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  • The translation of analgesic drug candidates to the clinic relies upon successful preclinical pain modelling. In this Review, Stucky and colleagues describe recent trends in the methods used to model pain in laboratory animals and provide recommendations for experimental designs that may increase translational success.

    • Katelyn E. Sadler
    • Jeffrey S. Mogil
    • Cheryl L. Stucky
    Review Article
  • The amyloid hypothesis has been the dominant model for the pathogenesis of Alzheimer disease for several decades. In this Perspective, Giovanni Frisoni and colleagues examine evidence for and against this hypothesis before outlining an alternative model, the probabilistic model of Alzheimer disease.

    • Giovanni B. Frisoni
    • Daniele Altomare
    • Bruno Dubois
    Perspective
  • Numerous energy-demanding cellular processes contribute to synaptic activity and function. Li and Sheng describe the mechanisms that regulate presynaptic energy supply to ensure that neurons can meet these demands and maintain their functions during periods of intensive synaptic activity.

    • Sunan Li
    • Zu-Hang Sheng
    Review Article
  • In their flagship paper, the BRAIN Initiative Cell Census Network (BICCN) describes the classification and analysis of cell types in the mammalian primary motor cortex.

    • Katherine Whalley
    Research Highlight
  • Environmental stressors, including extreme ambient temperature, the presence of pathogens or predators, and a lack of food, can profoundly influence animal behaviour. In this Perspective, Nakamura, Nakamura and Kataoka present a hypothalamomedullary network model for physiological responses to various environmental stressors.

    • Kazuhiro Nakamura
    • Yoshiko Nakamura
    • Naoya Kataoka
    Perspective
  • Synaptic dysfunction is a key feature of Alzheimer disease. In this Review, Padmanabhan, Kneynsberg and Götz examine insights provided by super-resolution microscopy into synaptic architecture and organization in Alzheimer disease, focusing on amyloid-β and tau, thought to be two key players in the pathophysiology of the disease.

    • Pranesh Padmanabhan
    • Andrew Kneynsberg
    • Jürgen Götz
    Review Article
  • Targeting two neuronal populations simultaneously with brief bursts of deep brain stimulation (DBS) induces longer-lasting beneficial effects on motor function than conventional DBS in dopamine-depleted mice.

    • Darran Yates
    Research Highlight
  • Hands enable us to interact with objects in precise and versatile ways. In this Review, Sobinov and Bensmaia discuss aspects of mundane and expert manual behaviours, the anatomical complexity of the human hand and neural mechanisms that underlie manual dexterity.

    • Anton R. Sobinov
    • Sliman J. Bensmaia
    Review Article
  • Gastrin-releasing peptide (GRP) signalling regulates vasoactive-intestinal peptide (VIP)-expressing cortical cells in a disinhibitory microcircuit that modulates a cortex-dependent behaviour.

    • Jake Rogers
    Research Highlight
  • In a mouse model of mesial temporal lobe epilepsy, reactive hippocampal glia were reprogrammed into functional GABAergic interneurons that integrated into local circuits and reduced seizure incidence.

    • Sian Lewis
    Research Highlight
  • Fibroblasts in the CNS have been assigned a role in fibrotic scar formation in response to injury and inflammation but might perform additional roles attributed to other cell types. In this Review, Dorrier and colleagues discuss the available evidence regarding fibroblast functions in the CNS.

    • Cayce E. Dorrier
    • Hannah E. Jones
    • Richard Daneman
    Review Article
  • Two studies probe the mechanisms of gene expression regulation that have contributed to human-specific features of the prefrontal cortex.

    • Katherine Whalley
    Research Highlight
  • The encoding of itch by peripheral and central neural circuits is a topic of long-standing interest in the somatosensory field. Here, Zhou-Feng Chen outlines a model for itch coding that emphasizes the role of neuropeptides in conveying itch information from the periphery to the spinal cord.

    • Zhou-Feng Chen
    Perspective
  • The sympathetic regulation of bodily functions relies on precise connections between sympathetic neurons and peripheral organs. In this Review, Scott-Solomon and colleagues discuss the mechanisms underlying the development of the sympathetic nervous system and provide insight into disorders regulated by this branch of the nervous system.

    • Emily Scott-Solomon
    • Erica Boehm
    • Rejji Kuruvilla
    Review Article
  • A new study describes opposing cell-specific RhoA-dependent mechanisms linking the intrinsic regulation of neuronal microtubule dynamics and the extrinsic regulation of reactive astrocyte signalling that restrain axon regeneration.

    • Jake Rogers
    Research Highlight
  • The raphe nucleus contains specific populations of serotonergic neurons that express either orexin type 1 or type 2 receptors that directionally regulate plasma glucose and peripheral energy metabolism.

    • Sian Lewis
    Research Highlight
  • Clathrin undergoes axonal transport as stable ‘packets’, which become more dynamic at synapses.

    • Darran Yates
    Research Highlight
  • Male-only studies predominate preclinical research on anxiety and depression. In this Review, Bangasser and Cuarenta discuss how, since the inclusion of female subjects, new mechanisms have been identified that underlie vulnerability to these disorders, and that reveal novel targets for treatments.

    • Debra A. Bangasser
    • Amelia Cuarenta
    Review Article
  • Neural circuits in the mammalian central nervous system are modified in response to neural activity during development. In this Review, Faust and colleagues provide an overview of the mechanisms underlying developmental synaptic pruning and how alterations in this process can occur in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia.

    • Travis E. Faust
    • Georgia Gunner
    • Dorothy P. Schafer
    Review Article
  • Developing a better understanding of neural codes should enable the links between stimuli, brain activity and behaviour to become clearer. In this Perspective, Kriegeskorte and Wei examine neural tuning and representational geometry — complementary approaches used to understand neural codes — and the relationship between them.

    • Nikolaus Kriegeskorte
    • Xue-Xin Wei
    Perspective