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Current Opinion in Neurobiology

Gladys Lima Caldeira, João Peça, Ana Luísa Carvalho
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...
February 8, 2019: Current Opinion in Neurobiology
Federico Zampa, Andrea L Hartzell, Norjin Zolboot, Giordano Lippi
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...
February 8, 2019: Current Opinion in Neurobiology
Nicholas J Foti, Emily B Fox
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...
February 7, 2019: Current Opinion in Neurobiology
Michael T Kelliher, Harriet Aj Saunders, Jill Wildonger
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 regulates motor activity and cargo delivery in axons and dendrites...
February 6, 2019: Current Opinion in Neurobiology
Swathi Ayloo, Chenghua Gu
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 vesicle trafficking that limit transcellular transport or transcytosis...
January 29, 2019: Current Opinion in Neurobiology
Diane Lipscombe, Eduardo Javier Lopez Soto
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...
January 28, 2019: Current Opinion in Neurobiology
Alexander Shakeel Bates, Jasper Janssens, Gregory Sxe Jefferis, Stein Aerts
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 properties and shared behavioral significance is essential to the definition of neuronal cell type...
January 28, 2019: Current Opinion in Neurobiology
Jeremy S Dittman
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 assembly and quality control, release site building, calcium channel proximity, and short-term synaptic plasticity...
January 25, 2019: Current Opinion in Neurobiology
Elizabeth A Williams, Gáspár Jékely
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...
January 24, 2019: Current Opinion in Neurobiology
Laurie D Cohen, Noam E Ziv
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...
January 21, 2019: Current Opinion in Neurobiology
Ryan C Williamson, Brent Doiron, Matthew A Smith, Byron M Yu
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 dimensionality reduction...
January 21, 2019: Current Opinion in Neurobiology
Daniel J Miller, Aparna Bhaduri, Nenad Sestan, Arnold Kriegstein
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 subtypes during development...
January 21, 2019: Current Opinion in Neurobiology
Oliver Hobert, Paschalis Kratsios
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...
January 18, 2019: Current Opinion in Neurobiology
Andrew C Halley, Leah Krubitzer
A central question in comparative neurobiology concerns how evolution has produced brains with expanded neocortices, composed of more areas with unique connectivity and functional properties. Some mammalian lineages, such as primates, exhibit exceptionally large cortices relative to the amount of sensory inputs from the dorsal thalamus, and this expansion is associated with a larger number of distinct cortical areas, composing a larger proportion of the cortical sheet. We propose a link between the organization of the neocortex and its expansion relative to the size of the dorsal thalamus, based on a combination of work in comparative neuroanatomy and experimental research...
January 15, 2019: Current Opinion in Neurobiology
Fabian Rentzsch, Celina Juliano, Brigitte Galliot
Cnidarians shared a common ancestor with bilaterians more than 600 million years ago. This sister group relationship gives them an informative phylogenetic position for understanding the fascinating morphological and molecular cell type diversity of bilaterian nervous systems. Moreover, cnidarians display novel features such as endodermal neurogenesis and independently evolved centralizations, which provide a platform for understanding the evolution of nervous system innovations. In recent years, the application of modern genomic tools has significantly advanced our understanding of cnidarian nervous system structure and function...
January 14, 2019: Current Opinion in Neurobiology
Eli J Cornblath, David M Lydon-Staley, Danielle S Bassett
The development of next-generation therapies for neuropsychiatric illness will likely rely on a precise and accurate understanding of human brain dynamics. Toward this end, researchers have focused on collecting large quantities of neuroimaging data. For simplicity, we will refer to large cross-sectional neuroimaging studies as broad studies and to intensive longitudinal studies as deep studies. Recent progress in identifying illness subtypes and predicting treatment response in neuropsychiatry has been supported by these study designs, along with methods bridging machine learning and network science...
January 11, 2019: Current Opinion in Neurobiology
Megan Crow, Jesse Gillis
Recent technical advances have enabled transcriptomics experiments at an unprecedented scale, and single-cell profiles from neural tissue are accumulating rapidly. There has been considerable effort to use these profiles to understand cell diversity, primarily through unsupervised clustering and differential expression analysis. However, current practices to validate these findings vary. In this review, we describe recent efforts to evaluate clusters from single-cell RNA-sequencing data, and provide a framework for considering current evidence and practices in terms of their capacity to establish principles of cell biology...
January 6, 2019: Current Opinion in Neurobiology
Zhe Feng, Xudong Chen, Menglong Zeng, Mingjie Zhang
The postsynaptic density (PSD) is an electron dense, semi-membrane bound compartment that lies beneath postsynaptic membranes. This region is densely packed with thousands of proteins that are involved in extensive interactions. During synaptic plasticity, the PSD undergoes changes in size and composition along with changes in synaptic strength that lead to long term potentiation (LTP) or depression (LTD). It is therefore essential to understand the organization principles underlying PSD assembly and rearrangement...
December 29, 2018: Current Opinion in Neurobiology
Eftychios A Pnevmatikakis
Calcium imaging is a popular tool among neuroscientists because of its capability to monitor in vivo large neural populations across weeks with single neuron and single spike resolution. Before any downstream analysis, the data needs to be pre-processed to extract the location and activity of the neurons and processes in the observed field of view. The ever increasing size of calcium imaging datasets necessitates scalable analysis pipelines that are reproducible and fully automated. This review focuses on recent methods for addressing the pre-processing problems that arise in calcium imaging data analysis, and available software tools for high throughput analysis pipelines...
December 15, 2018: Current Opinion in Neurobiology
Carsen Stringer, Marius Pachitariu
Electrophysiology has long been the workhorse of neuroscience, allowing scientists to record with millisecond precision the action potentials generated by neurons in vivo. Recently, calcium imaging of fluorescent indicators has emerged as a powerful alternative. This technique has its own strengths and weaknesses and unique data processing problems and interpretation confounds. Here we review the computational methods that convert raw calcium movies to estimates of single neuron spike times with minimal human supervision...
December 7, 2018: Current Opinion in Neurobiology
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