Location, location, location: nuclear structure regulates gene expression in neurons.
Abstract Genome architecture plays a critical role in regulating the expression of genes that are essential for nervous system development. During neuronal differentiation, spatially and temporally regulated transcription allows neuronal migration, the growth of dendrites and axons, and at later stages, synaptic formation and the establishment of neuronal circuitry. Genome topology and relocation of gene loci within the nucleus are now regarded as key factors that contribute to transcriptional regulation. Here, we review recent work supporting the hypothesis that the dynamic organization of chromatin within the nu...
Source: Current Opinion in Neurobiology - April 18, 2019 Category: Neurology Authors: Brookes E, Riccio A Tags: Curr Opin Neurobiol Source Type: research

Principles of progenitor temporal patterning in the developing invertebrate and vertebrate nervous system.
Abstract During the development of the central nervous system, progenitors successively generate distinct types of neurons which assemble into the circuits that underlie our ability to interact with the environment. Spatial and temporal patterning mechanisms are partially evolutionarily conserved processes that allow generation of neuronal diversity from a limited set of progenitors. Here, we review examples of temporal patterning in neuronal progenitors in the Drosophila ventral nerve cord and in the mammalian cerebral cortex. We discuss cell-autonomous mechanisms and environmental influences on the temporal tran...
Source: Current Opinion in Neurobiology - April 15, 2019 Category: Neurology Authors: Oberst P, Agirman G, Jabaudon D Tags: Curr Opin Neurobiol Source Type: research

Machine learning and big data in psychiatry: toward clinical applications.
Abstract Psychiatry is a medical field concerned with the treatment of mental illness. Psychiatric disorders broadly relate to higher functions of the brain, and as such are richly intertwined with social, cultural, and experiential factors. This makes them exquisitely complex phenomena that depend on and interact with a large number of variables. Computational psychiatry provides two ways of approaching this complexity. Theory-driven computational approaches employ mechanistic models to make explicit hypotheses at multiple levels of analysis. Data-driven machine-learning approaches can make predictions from high-...
Source: Current Opinion in Neurobiology - April 15, 2019 Category: Neurology Authors: Rutledge RB, Chekroud AM, Huys QJ Tags: Curr Opin Neurobiol Source Type: research

Control of neural development and function by glial neuroligins.
Abstract Neuroligins are a family of cell adhesion molecules, which are best known for their functions as postsynaptic components of the trans-synaptic neurexin-neuroligin complexes. Neuroligins are highly conserved across evolution with important roles in the formation, maturation and function of synaptic structures. Mutations in the genes that encode for neuroligins have been linked to a number of neurodevelopmental disorders such as autism and schizophrenia, which stem from synaptic pathologies. Owing to their essential functions in regulating synaptic connectivity and their link to synaptic dysfunction in dise...
Source: Current Opinion in Neurobiology - April 13, 2019 Category: Neurology Authors: Sakers K, Eroglu C Tags: Curr Opin Neurobiol Source Type: research

Synaptogenic pathways.
Abstract During synaptogenesis, presynaptic and postsynaptic assembly are driven by diverse molecular mechanisms, mediated by intrinsic as well as extrinsic factors. How these processes are initiated and coordinated are open questions. Synapse specificity, or synaptic partner selection, is widely understood to be determined by the trans-synaptic binding of cell adhesion molecules. However, in vivo evidence that cell adhesion molecules subsequently function to initiate synapse assembly, as initially proposed, is lacking. Here, we present a summary of our current understanding of synaptogenic pathways that mediate p...
Source: Current Opinion in Neurobiology - April 12, 2019 Category: Neurology Authors: Kurshan PT, Shen K Tags: Curr Opin Neurobiol Source Type: research

Cell type and circuit modules in the spinal cord.
Abstract The spinal cord contains an extraordinarily diverse population of interconnected neurons to process somatosensory information and execute movement. Studies of the embryonic spinal cord have elucidated basic principles underlying the specification of spinal cord neurons, while adult and postnatal studies have provided insight into cell type function and circuitry. However, the overarching principles that bridge molecularly defined subtypes with their connectivity, physiology, and function remain unclear. This review consolidates recent work in spinal neuron characterization, examining how molecular and spa...
Source: Current Opinion in Neurobiology - April 4, 2019 Category: Neurology Authors: Osseward PJ, Pfaff SL Tags: Curr Opin Neurobiol Source Type: research

