Journal Sciences News
Revue Francophone des Laboratoires
December 2018
Transcription factor mechanisms guiding motor neuron differentiation and diversification
Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53 Author(s): Clinton Cave, Shanthini Sockanathan The embryonic generation of motor neurons is a complex process involving progenitor patterning, fate specification, differentiation, and maturation. Throughout this progression, the differential expression of transcription factors has served as our road map for the eventual cell fate of nascent motor neurons. Recent findings from in vivo and in vitro models of motor neuron development have expanded our understanding of how transcription factors govern motor neuron identity and their individual regulatory mechanisms. With the advent of next generation sequencing approaches, researchers now have unprecedented access to the gene regulatory dynamics involved in motor neuron development and are uncovering new connections linking neurodevelopment and neurodegenerative disease.
December 2018
Molecular diversity underlying cortical excitatory and inhibitory synapse development
Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53 Author(s): Emilia Favuzzi, Beatriz Rico The complexity and precision of cortical circuitries is achieved during development due to the exquisite diversity of synapse types that is generated in a highly regulated manner. Here, we review the recent increase in our understanding of how synapse type-specific molecules differentially regulate the development of excitatory and inhibitory synapses. Moreover, several synapse subtype-specific molecules have been shown to control the targeting, formation or maturation of particular subtypes of excitatory synapses. Because inhibitory neurons are extremely diverse, a similar molecular diversity is likely to underlie the development of different inhibitory synapses making it a promising topic for future investigation in the field of the synapse development.
December 2018
Origin and circuitry of spinal locomotor interneurons generating different speeds
Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53 Author(s): Henrik Boije, Klas Kullander The spinal circuitry governing the undulatory movements of swimming vertebrates consist of excitatory and commissural inhibitory interneurons and motor neurons. This locomotor network generates the rhythmic output, coordinate left/right alternation, and permit communication across segments. Through evolution, more complex movement patterns have emerged, made possible by sub-specialization of neural populations within the spinal cord. Walking tetrapods use a similar basic circuitry, but have added layers of complexity for the coordination of intralimbic flexor and extensor muscles as well as interlimbic coordination between the body halves and fore/hindlimbs. Although the basics of these circuits are known there is a gap in our knowledge regarding how different speeds and gaits are coordinated. Analysing subpopulations among described neuronal populations may bring insight into how changes in locomotor output are orchestrated by a hard-wired network.
December 2018
Experience-dependent plasticity in the lateral geniculate nucleus
Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53 Author(s): Tobias Rose, Tobias Bonhoeffer Experience-dependent plasticity in the visual system is traditionally thought to be exclusively cortical whereas the dorsal lateral geniculate nucleus (dLGN) is classically considered to just be a ‘relay’ of visual information between the retina and the cortex. However, a number of recent experiments call into question the simplistic view of visual cortex being the only site of plasticity. Thalamic neurons, at least in mouse dLGN, combine inputs from ganglion cells located in both eyes and recent evidence suggests that the feature selectivity of dLGN neurons is subject to experience-dependent plasticity. Here we discuss new insights into the nature of thalamic visual processing, focusing on the unexpected degree and plasticity of functional binocular convergence in mouse dLGN.
December 2018
Development of the whisker-to-barrel cortex system
Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53 Author(s): Jenq-Wei Yang, Werner Kilb, Sergei Kirischuk, Petr Unichenko, Maik C St
December 2018
Cortical developmental death: selected to survive or fated to die
Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53 Author(s): Fr
October 2018
Constraints on somatosensory map development: mutants lead the way
Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53 Author(s): Patricia Gaspar, Nicolas Renier In the rodent somatosensory system, the disproportionally large whisker representation and their specialization into barrel-shaped units in the different sensory relays has offered experimentalists with an ideal tool to identify mechanisms involved in brain map formation. These combine three intertwined constraints: Firstly, fasciculation of the incoming axons; secondly, early neural activity; finally, molecular patterning. Sophisticated genetic manipulations in mice have now allowed dissecting these mechanisms with greater accuracy. Here we discuss some recent papers that provided novel insights into how these different mapping rules and constraints interact to shape the barrel map.
