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Progress and remaining challenges in high-throughput volume electron microscopy.
Abstract Recent advances in the effectiveness of the automatic extraction of neural circuits from volume electron microscopy data have made us more optimistic that the goal of reconstructing the nervous system of an entire adult mammal (or bird) brain can be achieved in the next decade. The progress on the data analysis side-based mostly on variants of convolutional neural networks-has been particularly impressive, but improvements in the quality and spatial extent of published VEM datasets are substantial. Methodologically, the combination of hot-knife sample partitioning and ion milling stands out as a conceptua...
Source: Current Opinion in Neurobiology - May 11, 2018 Category: Neurology Authors: Kornfeld J, Denk W Tags: Curr Opin Neurobiol Source Type: research

Editorial overview: Neurotechnologies.
PMID: 29754872 [PubMed - as supplied by publisher] (Source: Current Opinion in Neurobiology)
Source: Current Opinion in Neurobiology - May 10, 2018 Category: Neurology Authors: Anikeeva P, Luo L Tags: Curr Opin Neurobiol Source Type: research

Converging cellular themes for the hereditary spastic paraplegias.
Abstract 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 a...
Source: Current Opinion in Neurobiology - May 10, 2018 Category: Neurology Authors: Blackstone C Tags: Curr Opin Neurobiol Source Type: research

Magnetic Resonance Imaging technology-bridging the gap between noninvasive human imaging and optical microscopy.
Abstract Technological advances in Magnetic Resonance Imaging (MRI) have provided substantial gains in the sensitivity and specificity of functional neuroimaging. Mounting evidence demonstrates that the hemodynamic changes utilized in functional MRI can be far more spatially and thus neuronally specific than previously believed. This has motivated a push toward novel, high-resolution MR imaging strategies that can match this biological resolution limit while recording from the entire human brain. Although sensitivity increases are a necessary component, new MR encoding technologies are required to convert improved...
Source: Current Opinion in Neurobiology - May 10, 2018 Category: Neurology Authors: Polimeni JR, Wald LL Tags: Curr Opin Neurobiol Source Type: research

Constraints on somatosensory map development: mutants lead the way.
Abstract 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...
Source: Current Opinion in Neurobiology - May 9, 2018 Category: Neurology Authors: Gaspar P, Renier N Tags: Curr Opin Neurobiol Source Type: research

Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease.
Abstract 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. He...
Source: Current Opinion in Neurobiology - May 9, 2018 Category: Neurology Authors: Tracy TE, Gan L Tags: Curr Opin Neurobiol Source Type: research

Single cell transcriptomics in neuroscience: cell classification and beyond.
Abstract Biology has been facing a daunting problem since the cell was understood to be the building block of metazoans: how do we study multicellular systems, when a universal approach to characterize their building blocks and classify them does not exist? Metazoan diversity has not helped: there are many model and non-model organisms, developmental and adult stages, healthy and diseased states. Here, I review the application of single cell transcriptomics to cell classification in neuroscience and its corollaries: the differentially expressed genes discovered in this process are a treasure trove for understandin...
Source: Current Opinion in Neurobiology - May 5, 2018 Category: Neurology Authors: Tasic B Tags: Curr Opin Neurobiol Source Type: research

Development of the whisker-to-barrel cortex system.
HJ Abstract This review provides an overview on the development of the rodent whisker-to-barrel cortex system from late embryonic stage to the end of the first postnatal month. During this period the system shows a remarkable transition from a mostly genetic-molecular driven generation of crude connectivity, providing the template for activity-dependent structural and functional maturation and plasticity, to the manifestation of a complex behavioral repertoire including social interactions. Spontaneous and sensory-evoked activity is present in neonatal barrel cortex and control the generation of the cortical arch...
Source: Current Opinion in Neurobiology - May 5, 2018 Category: Neurology Authors: Yang JW, Kilb W, Kirischuk S, Unichenko P, Stüttgen MC, Luhmann HJ Tags: Curr Opin Neurobiol Source Type: research