Neuronal diversity in the somatosensory system: bridging the gap between cell type and function.
Abstract A recent flurry of genetic studies in mice have provided key insights into how the somatosensory system is organized at a cellular level to encode itch, pain, temperature, and touch. These studies are largely predicated on the idea that functional cell types can be identified by their unique developmental provenance and gene expression profile. However, the extent to which gene expression profiles can be correlated with functional cell types and circuit organization remains an open question. In this review, we focus on recent progress in characterizing the sensory afferent and dorsal horn neuron cell type...
Source: Current Opinion in Neurobiology - April 3, 2019 Category: Neurology Authors: Gatto G, Smith KM, Ross SE, Goulding M Tags: Curr Opin Neurobiol Source Type: research

The neural and cognitive architecture for learning from a small sample.
Abstract Artificial intelligence algorithms are capable of fantastic exploits, yet they are still grossly inefficient compared with the brain's ability to learn from few exemplars or solve problems that have not been explicitly defined. What is the secret that the evolution of human intelligence has unlocked? Generalization is one answer, but there is more to it. The brain does not directly solve difficult problems, it is able to recast them into new and more tractable problems. Here, we propose a model whereby higher cognitive functions profoundly interact with reinforcement learning to drastically reduce the deg...
Source: Current Opinion in Neurobiology - April 3, 2019 Category: Neurology Authors: Cortese A, De Martino B, Kawato M Tags: Curr Opin Neurobiol Source Type: research

Towards neural co-processors for the brain: combining decoding and encoding in brain-computer interfaces.
Abstract The field of brain-computer interfaces is poised to advance from the traditional goal of controlling prosthetic devices using brain signals to combining neural decoding and encoding within a single neuroprosthetic device. Such a device acts as a 'co-processor' for the brain, with applications ranging from inducing Hebbian plasticity for rehabilitation after brain injury to reanimating paralyzed limbs and enhancing memory. We review recent progress in simultaneous decoding and encoding for closed-loop control and plasticity induction. To address the challenge of multi-channel decoding and encoding, we intr...
Source: Current Opinion in Neurobiology - April 3, 2019 Category: Neurology Authors: Rao RP Tags: Curr Opin Neurobiol Source Type: research

Deep neural network models of sensory systems: windows onto the role of task constraints.
Abstract Sensory neuroscience aims to build models that predict neural responses and perceptual behaviors, and that provide insight into the principles that give rise to them. For decades, artificial neural networks trained to perform perceptual tasks have attracted interest as potential models of neural computation. Only recently, however, have such systems begun to perform at human levels on some real-world tasks. The recent engineering successes of deep learning have led to renewed interest in artificial neural networks as models of the brain. Here we review applications of deep learning to sensory neuroscience...
Source: Current Opinion in Neurobiology - March 15, 2019 Category: Neurology Authors: Kell AJ, McDermott JH Tags: Curr Opin Neurobiol Source Type: research

Generative models and abstractions for large-scale neuroanatomy datasets.
Abstract Neural datasets are increasing rapidly in both resolution and volume. In neuroanatomy, this trend has been accelerated by innovations in imaging technology. As full datasets are impractical and unnecessary for many applications, it is important to identify abstractions that distill useful features of neural structure, organization, and anatomy. In this review article, we discuss several such abstractions and highlight recent algorithmic advances in working with these models. In particular, we discuss the use of generative models in neuroanatomy; such models may be considered 'meta-abstractions' that captu...
Source: Current Opinion in Neurobiology - March 14, 2019 Category: Neurology Authors: Rolnick D, Dyer EL Tags: Curr Opin Neurobiol Source Type: research

Histone demethylases in neuronal differentiation, plasticity, and disease.
Abstract For more than 40 years after its discovery, histone methylation was thought to be largely irreversible. However, the first histone demethylase (HDM) was identified in 2004, challenging this notion. Since that time, more than 20 HDMs have been identified and characterized, and many have been shown to have critical roles in organismal development, cell fate, and disease. Here, we highlight some of the recent advances in our understanding of the function of HDMs in the context of neuronal development, plasticity, and disease. We focus, in particular, on molecular genetic studies of LSD1, Kdm6b, and Kdm5c tha...
Source: Current Opinion in Neurobiology - March 14, 2019 Category: Neurology Authors: Swahari V, West AE Tags: Curr Opin Neurobiol Source Type: research

Towards the neural population doctrine.
Abstract Across neuroscience, large-scale data recording and population-level analysis methods have experienced explosive growth. While the underlying hardware and computational techniques have been well reviewed, we focus here on the novel science that these technologies have enabled. We detail four areas of the field where the joint analysis of neural populations has significantly furthered our understanding of computation in the brain: correlated variability, decoding, neural dynamics, and artificial neural networks. Together, these findings suggest an exciting trend towards a new era where neural populations a...
Source: Current Opinion in Neurobiology - March 13, 2019 Category: Neurology Authors: Saxena S, Cunningham JP Tags: Curr Opin Neurobiol Source Type: research

