Current Opinion in Neurobiology

Machines that learn to segment images: a crucial technology for connectomics.

Publication Date: 2010 Aug 27 PMID: 20801638
Authors: Jain, V. - Seung, H. S. - Turaga, S. C.
Journal: Curr Opin Neurobiol

Connections between neurons can be found by checking whether synapses exist at points of contact, which in turn are determined by neural shapes. Finding these shapes is a special case of image segmentation, which is laborious for humans and would ideally be performed by computers. New metrics properly quantify the performance of a computer algorithm using its disagreement with 'true' segmentations of example images. New machine learning methods search for segmentation algorithms that minimize such metrics. These advances have reduced computer errors dramatically. It should now be faster for a human to correct the remaining errors than to segment an image manually. Further reductions in human effort are expected, and crucial for finding connectomes more complex than that of Caenorhabditis elegans.

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A step-by-step guide to visual circuit assembly in Drosophila.

Publication Date: 2010 Aug 25 PMID: 20800474
Authors: Hadjieconomou, D. - Timofeev, K. - Salecker, I.
Journal: Curr Opin Neurobiol

The ability of vertebrates and insects to perceive and process information about the visual world is mediated by neural circuits, which share a strikingly conserved architecture of reiterated columnar and layered synaptic units. Recent genetic approaches conferring single-cell resolution have enabled major advances in our understanding of the cellular and molecular strategies that orchestrate visual circuit assembly in Drosophila. Photoreceptor axon targeting relies on a sequence of interdependent developmental steps to achieve temporal coordination with the formation and maturation of partner neurons. Distinct targeting events depend on anterograde and autocrine signaling, neuron-glia interactions, axon tiling and the timely expression of homophilic cell surface molecules. These mediate local adhesive or repulsive interactions of photoreceptor axons with each other and with target neurons.

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The single dendritic branch as a fundamental functional unit in the nervous system.

Publication Date: 2010 Aug 25 PMID: 20800473
Authors: Branco, T. - Hausser, M.
Journal: Curr Opin Neurobiol

The conventional view of dendritic function is that dendrites collect synaptic input and deliver it to the soma. This view has been challenged in recent years by new results demonstrating that dendrites can act as independent processing and signalling units, performing local computations that are then broadcast to the rest of the neuron, or to other neurons via dendritic transmitter and neuromodulator release. Here we describe these findings and discuss the notion that the single dendritic branch may represent a fundamental unit of signalling in the mammalian nervous system. This view proposes that the dendritic branch is a basic organizational unit for integrating synaptic input, implementing synaptic and homeostatic plasticity, and controlling local cellular processes such as protein translation.

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Micro-scale and microfluidic devices for neurobiology.

Publication Date: 2010 Aug 23 PMID: 20739175
Authors: Taylor, A. M. - Jeon, N. L.
Journal: Curr Opin Neurobiol

The precise spatial and temporal control afforded by microfluidic devices make them uniquely suited as experimental tools for cellular neuroscience. Micro-structures have been developed to direct the placement of cells and small organisms within a device. Microfluidics can precisely define pharmacological microenvironments, mimicking conditions found in vivo with the advantage of defined parameters which are usually difficult to control and manipulate in vivo. These devices are compatible with high-resolution microscopy, are simple to assemble, and are reproducible. In this review we will focus on microfluidic devices that have recently been developed for small, whole organisms such as C. elegans and dissociated cultured neurons. These devices have improved control over the placement of cells or organisms and allowed unprecedented experimental access, enabling novel investigations in neurobiology.

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Signaling mechanisms.

Publication Date: 2010 Aug 21 PMID: 20732806
Authors: Van Aelst, L. - Caroni, P.
Journal: Curr Opin Neurobiol

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Spine plasticity in the motor cortex.

Publication Date: 2010 Aug 19 PMID: 20728341
Authors: Yu, X. - Zuo, Y.
Journal: Curr Opin Neurobiol

Dendritic spines are the postsynaptic sites of the majority of excitatory synapses in the mammalian central nervous system. The morphology and dynamics of dendritic spines change throughout the lifespan of animals, in response to novel experiences and neuropathologies. New spines form rapidly as animals learn new tasks or experience novel sensory stimulations. This is followed by a selective elimination of previously existing spines, leading to significant synaptic remodeling. In the brain damaged by injuries or neurological diseases, spines in surviving cortical regions turn over substantially, potentially forming new synaptic connections to adopt the function lost in the damaged region. These findings suggest that spine plasticity plays important roles in the formation and maintenance of a functional neural circuitry.

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New resolving power for light microscopy: applications to neurobiology.

Publication Date: 2010 Aug 19 PMID: 20728340
Authors: Dani, A. - Huang, B.
Journal: Curr Opin Neurobiol

The recent invention of super-resolution fluorescence microscopy brings more than an order of magnitude gain in the spatial resolution of light microscopy. New opportunities keep emerging with the multicolor, three-dimensional, and live imaging functionalities gained in the past three years. The power of this technology has been demonstrated by imaging the organization of organelles and molecular complexes, with recent applications increasingly showing its potential in neurobiology. These developments are exemplified by the visualization of components inside dendritic spines to fine morphologies of neurons. In combination with correlative electron microscopy, functional imaging, and electrical/optogenetic stimulation tools, super-resolution fluorescence microscopy has the potential to provide further insights ranging from the molecular details of neurons up to the functional mechanisms of neuronal circuits.