Cortical developmental death: selected to survive or fated to die.
Abstract The mature cerebral cortex only contains a fraction of the cells that are generated during embryonic development. Indeed some neuronal populations are produced in excess and later subjected to partial elimination whereas others are almost completely removed during the first two postnatal weeks in mice. Although the identity of cells that disappear, the time course and mechanisms of their death are becoming reasonably well established, the meaning of producing supernumerary cells still remains elusive. In this review, we focus on recent data that shed a new light on the mechanisms involved in adjusting cel...
Source: Current Opinion in Neurobiology - May 5, 2018 Category: Neurology Authors: Causeret F, Coppola E, Pierani A Tags: Curr Opin Neurobiol Source Type: research

The neural circuits of thermal perception.
Abstract Thermal information about skin surface temperature is a key sense for the perception of object identity and valence. The identification of ion channels involved in the transduction of thermal changes has provided a genetic access point to the thermal system. However, from sensory specific 'labeled-lines' to multimodal interactive pathways, the functional organization and identity of the neural circuits mediating innocuous thermal perception have been debated for over 100 years. Here we highlight points in the system that require further attention and review recent advances using in vivo electrophysiology,...
Source: Current Opinion in Neurobiology - May 4, 2018 Category: Neurology Authors: Bokiniec P, Zampieri N, Lewin GR, Poulet JF Tags: Curr Opin Neurobiol Source Type: research

Origin and circuitry of spinal locomotor interneurons generating different speeds.
Abstract 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 co...
Source: Current Opinion in Neurobiology - May 3, 2018 Category: Neurology Authors: Boije H, Kullander K Tags: Curr Opin Neurobiol Source Type: research

Experience-dependent plasticity in the lateral geniculate nucleus.
Abstract 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. ...
Source: Current Opinion in Neurobiology - May 3, 2018 Category: Neurology Authors: Rose T, Bonhoeffer T Tags: Curr Opin Neurobiol Source Type: research

The hippocampus in depth: a sublayer-specific perspective of entorhinal-hippocampal function.
Abstract 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 multipl...
Source: Current Opinion in Neurobiology - May 2, 2018 Category: Neurology Authors: Valero M, de la Prida LM Tags: Curr Opin Neurobiol Source Type: research

What a predator can teach us about visual processing: a lesson from the archerfish.
Abstract 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 lev...
Source: Current Opinion in Neurobiology - May 1, 2018 Category: Neurology Authors: Ben-Tov M, Ben-Shahar O, Segev R Tags: Curr Opin Neurobiol Source Type: research

Action and learning shape the activity of neuronal circuits in the visual cortex.
Abstract 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...
Source: Current Opinion in Neurobiology - May 1, 2018 Category: Neurology Authors: Pakan JM, Francioni V, Rochefort NL Tags: Curr Opin Neurobiol Source Type: research

Thalamocortical function in developing sensory circuits.
Abstract 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 se...
Source: Current Opinion in Neurobiology - April 28, 2018 Category: Neurology Authors: Colonnese MT, Phillips MA Tags: Curr Opin Neurobiol Source Type: research

Neural encoding of sensory and behavioral complexity in the auditory cortex.
Abstract 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 ...
Source: Current Opinion in Neurobiology - April 27, 2018 Category: Neurology Authors: Kuchibhotla K, Bathellier B Tags: Curr Opin Neurobiol Source Type: research

Memory circuits: CA2.
Abstract 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...
Source: Current Opinion in Neurobiology - April 26, 2018 Category: Neurology Authors: Piskorowski RA, Chevaleyre V Tags: Curr Opin Neurobiol Source Type: research

Neuronal coding mechanisms mediating fear behavior.
Abstract 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 understa...
Source: Current Opinion in Neurobiology - April 26, 2018 Category: Neurology Authors: Rozeske RR, Herry C Tags: Curr Opin Neurobiol Source Type: research

Molecular diversity underlying cortical excitatory and inhibitory synapse development.
Abstract 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 t...
Source: Current Opinion in Neurobiology - April 25, 2018 Category: Neurology Authors: Favuzzi E, Rico B Tags: Curr Opin Neurobiol Source Type: research

Developmental interactions between thalamus and cortex: a true love reciprocal story.
ute;pez-Bendito G Abstract The developmental programs that control the specification of cortical and thalamic territories are maintained largely as independent processes. However, bulk of evidence demonstrates the requirement of the reciprocal interactions between cortical and thalamic neurons as key for the correct development of functional thalamocortical circuits. This reciprocal loop of connections is essential for sensory processing as well as for the execution of complex sensory-motor tasks. Here, we review recent advances in our understanding of how mutual collaborations between both brain regions define ar...
Source: Current Opinion in Neurobiology - April 25, 2018 Category: Neurology Authors: Antón-Bolaños N, Espinosa A, López-Bendito G Tags: Curr Opin Neurobiol Source Type: research