Powerhouse of the mind: mitochondrial plasticity at the synapse.
Abstract Neurons are highly polarized cells with extraordinary energy demands, which are mainly fulfilled by mitochondria. In response to altered neuronal energy state, mitochondria adapt to enable energy homeostasis and nervous system function. This adaptation, also called mitochondrial plasticity, can be observed as alterations in the form, function and position. The primary site of energy consumption in neurons is localized at the synapse, where mitochondria are critical for both pre- and postsynaptic functions. In this review, we will discuss molecular mechanisms regulating mitochondrial plasticity at the syna...
Source: Current Opinion in Neurobiology - March 12, 2019 Category: Neurology Authors: Rossi MJ, Pekkurnaz G Tags: Curr Opin Neurobiol Source Type: research

What does the mind learn? A comparison of human and machine learning representations.
We present a brief review of modern machine learning techniques and their use in models of human mental representations, detailing three notable branches: spatial methods, logical methods and artificial neural networks. Each of these branches contains an extensive set of systems, and demonstrate accurate emulations of human learning of categories, concepts and language, despite substantial differences in operation. We suggest that continued applications will allow cognitive researchers the ability to model the complex real-world problems where machine learning has recently been successful, providing more complete behaviour...
Source: Current Opinion in Neurobiology - March 11, 2019 Category: Neurology Authors: Spicer J, Sanborn AN Tags: Curr Opin Neurobiol Source Type: research

Local translation in neuronal processes.
Abstract Neurons exhibit a unique degree of spatial compartmentalization and are able to maintain and remodel their proteomes independently from the cell body. While much effort has been devoted to understanding the capacity and role for local protein synthesis in dendrites and spines, local mRNA translation in mature axons, projecting over distances up to a meter, has received much less attention. Also, little is known about the spatio-temporal dynamics of axonal and dendritic gene expression as function of mRNA abundance, protein synthesis and degradation. Here, we summarize key recent findings that have shaped ...
Source: Current Opinion in Neurobiology - March 9, 2019 Category: Neurology Authors: Biever A, Donlin-Asp PG, Schuman EM Tags: Curr Opin Neurobiol Source Type: research

CBP/p300 in brain development and plasticity: disentangling the KAT's cradle.
Abstract The paralogous transcriptional co-activators CBP and p300 (aka KAT3A and KAT3B, respectively) contain a characteristic and promiscuous lysine acetyltransferase (KAT) domain and multiple independent protein-binding domains that enable them to interact with hundreds of proteins, possibly promoting the acetylation of thousands of target lysine residues. Both proteins play critical roles during the development of the nervous system and may also regulate stimuli-driven transcription and plasticity in postmitotic neurons. The multiplicity of functions, substrates, and molecular partners, together with the redun...
Source: Current Opinion in Neurobiology - March 8, 2019 Category: Neurology Authors: Lipinski M, Del Blanco B, Barco A Tags: Curr Opin Neurobiol Source Type: research

Continuing progress of spike sorting in the era of big data.
Abstract Engineering efforts are currently attempting to build devices capable of collecting neural activity from one million neurons in the brain. Part of this effort focuses on developing dense multiple-electrode arrays, which require post-processing via 'spike sorting' to extract neural spike trains from the raw signal. Gathering information at this scale will facilitate fascinating science, but these dreams are only realizable if the spike sorting procedure and data pipeline are computationally scalable, at or superior to hand processing, and scientifically reproducible. These challenges are all being amplifie...
Source: Current Opinion in Neurobiology - March 8, 2019 Category: Neurology Authors: Carlson D, Carin L Tags: Curr Opin Neurobiol Source Type: research

Backpropagation through time and the brain.
Abstract It has long been speculated that the backpropagation-of-error algorithm (backprop) may be a model of how the brain learns. Backpropagation-through-time (BPTT) is the canonical temporal-analogue to backprop used to assign credit in recurrent neural networks in machine learning, but there's even less conviction about whether BPTT has anything to do with the brain. Even in machine learning the use of BPTT in classic neural network architectures has proven insufficient for some challenging temporal credit assignment (TCA) problems that we know the brain is capable of solving. Nonetheless, recent work in machi...
Source: Current Opinion in Neurobiology - March 6, 2019 Category: Neurology Authors: Lillicrap TP, Santoro A Tags: Curr Opin Neurobiol Source Type: research