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Further tales of the midline.

Publication Date: 2010 Aug 17 PMID: 20724139
Authors: Chedotal, A.
Journal: Curr Opin Neurobiol

In the vertebrate central nervous system (CNS), specialized glial and neuronal cells positioned at the dorsal and ventral midline act as intermediate targets for commissural axons by secreting a variety of attractants and repellents. Despite the diversity of commissural projections, recent findings suggest that the same basic set of molecules controls midline crossing at all level of the CNS. Midline crossing is associated with an important switch of the combinatorial expression of several axon guidance receptors on the growth cone of commissural axons. I will review here novel studies that reveal how the expression of these receptors and the activity of their ligands are modulated by transcriptional, translational, and post-translational modifications. This also uncovers extensive cross talks between axon guidance pathways.

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Functional polarity in neurons: what can we learn from studying an exception?

Publication Date: 2010 Aug 17 PMID: 20724138
Authors: Urban, N. N. - Castro, J. B.
Journal: Curr Opin Neurobiol

Dendrites and axons typically handle very different aspects of neuronal signaling. However, many of the functional distinctions between these two types of processes are absent in neurons with release-competent dendrites. This raises fundamental questions about the molecular mechanisms that promote and permit functional specialization, and suggests that the 'exceptional' case of presynaptic dendrites may provide important clues on how neuronal polarity is established. To help stimulate thinking on this new front, we summarize some key aspects of the physiology of dendritic neurotransmitter release, together with recent work on the molecular basis of neuronal polarity.

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Microglia dynamics and function in the CNS.

Publication Date: 2010 Aug 10 PMID: 20705452
Authors: Parkhurst, C. N. - Gan, W. B.
Journal: Curr Opin Neurobiol

Microglial cells constitute the resident immune cell population of the mammalian central nervous system. One striking feature of these cells is their highly dynamic nature under both normal and pathological brain conditions. The highly branched processes of resting microglia display a constitutive mobility and undergo rapid directional movement towards sites of acute tissue disruption. Microglia can be converted by a large number of different stimuli to a chronically activated state by signaling through both purinergic and Toll-like receptor systems, among others. Recent work has uncovered some of the mechanisms underlying microglia dynamics and shed new light into the functional significance of this enigmatic member of the glial cell family.

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Plasticity of voltage-gated ion channels in pyramidal cell dendrites.

Publication Date: 2010 Aug 4 PMID: 20691582
Authors: Remy, S. - Beck, H. - Yaari, Y.
Journal: Curr Opin Neurobiol

Dendrites of pyramidal neurons integrate multiple synaptic inputs and transform them into axonal action potential output. This fundamental process is controlled by a variety of dendritic channels. The properties of dendritic ion channels are not static but can be modified by neuronal activity. Activity-dependent changes in the density, localization, or biophysical properties of dendritic voltage-gated channels can persistently alter the integration of synaptic inputs. Furthermore, dendritic intrinsic plasticity can induce neuronal output mode transitions (e.g. from regular spiking to burst firing). Recent advances in the field reviewed here represent an important step toward uncovering the principles of neuronal input/output transformations in response to various patterns of brain activity.

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Microbial rhodopsins in the spotlight.

Publication Date: 2010 Aug 4 PMID: 20691581
Authors: Bamann, C. - Nagel, G. - Bamberg, E.
Journal: Curr Opin Neurobiol

The discovery of the light-gated cation channel Channelrhodopsin-2 (ChR2) and the use of the rediscovered light-driven Cl-pump halorhodopsin (HR) as optogenetic tools-genetically encoded switches that enable neurons to be turned on or off with bursts of light-refines the functional study of neurons in larger networks. Cell-specific expression allows a fast optical scanning approach to determine neuronal crosstalk following plasticity at the single synapse level or long-range projections in locomotion and somatosensory networks. Both rhodopsins proved to work functionally and could evoke behavioral responses in lower model organisms, reinstall rudimentary visual perception in blind mice and were set in a biomedical context with the investigation of neurodegenerative diseases.

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Chemical reporters for the illumination of protein and cell dynamics.

Publication Date: 2010 Aug 5 PMID: 20650631
Authors: Dieterich, D. C.
Journal: Curr Opin Neurobiol

Fluorescent proteins have revolutionized cell biology and, therefore, our understanding of the complex molecular and cellular mechanisms that wire the brain together and enable its plasticity throughout life. The ability to visualize cell biological processes has inspired the development of alternative protein labeling strategies by both chemists and biologists. Among those approaches are the introduction of small bioorthogonal chemical reporters and new fluorescent probes by either genetic encoding or by utilizing the cell's own biosynthesis machinery in live cells. This review will highlight recent advances in approaches to track discrete proteins or whole subpopulations of a proteome including post-translational modifications with spatiotemporal resolution.

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