October 2018
Socio-sexual processing in cortical circuits
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Michael Brecht, Constanze Lenschow, Rajnish P Rao How does social and sexual information processing map onto cortical circuits? Addressing this question has been difficult, because of a lack of circuit-oriented social neuroscience and an absence of measurements from interacting brains. Recent work showed social information is already differentially processed in the primary sensory cortices. Converging evidence suggests that prefrontal areas contribute to social interaction processing and determining social hierarchies. In social interactions, we identify gender in split seconds, but after centuries of anatomy we are still unable to distinguish male and female cortices. Novel data reinforce the idea of a bisexual layout of cortical anatomy. Physiological analysis, however, provided evidence for sex differences in cortical processing. Unlike other cortical circuits, sexual processing circuits undergo major rewiring and expansion during puberty and show lasting damage from childhood abuse.
October 2018
Vestibular signals in primate cortex for self-motion perception
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Yong Gu The vestibular peripheral organs in our inner ears detect transient motion of the head in everyday life. This information is sent to the central nervous system for automatic processes such as vestibulo-ocular reflexes, balance and postural control, and higher cognitive functions including perception of self-motion and spatial orientation. Recent neurophysiological studies have discovered a prominent vestibular network in the primate cerebral cortex. Many of the areas involved are multisensory: their neurons are modulated by both vestibular signals and visual optic flow, potentially facilitating more robust heading estimation through cue integration. Combining psychophysics, computation, physiological recording and causal manipulation techniques, recent work has addressed both the encoding and decoding of vestibular signals for self-motion perception.
October 2018
Behavioral readout of spatio-temporal codes in olfaction
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Edmund Chong, Dmitry Rinberg Neural recordings performed at an increasing scale and resolution have revealed complex, spatio-temporally precise patterns of activity in the olfactory system. Multiple models may explain the functional consequences of the spatio-temporal olfactory code, but the link to behavior remains unclear. Recent evidence in the field suggests a behavioral sensitivity to both fine spatial and temporal features in the code. How these features and combinations of features give rise to olfactory behavior is the subject of active research in the field. Modern genetic and optogenetic methods show great promise in testing the link between olfactory codes and behavior.
October 2018
Neural and genetic basis of dexterous hand movements
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Yutaka Yoshida, Tadashi Isa An ability to control dexterous hand movements is considered to parallel the evolutionary development of the corticospinal tract and the appearance of direct connections between corticospinal neurons and motoneurons (the corticomotoneuronal (CM) pathway), which developed uniquely in higher primates. However, recent studies have revealed that some non-primate animal species have higher levels of dexterity than previously supposed, and in higher primates, various indirect non-CM descending pathways have been shown to participate in the control of dexterous movements. More recently, the CM pathway was shown to exist in rodents during early development, suggesting that rodents and primates diverged in their reliance on the CM pathway at some point in evolution, thus challenging the traditional view of the sequential development of hand control from rodents to primates.
October 2018
Developmental interactions between thalamus and cortex: a true love reciprocal story
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Noelia Ant
October 2018
Personalized brain network models for assessing structure–function relationships
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Kanika Bansal, Johan Nakuci, Sarah Feldt Muldoon Many recent efforts in computational modeling of macro-scale brain dynamics have begun to take a data-driven approach by incorporating structural and/or functional information derived from subject data. Here, we discuss recent work using personalized brain network models to study structure–function relationships in human brains. We describe the steps necessary to build such models and show how this computational approach can provide previously unobtainable information through the ability to perform virtual experiments. Finally, we present examples of how personalized brain network models can be used to gain insight into the effects of local stimulation and improve surgical outcomes in epilepsy.

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October 2018
Active mechanosensory feedback during locomotion in the zebrafish spinal cord
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Steven Knafo, Claire Wyart The investigation of mechanosensory feedback to locomotion has been hindered by the challenge of recording neurons in motion. Genetic accessibility and optical transparency of zebrafish larvae provide means to revisit this question. Glutamatergic Rohon-Beard (RB) and GABAergic CSF-contacting neurons (CSF-cNs) are spinal mechanosensory neurons. Recent studies combining bioluminescence, silencing and optogenetic activation show that mechanosensory neurons enhance speed and stabilize posture during locomotion. RB neurons can modulate speed by projecting onto glutamatergic premotor V2a interneurons during fast swimming, while CSF-cNs inhibit V0-v interneurons sustaining slow swimming. Sensory gating, either through inhibition of sensory interneurons (CoPA) or though the direct inhibition of primary motor neurons by CSF-cNs, mediates postural control. Advanced optical methods have shed light on the dynamics of sensorimotor integration during active locomotion unraveling implications for translational research.