Personalized brain network models for assessing structure-function relationships.
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. PMID: 29704749 [PubMed - as supplied by publisher] (Source: Current Opinion in Neurobiology)
Source: Current Opinion in Neurobiology - April 25, 2018 Category: Neurology Authors: Bansal K, Nakuci J, Muldoon SF Tags: Curr Opin Neurobiol Source Type: research

Active mechanosensory feedback during locomotion in the zebrafish spinal cord.
Abstract 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 fas...
Source: Current Opinion in Neurobiology - April 25, 2018 Category: Neurology Authors: Knafo S, Wyart C Tags: Curr Opin Neurobiol Source Type: research

Neural and genetic basis of dexterous hand movements.
Abstract 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 ...
Source: Current Opinion in Neurobiology - April 23, 2018 Category: Neurology Authors: Yoshida Y, Isa T Tags: Curr Opin Neurobiol Source Type: research

Socio-sexual processing in cortical circuits.
Abstract 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 f...
Source: Current Opinion in Neurobiology - April 22, 2018 Category: Neurology Authors: Brecht M, Lenschow C, Rao RP Tags: Curr Opin Neurobiol Source Type: research

Behavioral readout of spatio-temporal codes in olfaction.
Abstract 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 testin...
Source: Current Opinion in Neurobiology - April 22, 2018 Category: Neurology Authors: Chong E, Rinberg D Tags: Curr Opin Neurobiol Source Type: research

Vestibular signals in primate cortex for self-motion perception.
Abstract 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 robus...
Source: Current Opinion in Neurobiology - April 21, 2018 Category: Neurology Authors: Gu Y Tags: Curr Opin Neurobiol Source Type: research

Transcription factor mechanisms guiding motor neuron differentiation and diversification.
Abstract 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 unprecedent...
Source: Current Opinion in Neurobiology - April 21, 2018 Category: Neurology Authors: Cave C, Sockanathan S Tags: Curr Opin Neurobiol Source Type: research

Ultrasonic modulation of neural circuit activity.
Abstract Ultrasound (US) is recognized for its use in medical imaging as a diagnostic tool. As an acoustic energy source, US has become increasingly appreciated over the past decade for its ability to non-invasively modulate cellular activity including neuronal activity. Data obtained from a host of experimental models has shown that low-intensity US can reversibly modulate the physiological activity of neurons in peripheral nerves, spinal cord, and intact brain circuits. Experimental evidence indicates that acoustic pressures exerted by US act, in part, on mechanosensitive ion channels to modulate activity. While...
Source: Current Opinion in Neurobiology - April 16, 2018 Category: Neurology Authors: Tyler WJ, Lani SW, Hwang GM Tags: Curr Opin Neurobiol Source Type: research

Holographic imaging and photostimulation of neural activity.
Abstract Optical imaging methods are powerful tools in neuroscience as they can systematically monitor the activity of neuronal populations with high spatiotemporal resolution using calcium or voltage indicators. Moreover, caged compounds and optogenetic actuators enable to optically manipulate neural activity. Among optical methods, computer-generated holography offers an enormous flexibility to sculpt the excitation light in three-dimensions (3D), particularly when combined with two-photon light sources. By projecting holographic light patterns on the sample, the activity of multiple neurons across a 3D brain vo...
Source: Current Opinion in Neurobiology - April 13, 2018 Category: Neurology Authors: Yang W, Yuste R Tags: Curr Opin Neurobiol Source Type: research

Probing the brain with molecular fMRI.
Abstract One of the greatest challenges of modern neuroscience is to incorporate our growing knowledge of molecular and cellular-scale physiology into integrated, organismic-scale models of brain function in behavior and cognition. Molecular-level functional magnetic resonance imaging (molecular fMRI) is a new technology that can help bridge these scales by mapping defined microscopic phenomena over large, optically inaccessible regions of the living brain. In this review, we explain how MRI-detectable imaging probes can be used to sensitize noninvasive imaging to mechanistically significant components of neural p...
Source: Current Opinion in Neurobiology - April 9, 2018 Category: Neurology Authors: Ghosh S, Harvey P, Simon JC, Jasanoff A Tags: Curr Opin Neurobiol Source Type: research