Coordination of neural patterning in the Drosophila visual system.
Abstract Precise formation of neuronal circuits requires the coordinated development of the different components of the circuit. Here, we review examples of coordination at multiples scales of development in one of the best-studied systems for neural patterning and circuit assembly, the Drosophila visual system, from coordination of gene expression in photoreceptors to the coordinated patterning of the different neuropiles of the optic lobe. PMID: 30849690 [PubMed - as supplied by publisher] (Source: Current Opinion in Neurobiology)
Source: Current Opinion in Neurobiology - March 5, 2019 Category: Neurology Authors: Courgeon M, Desplan C Tags: Curr Opin Neurobiol Source Type: research

TaDa! Analysing cell type-specific chromatin in vivo with Targeted DamID.
Abstract The emergence of neuronal diversity during development of the nervous system relies on dynamic changes in the epigenetic landscape of neural stem cells and their progeny. Targeted DamID (TaDa) is proving invaluable in identifying the genome-wide binding sites of chromatin-associated proteins in vivo, without fixation, cell isolation, or immunoprecipitation. The simplicity and efficiency of the technique have led to an ever-expanding TaDa toolbox. These tools enable profiling of gene expression and chromatin accessibility, as well as the identification of the genome-wide binding sites of chromatin complexe...
Source: Current Opinion in Neurobiology - March 4, 2019 Category: Neurology Authors: van den Ameele J, Krautz R, Brand AH Tags: Curr Opin Neurobiol Source Type: research

Neural populations for maintaining body fluid balance.
Abstract Fine balance between loss-of water and gain-of water is essential for maintaining body fluid homeostasis. The development of neural manipulation and mapping tools has opened up new avenues to dissect the neural circuits underlying body fluid regulation. Recent studies have identified several nodes in the brain that positively and negatively regulate thirst. The next step forward would be to elucidate how neural populations interact with each other to control drinking behavior. PMID: 30836260 [PubMed - as supplied by publisher] (Source: Current Opinion in Neurobiology)
Source: Current Opinion in Neurobiology - March 2, 2019 Category: Neurology Authors: Ichiki T, Augustine V, Oka Y Tags: Curr Opin Neurobiol Source Type: research

The development and assembly of the Drosophila adult ventral nerve cord.
Abstract In order to generate complex motor outputs, the nervous system integrates multiple sources of sensory information that ultimately controls motor neurons to generate coordinated movements. The neural circuits that integrate higher order commands from the brain and generate motor outputs are located in the nerve cord of the central nervous system. Recently, genetic access to distinct functional subtypes that make up the Drosophila adult ventral nerve cord has significantly begun to advance our understanding of the structural organization and functions of the neural circuits coordinating motor outputs. Moreo...
Source: Current Opinion in Neurobiology - February 28, 2019 Category: Neurology Authors: Venkatasubramanian L, Mann RS Tags: Curr Opin Neurobiol Source Type: research

Evolution of neuronal types and families.
Abstract Major questions in the evolution of neurons and nervous systems remain unsolved, such as the origin of the first neuron, the possible convergent evolution of neuronal phenotypes, and the transition from a relatively simple decentralized nerve net to the complex, centralized nervous systems found in modern bilaterian animals. In recent years, comparative single-cell transcriptomics has opened up new research avenues addressing these issues. Here, we review recent conceptual progress toward an evolutionary definition of cell types, and how it facilitates the identification and large-scale comparison of neur...
Source: Current Opinion in Neurobiology - February 28, 2019 Category: Neurology Authors: Arendt D, Bertucci PY, Achim K, Musser JM Tags: Curr Opin Neurobiol Source Type: research

Compartmentalized distributions of neuronal and glial cell-surface proteins pattern the synaptic network.
Wit J Abstract Neuronal identity and connectivity are closely linked. Single-cell sequencing studies show that different neuronal cell types express distinct combinations of cell-surface proteins important for synaptic connectivity and function. Emerging evidence indicates that glia-derived cell-surface proteins play critical roles in shaping connectivity as well. These studies begin to suggest that the proteins present on presynaptic and postsynaptic membranes, glial processes, and secreted into the synaptic cleft and extracellular matrix together confer unique surface identities to different types of synaptic co...
Source: Current Opinion in Neurobiology - February 28, 2019 Category: Neurology Authors: Apóstolo N, de Wit J Tags: Curr Opin Neurobiol Source Type: research