October 2018
Memory circuits: CA2
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Rebecca A Piskorowski, Vivien Chevaleyre The hippocampus is a central region in the coding of spatial, temporal and episodic memory. Recent discoveries have revealed surprising and complex roles of the small area CA2 in hippocampal function. Lesion studies have revealed that this region is required for social memory formation. Area CA2 is targeted by extra-hippocampal paraventricular inputs that release vasopressin and can act to enhance social memory performance. In vivo recordings have revealed nonconventional activity by neurons in this region that act to both initiate hippocampal sharp-wave ripple events as well as encode spatial information during immobility. Silencing of CA2 pyramidal neurons has revealed that this area also acts to control hippocampal network excitability during encoding, and this balance of excitation and inhibition is disrupted in disease. This review summarizes recent findings and attempts to integrate these results into pre-existing models.
October 2018
Neuronal coding mechanisms mediating fear behavior
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Robert R Rozeske, Cyril Herry The behavioral repertoire of an organism can be highly diverse, spanning from social to defensive. How an animal efficiently switches between distinct behaviors is a fundamental question whose inquiry will provide insights into the mechanisms that are necessary for an organism's survival. Previous work aimed at identifying the neural systems responsible for defensive behaviors, such as freezing, has demonstrated critical interactions between the prefrontal cortex and amygdala. Indeed, this foundational research has provided an indispensable anatomical framework that investigators are now using to understand the physiological mechanisms of defined neural circuits within the prefrontal cortex that code for the rapid and flexible expression of defensive behaviors. Here we review recent findings demonstrating temporal and rate coding mechanisms of freezing behavior in the prefrontal cortex. We hypothesize that anatomical features, such as target structure and cortical layer, as well as the nature of the information to be coded, may be critical factors determining the coding scheme. Furthermore, detailed behavioral analyses may reveal subtypes of defensive behaviors that represent the principle factor governing coding selection.
October 2018
Neural encoding of sensory and behavioral complexity in the auditory cortex
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Kishore Kuchibhotla, Brice Bathellier Converging evidence now supports the idea that auditory cortex is an important step for the emergence of auditory percepts. Recent studies have extended the list of complex, nonlinear sound features coded by cortical neurons. Moreover, we are beginning to uncover general properties of cortical representations, such as invariance and discreteness, which reflect the structure of auditory perception. Complexity, however, emerges not only through nonlinear shaping of auditory information into perceptual bricks. Behavioral context and task-related information strongly influence cortical encoding of sounds via ascending neuromodulation and descending top-down frontal control. These effects appear to be mediated through local inhibitory networks. Thus, auditory cortex can be seen as a hub linking structured sensory representations with behavioral variables.
October 2018
Thalamocortical function in developing sensory circuits
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Matthew T Colonnese, Marnie A Phillips Thalamocortical activity patterns, both spontaneous and evoked, undergo a dramatic shift in preparation for the onset of rich sensory experience (e.g. birth in humans; eye-opening in rodents). This change is the result of a switch from thalamocortical circuits tuned for transmission of spontaneous bursting in sense organs, to circuits capable of high resolution, active sensory processing. Early ‘pre-sensory’ tuning uses amplification generated by corticothalamic excitatory feedback and early-born subplate neurons to ensure transmission of bursts, at the expense of stimulus discrimination. The switch to sensory circuits is due, at least in part, to the coordinated remodeling of inhibitory circuits in thalamus and cortex. Appreciation of the distinct rules that govern early circuit function can, and should, inform translational studies of genetic and acquired developmental dysfunction.

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October 2018
What a predator can teach us about visual processing: a lesson from the archerfish
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Mor Ben-Tov, Ohad Ben-Shahar, Ronen Segev The archerfish is a predator with highly unusual visually guided behavior. It is most famous for its ability to hunt by shooting water jets at static or dynamic insect prey, up to two meters above the water's surface. In the lab, the archerfish can learn to distinguish and shoot at artificial targets presented on a computer screen, thus enabling well-controlled experiments. In recent years, these capacities have turned the archerfish into a model animal for studying a variety of visual functions, from visual saliency and visual search, through fast visually guided prediction, and all the way to higher level visual processing such as face recognition. Here we review these recent developments and show how they fall into two emerging lines of research on this animal model. The first is ethologically motivated and emphasizes how the natural environment and habitat of the archerfish interact with its visual processing during predation. The second is driven by parallels to the primate brain and aims to determine whether the latter's characteristic visual information processing capacities can also be found in the qualitatively different fish brain, thereby underscoring the functional universality of certain visual processes. We discuss the differences between these two lines of research and possible future directions.
