Reviews & Analysis

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  • The neocortex and the thalamus are connected by looping circuits, enabling cortical function. In this Review, Gordon Shepherd and Naoki Yamawaki examine the patterns of connectivity between the major types of cortical and thalamic neurons and how these cortico-thalamo-cortical loops relate to corticocortical circuits.

    • Gordon M. G. Shepherd
    • Naoki Yamawaki
    Review Article
  • Evidence suggests that socio-economic status can affect not only the outcome of structural and functional development of the brain but also its rate. Tooley, Bassett and Mackey review this evidence and suggest that the valence and frequency of early experiences interact to influence brain development.

    • Ursula A. Tooley
    • Danielle S. Bassett
    • Allyson P. Mackey
  • Neuroscience can explain cognition by considering single neurons and their connections (a ‘Sherringtonian’ view) or by considering neural spaces constructed by populations of neurons (a ‘Hopfieldian’ view). In this Perspective, Barack and Krakauer argue that the Hopfieldian view has the conceptual resources to explain cognition more fully the Sherringtonian view.

    • David L. Barack
    • John W. Krakauer
  • The impairment of brain fluid homeostasis is a feature of various conditions, highlighting the need to better understand brain water transport for drug development. Here, Nanna MacAulay reviews the molecular mechanisms underlying transmembrane water movement in neurons and glia and across brain barriers, emphasizing the part played by water cotransporters in this process.

    • Nanna MacAulay
    Review Article
  • Dopamine is often portrayed as a diffuse, slow neuromodulator, yet such signalling cannot explain its broad and sometimes rapid roles. Here, Liu, Goel and Kaeser review recent insights into dopamine release and receptors and present a new framework — the domain-overlap model — for dopamine signalling.

    • Changliang Liu
    • Pragya Goel
    • Pascal S. Kaeser
    Review Article
  • Ion channel dysfunctions contribute significantly to fragile X pathophysiology. In this Review, Deng and Klyachko discuss the mechanisms underlying the effects of these channelopathies in fragile X syndrome, and the therapeutic potential of pharmacological interventions that target ion channels.

    • Pan-Yue Deng
    • Vitaly A. Klyachko
    Review Article
  • In this Perspective, Koban, Gianaros, Kober and Wager describe neural systems that construct models of the ‘self-in-context’. Such models endow events with personal meaning and enable predictive control over behaviour and peripheral physiology — with implications for health and disease.

    • Leonie Koban
    • Peter J. Gianaros
    • Tor D. Wager
  • Different voltage-gated sodium channels contribute to the transmission of painful information. In this Review, Goodwin and McMahon ask which channels are involved in nociceptor transduction, transmission and transmitter release and why individuals with Nav1.7 null mutations have a painless phenotype.

    • George Goodwin
    • Stephen B. McMahon
    Review Article
  • Dysfunctional GABAergic signalling is common to various neurodevelopmental disorders (NDDs). Tang, Jaenisch and Sur give an overview of the contribution of GABA signalling dysfunction to NDD aetiology and examine how mechanistic insights into such disruption can be used to advance treatments for NDDs.

    • Xin Tang
    • Rudolf Jaenisch
    • Mriganka Sur
    Review Article
  • The development of advanced imaging methods such as super-resolution microscopy and tissue imaging has revolutionized our approach to explore the brain. In this Review, Choquet and colleagues review how the latest molecular tools are combined with imaging techniques to investigate neural function at a greater resolution than previously possible.

    • Daniel Choquet
    • Matthieu Sainlos
    • Jean-Baptiste Sibarita
    Review Article
  • Accumulation of TAR DNA-binding protein 43 (TDP43) in the neuronal cytoplasm and its loss from the nucleus are characteristic features of several neurodegenerative diseases. Tziortzouda, Van Den Bosch and Hirth describe three intrinsic mechanisms that control TDP43 levels and localization and are altered to drive pathology.

    • Paraskevi Tziortzouda
    • Ludo Van Den Bosch
    • Frank Hirth
    Review Article
  • In this Review, Denoth-Lippuner and Jessberger present recent insights into adult hippocampal neurogenesis in rodents — from stem cell activation to the integration of newborn neurons into pre-existing circuits — and describe how newborn neurons affect brain function.

    • Annina Denoth-Lippuner
    • Sebastian Jessberger
    Review Article
  • Inactivation of the gene encoding fragile X mental retardation protein (FMRP) drives the impairments in brain development and function that underlie fragile X syndrome. Richter and Zhao illustrate how innovative genetic and molecular biology tools have enhanced our understanding of both FMRP’s function and the causes of fragile X syndrome pathophysiology.

    • Joel D. Richter
    • Xinyu Zhao
    Review Article
  • Flexibility is critical for the optimal adaptation of thoughts and actions under changing circumstances. In this Review, Uddin summarizes research that has identified cognitive processes and neural systems supporting flexibility and discusses ways to improve flexibility across the lifespan.

    • Lucina Q. Uddin
    Review Article
  • A substantial burden of neurological disease is related to mutations in three sodium channel genes: SCN1A, SCN2A and SCN8A. In this Review, Meisler and colleagues discuss the neurological disorders associated with these mutations and also the therapeutic opportunities that are being investigated as a result of these recent mechanistic insights.

    • Miriam H. Meisler
    • Sophie F. Hill
    • Wenxi Yu
    Review Article
  • The role of the default mode network (DMN) is unclear. In this Perspective, Yeshurun, Nguyen and Hasson review evidence that the DMN integrates extrinsic inputs with intrinsic information over long timescales, enabling it to represent meaning in a way that can be shared between individuals.

    • Yaara Yeshurun
    • Mai Nguyen
    • Uri Hasson
  • Lewy bodies, which are α-synuclein-rich intracellular inclusions, are pathological hallmarks of several neurodegenerative diseases, notably Parkinson disease. In this Review, Fares, Jagannath and Lashuel examine the biochemical, structural and morphological features of Lewy bodies as well as how α-synuclein pathology may form and spread.

    • Mohamed Bilal Fares
    • Somanath Jagannath
    • Hilal A. Lashuel
    Review Article
  • The molecular basis of trans-synaptic signalling by Neurexins plays an important role in synapse organization. In this Review, Scheiffele and colleagues link cell type-specific alternative splicing to the combinatorial action of Neurexin isoforms, and provide a mechanistic framework for Neurexin functions in synapse organization.

    • Andrea M. Gomez
    • Lisa Traunmüller
    • Peter Scheiffele
    Review Article
  • Local mRNA translation is essential for the function of polarized cells, such as neurons. Twiss and colleagues provide an overview of the cellular mechanisms that coordinate the transport and translation of axonal mRNAs, allowing the axon to respond to changing physiological demands.

    • Irene Dalla Costa
    • Courtney N. Buchanan
    • Jeffery L. Twiss
    Review Article
  • The formation of the nodes of Ranvier in myelinated axons involves a specific clustering of ion channels. In this Review, Rasband and Peles describe two independent, glia-directed mechanisms that converge on the axonal cytoskeleton to cluster and maintain nodal ion channels.

    • Matthew N. Rasband
    • Elior Peles
    Review Article