An integrative computational architecture for object-driven cortex.
Abstract Computational architecture for object-driven cortex Objects in motion activate multiple cortical regions in every lobe of the human brain. Do these regions represent a collection of independent systems, or is there an overarching functional architecture spanning all of object-driven cortex? Inspired by recent work in artificial intelligence (AI), machine learning, and cognitive science, we consider the hypothesis that these regions can be understood as a coherent network implementing an integrative computational system that unifies the functions needed to perceive, predict, reason about, and plan with phy...
Source: Current Opinion in Neurobiology - February 27, 2019 Category: Neurology Authors: Yildirim I, Wu J, Kanwisher N, Tenenbaum J Tags: Curr Opin Neurobiol Source Type: research

Subcellular control of membrane excitability in the axon.
Abstract Ion channels are microscopic pore proteins in the membrane that open and close in response to chemical and electrical stimuli. This simple concept underlies rapid electrical signaling in the brain as well as several important aspects of neural plasticity. Although the soma accounts for less than 1% of many neurons by membrane area, it has been the major site of measuring ion channel function. However, the axon is one of the longest processes found in cellular biology and hosts a multitude of critical signaling functions in the brain. Not only does the axon initiate and rapidly propagate action potentials ...
Source: Current Opinion in Neurobiology - February 19, 2019 Category: Neurology Authors: Alpizar SA, Cho IH, Hoppa MB Tags: Curr Opin Neurobiol Source Type: research

Analyzing biological and artificial neural networks: challenges with opportunities for synergy?
Abstract Deep neural networks (DNNs) transform stimuli across multiple processing stages to produce representations that can be used to solve complex tasks, such as object recognition in images. However, a full understanding of how they achieve this remains elusive. The complexity of biological neural networks substantially exceeds the complexity of DNNs, making it even more challenging to understand the representations they learn. Thus, both machine learning and computational neuroscience are faced with a shared challenge: how can we analyze their representations in order to understand how they solve complex task...
Source: Current Opinion in Neurobiology - February 19, 2019 Category: Neurology Authors: Barrett DG, Morcos AS, Macke JH Tags: Curr Opin Neurobiol Source Type: research

Septin functions during neuro-development, a yeast perspective.
Abstract Septins, discovered almost half a century ago in yeast, have prominent contributions in a broad range of morphological and functional processes from yeast to human. Septins now emerge as key players of neurodevelopment and more specifically of the mechanisms driving the complex morphological differentiation and compartmentalization of neurons that are fundamental to their function. We review here recent advances in Septin-mediated processes of neuron differentiation, which enlighten similarities and differences between neuron and yeast polarity programs. PMID: 30784977 [PubMed - as supplied by publis...
Source: Current Opinion in Neurobiology - February 18, 2019 Category: Neurology Authors: Falk J, Boubakar L, Castellani V Tags: Curr Opin Neurobiol Source Type: research

The travels of mRNAs in neurons: do they know where they are going?
Abstract Neurons are highly polarized cells that can extend processes far from the cell body. As such, transport of messenger RNAs serves as a set of blueprints for the synthesis of specific proteins at distal sites. RNA localization to dendrites and axons confers the ability to regulate translation with extraordinary precision in space and time. Although the rationale for RNA localization is quite compelling, it is unclear how a neuron orchestrates such a complex task of distributing over a thousand different mRNAs to their respective subcellular compartments. Recent single-molecule imaging studies have led to in...
Source: Current Opinion in Neurobiology - February 18, 2019 Category: Neurology Authors: Das S, Singer RH, Yoon YJ Tags: Curr Opin Neurobiol Source Type: research

Molecular constituents and localization of the ionotropic GABA receptor complex in vivo.
Abstract The ionotropic GABA receptor (GABAAR) mediates fast inhibition in the brain. The GABAAR pore-forming (α, β, and non-α/β) subunits were isolated approximately 30 years ago and have since been the focus of extensive studies. As a result, many properties of GABAARs, including subunit assembly and channel and pharmacological properties, have been discovered. However, several of the underlying mechanisms such as the process for the synaptic localization of GABAARs remain unsolved. A reinvestigation of native GABAAR complexes in the brain and primary neurons identified two major molecular ...
Source: Current Opinion in Neurobiology - February 18, 2019 Category: Neurology Authors: Tomita S Tags: Curr Opin Neurobiol Source Type: research