October 2018
Action and learning shape the activity of neuronal circuits in the visual cortex
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Janelle MP Pakan, Valerio Francioni, Nathalie L Rochefort Nonsensory variables strongly influence neuronal activity in the adult mouse primary visual cortex. Neuronal responses to visual stimuli are modulated by behavioural state, such as arousal and motor activity, and are shaped by experience. This dynamic process leads to neural representations in the visual cortex that reflect stimulus familiarity, expectations of reward and object location, and mismatch between self-motion and visual-flow. The recent development of genetic tools and recording techniques in awake behaving mice has enabled the investigation of the circuit mechanisms underlying state-dependent and experience-dependent neuronal representations in primary visual cortex. These neuronal circuits involve neuromodulatory, top-down cortico-cortical and thalamocortical pathways. The functions of nonsensory signals at this early stage of visual information processing are now beginning to be unravelled.
October 2018
The neural circuits of thermal perception
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Phillip Bokiniec, Niccol
October 2018
The hippocampus in depth: a sublayer-specific perspective of entorhinal–hippocampal function
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Manuel Valero, Liset Menendez de la Prida Understanding how the brain represents events is a fundamental question in neuroscience. The entorhinal–hippocampal system is central to such representations, which are severely compromised in some neurological diseases. In spite of much progress, a comprehensive, integrated view of spatial, temporal and other aspects of episodic representation remains elusive. Here, we review recent data on the role of cell-type specific entorhinal inputs which excite deep and superficial CA1 pyramidal cells by direct and indirect pathways. We discuss how an entorhinal dialogue with deep-superficial CA1 cells can multiplex neuronal activity along theta phases and how their reactivation may be segregated during sharp-wave ripples. Thus, deep and superficial CA1 sublayers provide substrate for general hippocampal function.

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August 2018
Bottom-up and top-down modulation of multisensory integration
Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52 Author(s): Ilsong Choi, Jae-Yun Lee, Seung-Hee Lee Sensory perception in the real world requires proper integration of different modality inputs. Process of multisensory integration is not uniform. It varies from individual to individual and changes at different behavioral states of the animal. What factors affect multisensory integration? How does the mammalian brain reconstruct a multisensory world at different states? Here, we summarize recent findings on bottom-up and top-down factors that can modulate sensory processing and multisensory integration. We discuss cortical circuits that are responsible for modulation of multisensory processing based on recent rodent studies. We suggest that multisensory information is not a simple, fixed signal in the brain. Multisensory processing is dynamically modulated in the mammalian brain and leads to a unique and subjective experience of perception.
August 2018
Towards resolving the presynaptic NMDA receptor debate
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Guy Bouvier, Rylan S Larsen, Antonio Rodr
August 2018
Creating diverse synapses from the same molecules
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Zoltan Nusser Research over the past half a century has revealed remarkable diversity among chemical synapses of the CNS. The structural, functional and molecular diversity of synapses was mainly concluded from studying different synapses in distinct brain regions and preparations. It is not surprising that synapses made by molecularly distinct pre-synaptic and post-synaptic cells display different morphological and functional properties with distinct underlying molecular mechanisms. However, synapses made by a single presynaptic cell onto distinct types of postsynaptic cells, or distinct presynaptic inputs onto a single postsynaptic cell, also show remarkable heterogeneity. Here, by reviewing recent experiments, I suggest that robust functional diversity can be achieved by building synapses from the same molecules, but using different numbers, densities and nanoscale arrangements.
August 2018
Functional implications of inhibitory synapse placement on signal processing in pyramidal neuron dendrites
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Josiah R Boivin, Elly Nedivi A rich literature describes inhibitory innervation of pyramidal neurons in terms of the distinct inhibitory cell types that target the soma, axon initial segment, or dendritic arbor. Less attention has been devoted to how localization of inhibition to specific parts of the pyramidal dendritic arbor influences dendritic signal detection and integration. The effect of inhibitory inputs can vary based on their placement on dendritic spines versus shaft, their distance from the soma, and the branch order of the dendrite they inhabit. Inhibitory synapses are also structurally dynamic, and the implications of these dynamics depend on their dendritic location. Here we consider the heterogeneous roles of inhibitory synapses as defined by their strategic placement on the pyramidal cell dendritic arbor.