High-speed 3D imaging of cellular activity in the brain using axially-extended beams and light sheets.
This article describes these approaches and presents a simple model that demonstrates key advantages of axially-extended illumination over point-scanning strategies for high-speed volumetric imaging, including longer integration times per voxel, improved photon efficiency and reduced photodamage. PMID: 29642044 [PubMed - as supplied by publisher] (Source: Current Opinion in Neurobiology)
Source: Current Opinion in Neurobiology - April 7, 2018 Category: Neurology Authors: Hillman EM, Voleti V, Patel K, Li W, Yu H, Perez-Campos C, Benezra SE, Bruno RM, Galwaduge PT Tags: Curr Opin Neurobiol Source Type: research

Towards circuit optogenetics.
Abstract Optogenetics neuronal targeting combined with single-photon wide-field illumination has already proved its enormous potential in neuroscience, enabling the optical control of entire neuronal networks and disentangling their role in the control of specific behaviors. However, establishing how a single or a sub-set of neurons controls a specific behavior, or how functionally identical neurons are connected in a particular task, or yet how behaviors can be modified in real-time by the complex wiring diagram of neuronal connections requires more sophisticated approaches enabling to drive neuronal circuits act...
Source: Current Opinion in Neurobiology - April 6, 2018 Category: Neurology Authors: Chen IW, Papagiakoumou E, Emiliani V Tags: Curr Opin Neurobiol Source Type: research

Importance of the subcellular location of protein deposits in neurodegenerative diseases.
Abstract 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 ...
Source: Current Opinion in Neurobiology - April 6, 2018 Category: Neurology Authors: Bertolotti A Tags: Curr Opin Neurobiol Source Type: research

Lighting up the brain: genetically encoded fluorescent sensors for imaging neurotransmitters and neuromodulators.
Abstract Measuring the precise dynamics of specific neurotransmitters and neuromodulators in the brain is essential for understanding how information is transmitted and processed. Thanks to the development and optimization of various genetically encoded sensors, we are approaching the stage in which a few key neurotransmitters/neuromodulators can be imaged with high cell specificity and good signal-to-noise ratio. Here, we summarize recent progress regarding these sensors, focusing on their design principles, properties, potential applications, and current limitations. We also highlight the G protein-coupled recep...
Source: Current Opinion in Neurobiology - April 5, 2018 Category: Neurology Authors: Wang H, Jing M, Li Y Tags: Curr Opin Neurobiol Source Type: research

Engineered viral vectors for functional interrogation, deconvolution, and manipulation of neural circuits.
Abstract Optimization of traditional replication-competent viral tracers has granted access to immediate synaptic partners of target neuronal populations, enabling the dissection of complex brain circuits into functional neural pathways. The excessive virulence of most conventional tracers, however, impedes their utility in revealing and genetically perturbing cellular function on long time scales. As a promising alternative, the natural capacity of adeno-associated viral (AAV) vectors to safely mediate persistent and robust gene expression has stimulated strong interest in adapting them for sparse neuronal labeli...
Source: Current Opinion in Neurobiology - March 31, 2018 Category: Neurology Authors: Sun S, Schaffer DV Tags: Curr Opin Neurobiol Source Type: research

Presynaptic origins of distinct modes of neurotransmitter release.
Abstract 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 i...
Source: Current Opinion in Neurobiology - March 26, 2018 Category: Neurology Authors: Chanaday NL, Kavalali ET Tags: Curr Opin Neurobiol Source Type: research

Mesoscale connectomics.
Abstract Brain cells communicate with one another via local and long-range synaptic connections. Structural connectivity is the foundation for neural function. Brain-wide connectivity can be described at macroscopic, mesoscopic and microscopic levels. The mesoscale connectome represents connections between neuronal types across different brain regions. Building a mesoscale connectome requires a detailed understanding of the cell type composition of different brain regions and the patterns of inputs and outputs that each of these cell types receives and forms, respectively. In this review, I discuss historical and ...
Source: Current Opinion in Neurobiology - March 23, 2018 Category: Neurology Authors: Zeng H Tags: Curr Opin Neurobiol Source Type: research