Surveillance and transportation of mitochondria in neurons.
Abstract Neurons need to allocate and sustain mitochondria to provide adequate energy and sufficient Ca2+-buffering capacity in each sub specialization of their extensive arborizations. Damaged mitochondria, which are highly deleterious to the neuron, must be rapidly repaired or eliminated, even when they are left at terminals extremely far away from the soma. The unique shape of neurons complicates the tasks of both transporting and clearing mitochondria. Errors in the underlying molecular regulations cause detrimental neurodegeneration. Here, we review the molecular machinery and regulatory mechanisms employed t...
Source: Current Opinion in Neurobiology - February 18, 2019 Category: Neurology Authors: Vanhauwaert R, Bharat V, Wang X Tags: Curr Opin Neurobiol Source Type: research

Vesicular degradation pathways in neurons: at the crossroads of autophagy and endo-lysosomal degradation.
Abstract Autophagy and endo-lysosomal degradation are two parallel degradation pathways essential for maintaining neuronal health and function. Autophagosomes and endosomes sequester cellular cargo through different mechanisms, but these pathways converge upon fusion with lysosomes. Both pathways are spatially regulated, with distinct features evident in the soma, axons, and dendrites, possibly as an adaptation to the unique morphology of neurons and the specific demands of each compartment. Relatively little is known about how autophagy and endo-lysosomal degradation interact and how their activities may be coord...
Source: Current Opinion in Neurobiology - February 18, 2019 Category: Neurology Authors: Boecker CA, Holzbaur EL Tags: Curr Opin Neurobiol Source Type: research

Normalization and pooling in hierarchical models of natural images.
Abstract Divisive normalization and subunit pooling are two canonical classes of computation that have become widely used in descriptive (what) models of visual cortical processing. Normative (why) models from natural image statistics can help constrain the form and parameters of such classes of models. We focus on recent advances in two particular directions, namely deriving richer forms of divisive normalization, and advances in learning pooling from image statistics. We discuss the incorporation of such components into hierarchical models. We consider both hierarchical unsupervised learning from image statistic...
Source: Current Opinion in Neurobiology - February 18, 2019 Category: Neurology Authors: Sanchez-Giraldo LG, Laskar MNU, Schwartz O Tags: Curr Opin Neurobiol Source Type: research

Pumping the brakes: suppression of synapse development by MDGA-neuroligin interactions.
Abstract Synapse development depends on a dynamic balance between synapse promoters and suppressors. MDGAs, immunoglobulin superfamily proteins, negatively regulate synapse development through blocking neuroligin-neurexin interactions. Recent analyses of MDGA-neuroligin complexes revealed the structural basis of this activity and indicate that MDGAs interact with all neuroligins with differential affinities. Surprisingly, analyses of mouse mutants revealed a functional divergence, with targeted mutation of Mdga1 and Mdga2 elevating inhibitory and excitatory synapses, respectively, on hippocampal pyramidal neurons....
Source: Current Opinion in Neurobiology - February 13, 2019 Category: Neurology Authors: Connor SA, Elegheert J, Xie Y, Craig AM Tags: Curr Opin Neurobiol Source Type: research

Mechanisms and regulation of dopamine release.
Abstract Dopamine controls motor functions, motivation, and reward-related learning through G-protein coupled receptor signaling. The current working model is that upon release, dopamine diffuses to influence many target cells via wide-spread receptors. Recent studies, however, suggest that dopamine release is fast and generates small signaling hotspots. In this review, we summarize progress on the understanding of the dopamine release apparatus and evaluate how its properties may shape dopamine signaling during firing. We discuss how mechanisms of regulation may act through this machinery and propose that striata...
Source: Current Opinion in Neurobiology - February 12, 2019 Category: Neurology Authors: Liu C, Kaeser PS Tags: Curr Opin Neurobiol Source Type: research

Non-coding RNAs: the gatekeepers of neural network activity.
Abstract Non-coding RNAs have emerged as potent regulators of numerous cellular processes. In neurons and circuits, these molecules serve especially critical functions that ensure neural activity is maintained within appropriate physiological parameters. Their targets include synaptic proteins, ion channels, neurotransmitter receptors, and components of essential signaling cascades. Here, we discuss how several species of non-coding RNAs (ncRNAs) regulate intrinsic excitability and synaptic transmission, both during development and in mature circuits. Furthermore, we present the relationships between aberrant ncRN...
Source: Current Opinion in Neurobiology - February 8, 2019 Category: Neurology Authors: Zampa F, Hartzell AL, Zolboot N, Lippi G Tags: Curr Opin Neurobiol Source Type: research