August 2018
Local mechanisms regulating selective cargo entry and long-range trafficking in axons
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Laura F Gumy, Casper C Hoogenraad The polarized long-distance transport of neuronal cargoes depends on the presence of functional and structural axonal subcompartments. Given the heterogeneity of neuronal cargoes, selective sorting and entry occurs in the proximal axon where multiple subcellular specializations such as the axon initial segment, the pre-axonal exclusion zone, the MAP2 pre-axonal filtering zone and the Tau diffusion barrier provide different levels of regulation. Cargoes allowed to pass through the proximal axon spread into the more distal parts. Recent findings show that diverse cargo distributions along the axon depend on the compartmentalized organization of the cytoskeleton and the local regulation of multiple motor proteins by microtubule associated proteins. In this review, we focus on the local mechanisms that control cargo motility and discuss how they play a role in the overall circulation of axonal cargoes.
August 2018
Neuronal autophagy and intercellular regulation of homeostasis in the brain
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Aditi Kulkarni, Jessica Chen, Sandra Maday Neurons are particularly dependent on robust quality control pathways to maintain cellular homeostasis and functionality throughout their extended lifetime. Failure to regulate protein and organelle integrity is linked to devastating neurodegenerative diseases. Autophagy is a lysosomal degradation pathway that maintains homeostasis by recycling damaged or aged cellular components. Autophagy has important functions in development of the nervous system, as well as in neuronal function and survival. In fact, defects in autophagy underlie neurodegeneration in mice and humans. Here, we review the compartment-specific dynamics and functions for autophagy in neurons. Emerging evidence suggests novel pathways for the intercellular coordination of quality control pathways between neurons and glia to maintain homeostasis in the brain.
August 2018
Signal propagation along the axon
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Sylvain Rama, Micka
August 2018
Axonal transport and maturation of lysosomes
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Shawn M Ferguson Lysosomes perform degradative functions that are important for all cells. However, neurons are particularly dependent on optimal lysosome function due to their extremes of longevity, size and polarity. Axons in particular exemplify the major spatial challenges faced by neurons in the maintenance of lysosome biogenesis and function. What impact does this have on the regulation and functions of lysosomes in axons? This review focuses on the mechanisms whereby axonal lysosome biogenesis, transport and function are adapted to meet neuronal demand. Important features include the dynamic relationship between endosomes, autophagosomes and lysosomes as well as the transport mechanisms that support the movement of lysosome precursors in axons. A picture is emerging wherein intermediates in the lysosome maturation processes that would only exist transiently within the crowded confines of a neuronal cell body are spatially and temporally separated over the extreme distances encountered in axons. Axons may thus offer significant opportunities for the analysis of the mechanisms that control lysosome biogenesis. Insights from the genetics and pathology of human neurodegenerative diseases furthermore emphasize the importance of efficient axonal transport of lysosomes and their precursors.
August 2018
The electrical significance of axon location diversity
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Maarten HP Kole, Romain Brette The axon initial segment (AIS) is a unique domain of the proximal axon serving critical electrical and structural roles including the initiation of action potentials and maintenance of cellular polarity. Recent experimental and theoretical advances demonstrate that the anatomical site for initiation is remarkably diverse. The AIS location varies not only axially, along the axon, but axons also emerge variably from either the soma or proximal dendrites. Here, we review the evidence that the diversity of AIS and axon location has a substantial impact on the electrical properties and speculate that the anatomical heterogeneity of axon locations expands synaptic integration within cell types and improves information processing in neural circuits.
August 2018
Cytoskeleton dynamics in axon regeneration
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Oriane Blanquie, Frank Bradke Recent years have seen cytoskeleton dynamics emerging as a key player in axon regeneration. The cytoskeleton, in particular microtubules and actin, ensures the growth of neuronal processes and maintains the singular, highly polarized shape of neurons. Following injury, adult central axons are tipped by a dystrophic structure, the retraction bulb, which prevents their regeneration. Abnormal cytoskeleton dynamics are responsible for the formation of this growth-incompetent structure but pharmacologically modulating cytoskeleton dynamics of injured axons can transform this structure into a growth-competent growth cone. The cytoskeleton also drives the migration of scar-forming cells after an injury. Targeting its dynamics modifies the composition of the inhibitory environment formed by scar tissue and renders it more permissive for regenerating axons. Hence, cytoskeleton dynamics represent an appealing target to promote axon regeneration. As some of cytoskeleton-targeting drugs are used in the clinics for other purposes, they hold the promise to be used as a basis for a regenerative therapy after a spinal cord injury.
