMPA receptors, a process critical for the expression of LTD in perirhinal cortex, underlies visual recognition memory.

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TRPV1 gene required for thermosensory transduction and anticipatory secretion from vasopressin neurons during hyperthermia.

Publication Date: 2008 Apr 24 PMID: 18439403
Authors: Sharif-Naeini, R. - Ciura, S. - Bourque, C. W.
Journal: Neuron

Increases in core body temperature promote thermoregulatory cooling by stimulating sweat production and preemptive renal water reabsorption through the release of vasopressin (VP, antidiuretic hormone). The mechanism by which the hypothalamus orchestrates this anticipatory VP release during hyperthermia is unknown but has been linked to a central thermosensory mechanism. Here, we report that thermal stimuli spanning core body temperatures activate a calcium-permeable, ruthenium red- and SB366791-sensitive nonselective cation conductance in hypothalamic VP neurons. This response is associated with a depolarizing receptor potential and an increase in action potential firing rate, indicating that these neurons are intrinsically thermosensitive. The thermosensitivity of VP neurons isolated from trpv1 knockout (Trpv1(-/-)) mice was significantly lower than that of wild-type counterparts. Moreover, Trpv1(-/-) mice showed an impaired VP response to hyperthermia in vivo. Channels encoded by the trpv1 gene thus confer thermosensitivity in central VP neurons and contribute to the thermal control of VP release in vivo.

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Astrocytes in the epileptic brain.

Publication Date: 2008 Apr 24 PMID: 18439402
Authors: Wetherington, J. - Serrano, G. - Dingledine, R.
Journal: Neuron

The roles that astrocytes play in the evolution of abnormal network excitability in chronic neurological disorders involving brain injury, such as acquired epilepsy, are receiving renewed attention due to improved understanding of the molecular events underpinning the physiological functions of astrocytes. In epileptic tissue, evidence is pointing to enhanced chemical signaling and disrupted linkage between water and potassium balance by reactive astrocytes, which together conspire to enhance local synchrony in hippocampal microcircuits. Reactive astrocytes in epileptic tissue both promote and oppose seizure development through a variety of specific mechanisms; the new findings suggest several novel astrocyte-related targets for drug development.

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Schizophrenia: genome, interrupted.

Publication Date: 2008 Apr 24 PMID: 18439401
Authors: Cantor, R. M. - Geschwind, D. H.
Journal: Neuron

Structural chromosomal variation is increasingly recognized as an important contributor to human diseases, particularly those of neurodevelopment, such as autism. A current paper makes a significant advance to schizophrenia genetics by establishing an association with rare copy number variants (CNV), which are over-represented in neurodevelopmental genes.

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For love or money: a common neural currency for social and monetary reward.

Publication Date: 2008 Apr 24 PMID: 18439400
Authors: Saxe, R. - Haushofer, J.
Journal: Neuron

Two papers in the current issue of Neuron (Izuma et al. and Zink et al.) report that activity in specific regions of the brain, especially the striatum, reflects a common signal of reward in both the economic (e.g., money) and social (e.g., praise and status) domains.

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Cyclic AMP imaging sheds light on PDF signaling in circadian clock neurons.

Publication Date: 2008 Apr 24 PMID: 18439399
Authors: Tomchik, S. M. - Davis, R. L.
Journal: Neuron

In Drosophila, the neuropeptide PDF is required for circadian rhythmicity, but it is unclear where PDF acts. In this issue of Neuron, Shafer et al. use a novel bioimaging methodology to demonstrate that PDF elevates cAMP in nearly all clock neurons. Thus, PDF apparently exerts more widespread effects on the circadian clock network than suggested by previous studies of PDF receptor expression.

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The barista on the bus: cellular and synaptic mechanisms for visual recognition memory.

Publication Date: 2008 Apr 24 PMID: 18439398
Authors: Barth, A. L. - Wheeler, M. E.
Journal: Neuron

Our ability to recognize that something is familiar, often referred to as visual recognition memory, has been correlated with a reduction in neural activity in the perirhinal cortex. In this issue of Neuron, Griffiths et al. now provide evidence that this form of memory requires AMPA receptor endocytosis and long-term depression of excitatory synapses in this brain area.

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