New insights on synaptic dysfunction in neuropsychiatric disorders.
ho AL Abstract Growing evidence implicates synaptic proteins in the pathogenesis of neuropsychiatric disorders such as autism spectrum disorder (ASD), intellectual disability (ID) and schizophrenia. In fact, mutations in genes encoding synaptic proteins are enriched and overlap among different conditions highlighting the complex and pleiotropic nature of these disorders. In this review, we discuss recently described candidate genes that affect excitatory synapse function and result in changes in spine number and morphology. Spine pathology has been observed in several animal models of disease and in human brain po...
Source: Current Opinion in Neurobiology - February 8, 2019 Category: Neurology Authors: Lima Caldeira G, Peça J, Carvalho AL Tags: Curr Opin Neurobiol Source Type: research

Statistical model-based approaches for functional connectivity analysis of neuroimaging data.
We present recent literature on model-based approaches to estimating functional connectivity from neuroimaging data. In contrast to the typical focus on a particular scientific question, we reframe a wider literature in terms of the underlying statistical model used. We distinguish between directed versus undirected and static versus time-varying connectivity. There are numerous advantages to a model-based approach, including easily specified inductive bias, handling limited data scenarios, and building complex models from simpler building blocks. PMID: 30739880 [PubMed - as supplied by publisher] (Source: Current Opi...
Source: Current Opinion in Neurobiology - February 7, 2019 Category: Neurology Authors: Foti NJ, Fox EB Tags: Curr Opin Neurobiol Source Type: research

Microtubule control of functional architecture in neurons.
Abstract Neurons are exquisitely polarized cells whose structure and function relies on microtubules. Microtubules in signal-receiving dendrites and signal-sending axons differ in their organization and microtubule-associated proteins. These differences, coupled with microtubule post-translational modifications, combine to locally regulate intracellular transport, morphology, and function. Recent discoveries provide new insight into the regulation of non-centrosomal microtubule arrays in neurons, the relationship between microtubule acetylation and mechanosensation, and the spatial patterning of microtubules that ...
Source: Current Opinion in Neurobiology - February 6, 2019 Category: Neurology Authors: Kelliher MT, Saunders HA, Wildonger J Tags: Curr Opin Neurobiol Source Type: research

Editorial overview: Neurobiology of learning and plasticity.
ml;m PJ PMID: 30712705 [PubMed - in process] (Source: Current Opinion in Neurobiology)
Source: Current Opinion in Neurobiology - February 1, 2019 Category: Neurology Authors: Waddell S, Sjöström PJ Tags: Curr Opin Neurobiol Source Type: research

Transcytosis at the blood-brain barrier.
Abstract The blood-brain barrier (BBB) is a functional interface separating the brain from the circulatory system and is essential for homeostasis of the central nervous system (CNS). The BBB regulates molecular flux to maintain an optimal environment for neuronal function and protects the brain from toxins and pathogens. Endothelial cells forming the walls of CNS blood vessels constitute the BBB. CNS endothelial cells exhibit two features that underlie the restrictive properties of the BBB: specialized tight junctions that prevent paracellular passage between the blood and the brain, and unusually low levels of v...
Source: Current Opinion in Neurobiology - January 29, 2019 Category: Neurology Authors: Ayloo S, Gu C Tags: Curr Opin Neurobiol Source Type: research

Neuronal cell types in the fly: single-cell anatomy meets single-cell genomics.
Abstract At around 150 000 neurons, the adult Drosophila melanogaster central nervous system is one of the largest species, for which a complete cellular catalogue is imminent. While numerically much simpler than mammalian brains, its complexity is still difficult to parse without grouping neurons into consistent types, which can number 1-1000 cells per hemisphere. We review how neuroanatomical and gene expression data are being used to discover neuronal types at scale. The correlation among multiple co-varying neuronal properties, including lineage, gene expression, morphology, connectivity, response prope...
Source: Current Opinion in Neurobiology - January 28, 2019 Category: Neurology Authors: Bates AS, Janssens J, Jefferis GS, Aerts S Tags: Curr Opin Neurobiol Source Type: research

Alternative splicing of neuronal genes: new mechanisms and new therapies.
Abstract Dynamic changes in alternative splicing during the life cycle of neurons support development and plasticity, and are implicated in disease pathology. Cell-specific alternative splicing programs coordinate exon selection across networks of functionally connected genes. In this opinion piece, we highlight recent publications that identify some of the molecular mechanisms-RNA and DNA binding proteins and epigenetic modifications-which direct cell-specific exon selection during pre-mRNA splicing. Aberrant splicing patterns are signature features of a growing number of diseases of the nervous system. Recent pu...
Source: Current Opinion in Neurobiology - January 28, 2019 Category: Neurology Authors: Lipscombe D, Lopez Soto EJ Tags: Curr Opin Neurobiol Source Type: research