August 2018
What neurons tell themselves: autocrine signals play essential roles in neuronal development and function
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Kelsey A Herrmann, Heather T Broihier Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies indicate that growth factors also signal via cell-autonomous, or autocrine, mechanisms. Autocrine signals have been discovered in many neuronal contexts, providing insights into their regulation and function. The growing realization of the importance of cell-autonomous signaling stems from advances in both conditional genetic approaches and in sophisticated analyses of growth factor dynamics, which combine to enable rigorous in vivo dissection of signaling pathways. Here we review recent studies defining autocrine roles for growth factors such as BDNF, and classical morphogens, including Wnts and BMPs, in regulating neuronal development and plasticity. Collectively, these studies highlight an intimate relationship between activity-dependent autocrine signaling and synaptic plasticity, and further suggest a common principle for coordinating paracrine and autocrine signaling in the nervous system.
August 2018
Autophagy in the presynaptic compartment
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Patrick L
August 2018
Molecular control of local translation in axon development and maintenance
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Jean-Michel Cioni, Max Koppers, Christine E Holt The tips of axons are often far away from the cell soma where most proteins are synthesized. Recent work has revealed that axonal mRNA transport and localised translation are key regulatory mechanisms that allow these distant outposts of the cell to respond rapidly to extrinsic factors and maintain axonal homeostasis. Here, we review recent evidence pointing to an increasingly broad role for local protein synthesis in controlling axon shape, synaptogenesis and axon survival by regulating diverse cellular processes such as vesicle trafficking, cytoskeletal remodelling and mitochondrial integrity. We further highlight current research on the regulatory mechanisms that coordinate the localization and translation of functionally linked mRNAs in axons.
August 2018
The tubulin code in neuronal polarity
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): James H Park, Antonina Roll-Mecak Cells depend on the asymmetric distribution of their components for homeostasis, differentiation and movement. In no other cell type is this requirement more critical than in the neuron where complex structures are generated during process growth and elaboration and cargo is transported over distances several thousand times the cell body diameter. Microtubules act both as dynamic structural elements and as tracks for intracellular transport. Microtubules are mosaic polymers containing multiple tubulin isoforms functionalized with abundant posttranslational modifications that are asymmetrically distributed in neurons. An increasing body of evidence supports the hypothesis that the combinatorial information expressed through tubulin genetic and chemical diversity controls microtubule dynamics, mechanics and interactions with microtubule effectors and thus constitutes a ‘tubulin code’. Here we give a brief overview of tubulin isoform usage and posttranslational modifications in the neuron, and highlight recent progress in understanding the molecular mechanisms of the tubulin code.
August 2018
Neuronal functions of adaptor complexes involved in protein sorting
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Carlos M Guardia, Raffaella De Pace, Rafael Mattera, Juan S Bonifacino Selective transport of transmembrane proteins to different intracellular compartments often involves the recognition of sorting signals in the cytosolic domains of the proteins by components of membrane coats. Some of these coats have as their key components a family of heterotetrameric adaptor protein (AP) complexes named AP-1 through AP-5. AP complexes play important roles in all cells, but their functions are most critical in neurons because of the extreme compartmental complexity of these cells. Accordingly, various diseases caused by mutations in AP subunit genes exhibit a range of neurological abnormalities as their most salient features. In this article, we discuss the properties of the different AP complexes, with a focus on their roles in neuronal physiology and pathology.
August 2018
Shaping neurodevelopment: distinct contributions of cytoskeletal proteins
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Ngang Heok Tang, Yishi Jin Development of a neuron critically depends on the organization of its cytoskeleton. Cytoskeletal components, such as tubulins and actins, have the remarkable ability to organize themselves into filaments and networks to support specialized and compartmentalized functions. Alterations in cytoskeletal proteins have long been associated with a variety of neurodevelopmental disorders. This review focuses on recent findings, primarily from forward genetic screens in Caenorhabditis elegans that illustrate how different tubulin protein isotypes can play distinct roles in neuronal development and function. Additionally, we discuss studies revealing new regulators of the actin cytoskeleton, and highlight recent technological advances in in vivo imaging and functional dissection of the neuronal cytoskeleton.