Shaping neurodevelopment: distinct contributions of cytoskeletal proteins.
Abstract 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. Additi...
Source: Current Opinion in Neurobiology - March 22, 2018 Category: Neurology Authors: Tang NH, Jin Y Tags: Curr Opin Neurobiol Source Type: research

Neuronal functions of adaptor complexes involved in protein sorting.
Abstract 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 abnor...
Source: Current Opinion in Neurobiology - March 17, 2018 Category: Neurology Authors: Guardia CM, De Pace R, Mattera R, Bonifacino JS Tags: Curr Opin Neurobiol Source Type: research

The tubulin code in neuronal polarity.
Abstract 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...
Source: Current Opinion in Neurobiology - March 16, 2018 Category: Neurology Authors: Park JH, Roll-Mecak A Tags: Curr Opin Neurobiol Source Type: research

Autophagy in the presynaptic compartment.
dtner M Abstract Regulated release of neurotransmitter depends on the orchestrated function of a large number of proteins in the presynaptic compartment. When synaptic vesicles fuse with the plasma membrane, these membranes and the attached proteins are endocytosed and either recycled or degraded. This turnover needs to be tightly regulated in a timely and spatially confined manner. Increasing evidence suggests that these mechanisms do not only serve for the removal of defective synaptic vesicles or structural proteins of the active zone but also contribute to pathways regulating synaptic strength. The correspondi...
Source: Current Opinion in Neurobiology - March 14, 2018 Category: Neurology Authors: Lüningschrör P, Sendtner M Tags: Curr Opin Neurobiol Source Type: research

Molecular control of local translation in axon development and maintenance.
Abstract 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 furthe...
Source: Current Opinion in Neurobiology - March 14, 2018 Category: Neurology Authors: Cioni JM, Koppers M, Holt CE Tags: Curr Opin Neurobiol Source Type: research

What neurons tell themselves: autocrine signals play essential roles in neuronal development and function.
Abstract 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 disse...
Source: Current Opinion in Neurobiology - March 13, 2018 Category: Neurology Authors: Herrmann KA, Broihier HT Tags: Curr Opin Neurobiol Source Type: research

Cytoskeleton dynamics in axon regeneration.
Abstract 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 g...
Source: Current Opinion in Neurobiology - March 12, 2018 Category: Neurology Authors: Blanquie O, Bradke F Tags: Curr Opin Neurobiol Source Type: research

The electrical significance of axon location diversity.
Abstract 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 anato...
Source: Current Opinion in Neurobiology - March 10, 2018 Category: Neurology Authors: Kole MH, Brette R Tags: Curr Opin Neurobiol Source Type: research

Neuronal autophagy and intercellular regulation of homeostasis in the brain.
Abstract 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-s...
Source: Current Opinion in Neurobiology - March 9, 2018 Category: Neurology Authors: Kulkarni A, Chen J, Maday S Tags: Curr Opin Neurobiol Source Type: research

Axonal transport and maturation of lysosomes.
Abstract 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 en...
Source: Current Opinion in Neurobiology - March 9, 2018 Category: Neurology Authors: Ferguson SM Tags: Curr Opin Neurobiol Source Type: research

Melancholy, anhedonia, apathy: the search for separable behaviors and neural circuits in depression.
Abstract Major depressive disorder can manifest as different combinations of symptoms, ranging from a profound and incapacitating sadness, to a loss of interest in daily life, to an inability to engage in effortful, goal-directed behavior. Recent research has focused on defining the neural circuits that mediate separable features of depression in patients and preclinical animal models, and connections between frontal cortex and brainstem neuromodulators have emerged as candidate targets. The development of methods permitting recording and manipulation of neural circuits defined by connectivity has enabled the inve...
Source: Current Opinion in Neurobiology - March 9, 2018 Category: Neurology Authors: Post RJ, Warden MR Tags: Curr Opin Neurobiol Source Type: research

Editorial overview: Neurobiology of behavior.
PMID: 29526385 [PubMed - as supplied by publisher] (Source: Current Opinion in Neurobiology)
Source: Current Opinion in Neurobiology - March 8, 2018 Category: Neurology Authors: Tye KM, Uchida N Tags: Curr Opin Neurobiol Source Type: research