Unc13: a multifunctional synaptic marvel.
Abstract Nervous systems are built on synaptic connections, and our understanding of these complex compartments has deepened over the past quarter century as the diverse fields of genetics, molecular biology, physiology, and biochemistry each made significant in-roads into synaptic function. On the presynaptic side, an evolutionarily conserved core fusion apparatus constructed from a handful of proteins has emerged, with Unc13 serving as a hub that coordinates nearly every aspect of synaptic transmission. This review briefly highlights recent studies on diverse aspects of Unc13 function including roles in SNARE as...
Source: Current Opinion in Neurobiology - January 25, 2019 Category: Neurology Authors: Dittman JS Tags: Curr Opin Neurobiol Source Type: research

Neuronal cell types in the annelid Platynereis dumerilii.
ely G Abstract The marine annelid Platynereis dumerilii is an invertebrate laboratory model for developmental biology and neuroscience. Its larval stages are small and transparent, enabling whole-body analyses of cell-type diversity and neuronal circuits. Here, we review the diversity of neuronal cell types in Platynereis. A variety of approaches have been used to identify cell types in Platynereis including whole-body gene expression atlases, single-cell RNA-seq and whole-body connectomics through serial EM reconstruction. The function of several cell types and neuronal circuits has also been analysed with experi...
Source: Current Opinion in Neurobiology - January 24, 2019 Category: Neurology Authors: Williams EA, Jékely G Tags: Curr Opin Neurobiol Source Type: research

Shared and derived features of cellular diversity in the human cerebral cortex.
Abstract The cerebral cortex is the hallmark of the mammalian nervous system, and its large size and cellular diversity in humans support our most sophisticated cognitive abilities. Although the basic cellular organization of the cortex is conserved across mammals, cells have diversified during evolution. An increasingly integrated taxonomy of cell types, especially with the advent of single-cell transcriptomic data, has revealed an unprecedented variety of human cortical cell subtypes. Here, we broadly review the cellular composition and diversity of the mammalian brain, and how progenitor pools generate cell sub...
Source: Current Opinion in Neurobiology - January 21, 2019 Category: Neurology Authors: Miller DJ, Bhaduri A, Sestan N, Kriegstein A Tags: Curr Opin Neurobiol Source Type: research

Bridging large-scale neuronal recordings and large-scale network models using dimensionality reduction.
Abstract A long-standing goal in neuroscience has been to bring together neuronal recordings and neural network modeling to understand brain function. Neuronal recordings can inform the development of network models, and network models can in turn provide predictions for subsequent experiments. Traditionally, neuronal recordings and network models have been related using single-neuron and pairwise spike train statistics. We review here recent studies that have begun to relate neuronal recordings and network models based on the multi-dimensional structure of neuronal population activity, as identified using dimensi...
Source: Current Opinion in Neurobiology - January 21, 2019 Category: Neurology Authors: Williamson RC, Doiron B, Smith MA, Yu BM Tags: Curr Opin Neurobiol Source Type: research

Neuronal and synaptic protein lifetimes.
Abstract Neuronal proteostasis is uniquely challenged by the extraordinary architecture of neurons, the vast number of synapses they form, and the need to precisely preserve function at individual synapses. Quantitative information on protein lifetimes can provide clues as to how these challenges are met. Advances in proteomics and mass spectrometry, which now enable comprehensive lifetime estimations for thousands of proteins, suggest that neuronal and synaptic protein lifetimes are unusually long, with half-lives typically ranging from days to weeks, even months and beyond for certain protein families. Half-live...
Source: Current Opinion in Neurobiology - January 21, 2019 Category: Neurology Authors: Cohen LD, Ziv NE Tags: Curr Opin Neurobiol Source Type: research

Neuronal identity control by terminal selectors in worms, flies, and chordates.
Abstract How do post-mitotic neurons acquire and maintain their terminal identity? Genetic mutant analysis in the nematode Caenorhabditis elegans has revealed common molecular programs that control neuronal identity. Neuron type-specific combinations of transcription factors, called terminal selectors, act as master regulatory factors to initiate and maintain terminal identity programs through direct regulation of neuron type-specific effector genes. We will provide here an update on recent studies that solidify the terminal selector concept in worms, flies and chordates. We will also describe how the terminal sel...
Source: Current Opinion in Neurobiology - January 18, 2019 Category: Neurology Authors: Hobert O, Kratsios P Tags: Curr Opin Neurobiol Source Type: research