August 2018
Presynaptic origins of distinct modes of neurotransmitter release
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Natali L Chanaday, Ege T Kavalali Presynaptic nerve terminals release neurotransmitter synchronously, asynchronously or spontaneously. During synchronous neurotransmission release is precisely coupled to action potentials, in contrast, asynchronous release events show only loose temporal coupling to presynaptic activity whereas spontaneous neurotransmission occurs independent of presynaptic activity. The mechanisms that give rise to this diversity in neurotransmitter release modes are poorly understood. Recent studies have described several presynaptic molecular pathways controlling synaptic vesicle pool segregation and recycling, which in turn may dictate distinct modes of neurotransmitter release. In this article, we review this recent work regarding neurotransmitter release modes and their relationship to synaptic vesicle pool dynamics as well as the molecular machinery that establishes synaptic vesicle pool identity.
August 2018
Importance of the subcellular location of protein deposits in neurodegenerative diseases
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Anne Bertolotti Alzheimer's disease, Parkinson's, Huntington's, amyotrophic lateral sclerosis (ALS) and prion disorders are devastating neurodegenerative diseases of increasing prevalence in aging populations. Although clinically different, they share similar molecular features: the accumulation of one or two proteins in abnormal conformations inside or outside neurons. Enhancing protein quality control systems could be a useful strategy to neutralize the abnormal proteins causing neurodegenerative diseases. This review emphasizes the subcellular location of protein deposits in neurodegenerative diseases and the need to tailor strategies aimed at boosting protein quality control systems to the affected subcellular compartment. Inhibition of a protein phosphatase terminating the unfolded protein response will be discussed as a strategy to protect from diseases associated with misfolded proteins in the endoplasmic reticulum.
August 2018
Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Tara E Tracy, Li Gan The accumulation of pathological tau in the brain is associated with neuronal deterioration and cognitive impairments in tauopathies including Alzheimer's disease. Tau, while primarily localized in the axons of healthy neurons, accumulates in the soma and dendrites of neurons under pathogenic conditions. Tau is found in both presynaptic and postsynaptic compartments of neurons in Alzheimer's disease. New research supports that soluble forms of tau trigger pathophysiology in the brain by altering properties of synaptic and neuronal function at the early stages of disease progression, before neurons die. Here we review the current understanding of how tau-mediated synaptic and neuronal dysfunction contributes to cognitive decline. Delineating the mechanisms by which pathogenic tau alters synapses, dendrites and axons will help lay the foundation for new strategies that can restore neuronal function in tauopathy.
June 2018
Converging cellular themes for the hereditary spastic paraplegias
Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51 Author(s): Craig Blackstone Hereditary spastic paraplegias (HSPs) are neurologic disorders characterized by prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. They are among the most genetically-diverse neurologic disorders, with >80 distinct genetic loci and over 60 identified genes. Studies investigating the molecular pathogenesis underlying HSPs have emphasized the importance of converging cellular pathogenic themes in the most common forms of HSP, providing compelling targets for therapy. Most notably, these include organelle shaping and biogenesis as well as membrane and cargo trafficking.
June 2018
Investigation of brain science and neurological/psychiatric disorders using genetically modified non-human primates
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Hideyuki Okano, Noriyuki Kishi Although mice have been the most frequently used experimental animals in many research fields due to well-established gene manipulation techniques, recent evidence has revealed that rodent models do not always recapitulate pathophysiology of human neurological and psychiatric diseases due to the differences between humans and rodents. The recent developments in gene manipulation of non-human primate have been attracting much attention in the biomedical research field, because non-human primates have more applicable brain structure and function than rodents. In this review, we summarize recent progress on genetically-modified non-human primates including transgenic and knockout animals using genome editing technology.
June 2018
Neural lineage tracing in the mammalian brain
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Jian Ma, Zhongfu Shen, Yong-Chun Yu, Song-Hai Shi Delineating the lineage of neural cells that captures the progressive steps in their specification is fundamental to understanding brain development, organization, and function. Since the earliest days of embryology, lineage questions have been addressed with methods of increasing specificity, capacity, and resolution. Yet, a full realization of individual cell lineages remains challenging for complex systems. A recent explosion of technical advances in genome-editing and single-cell sequencing has enabled lineage analysis in an unprecedented scale, speed, and depth across different species. In this review, we discuss the application of available as well as future genetic labeling techniques for tracking neural lineages in vivo in the mammalian nervous system.
June 2018
Proximity labeling: spatially resolved proteomic mapping for neurobiology
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Shuo Han, Jiefu Li, Alice Y Ting Understanding signaling pathways in neuroscience requires high-resolution maps of the underlying protein networks. Proximity-dependent biotinylation with engineered enzymes, in combination with mass spectrometry-based quantitative proteomics, has emerged as a powerful method to dissect molecular interactions and the localizations of endogenous proteins. Recent applications to neuroscience have provided insights into the composition of sub-synaptic structures, including the synaptic cleft and inhibitory post-synaptic density. Here we compare the different enzymes and small-molecule probes for proximity labeling in the context of cultured neurons and tissue, review existing studies, and provide technical suggestions for the in vivo application of proximity labeling.
June 2018
Genetic strategies to tackle neurological diseases in fruit flies
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): M
June 2018
Mesh electronics: a new paradigm for tissue-like brain probes
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Guosong Hong, Xiao Yang, Tao Zhou, Charles M Lieber Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to ‘look and behave’ like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies.
June 2018
Implantable, wireless device platforms for neuroscience research
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Philipp Gutruf, John A Rogers Recently developed classes of ultraminiaturized wireless devices provide powerful capabilities in neuroscience research, as implantable light sources for simulation/inhibition via optogenetics, as integrated microfluidic systems for programmed pharmacological delivery and as multimodal sensors for physiological measurements. These platforms leverage basic advances in biocompatible materials, semiconductor device designs and systems engineering concepts to afford modes of operation that are qualitatively distinct from those of conventional approaches that tether animals to external hardware by means of optical fibers, electrical cables and/or fluidic tubing. Neuroscience studies that exploit the unique features of these technologies enable insights into neural function through targeted stimulation, inhibition and recording, with spatially and genetically precise manipulation of neural circuit activity. Experimental possibilities include studies in naturalistic, three dimensional environments, investigations of pair-wise or group related social interactions and many other scenarios of interest that cannot be addressed using traditional hardware.
June 2018
Nanomaterials at the neural interface
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Denis Scaini, Laura Ballerini Interfacing the nervous system with devices able to efficiently record or modulate the electrical activity of neuronal cells represents the underlying foundation of future theranostic applications in neurology and of current openings in neuroscience research. These devices, usually sensing cell activity via microelectrodes, should be characterized by safe working conditions in the biological milieu together with a well-controlled operation-life. The stable device/neuronal electrical coupling at the interface requires tight interactions between the electrode surface and the cell membrane. This neuro-electrode hybrid represents the hyphen between the soft nature of neural tissue, generating electrical signals via ion motions, and the rigid realm of microelectronics and medical devices, dealing with electrons in motion. Efficient integration of these entities is essential for monitoring, analyzing and controlling neuronal signaling but poses significant technological challenges. Improving the cell/electrode interaction and thus the interface performance requires novel engineering of (nano)materials: tuning at the nanoscale electrode's properties may lead to engineer interfacing probes that better camouflaged with their biological target. In this brief review, we highlight the most recent concepts in nanotechnologies and nanomaterials that might help reducing the mismatch between tissue and electrode, focusing on the device's mechanical properties and its biological integration with the tissue.

Expansion microscopy: development and neuroscience applications
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50 Author(s): Emmanouil D Karagiannis, Edward S Boyden Many neuroscience questions center around understanding how the molecules and wiring in neural circuits mechanistically yield behavioral functions, or go awry in disease states. However, mapping the molecules and wiring of neurons across the large scales of neural circuits has posed a great challenge. We recently developed expansion microscopy (ExM), a process in which we physically magnify biological specimens such as brain circuits. We synthesize throughout preserved brain specimens a dense, even mesh of a swellable polymer such as sodium polyacrylate, anchoring key biomolecules such as proteins and nucleic acids to the polymer. After mechanical homogenization of the specimen-polymer composite, we add water, and the polymer swells, pulling biomolecules apart. Due to the larger separation between molecules, ordinary microscopes can then perform nanoscale resolution imaging. We here review the ExM technology as well as applications to the mapping of synapses, cells, and circuits, including deployment in species such as Drosophila, mouse, non-human primate, and human.
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