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Volume 20 Issue 8, August 2017

In this issue, Chan et al. describe AAVs engineered for broad and efficient gene delivery to the central and peripheral nervous system through the vasculature. The cover shows dorsal root ganglion neurons expressing a mixture of three fluorescent proteins delivered via the new AAVs.10411172

News & Views

  • Effectiveness of EGFR treatment is impaired through an early adaptive response. TNF–JNK–Axl–ERK signaling contributes to this primary resistance to EGFR inhibition and might serve as novel target to improve EGFR inhibition.

    • Rolf Warta
    • Christel Herold-Mende
    News & Views


  • Loss of inhibition in a circuit in the primary somatosensory cortex that controls the activity of layer 5 neurons drives pain hypersensitivity. Restoring this inhibition resets the inhibitory–excitatory balance, producing analgesia.

    • Erika K Harding
    • Michael W Salter
    News & Views
  • A combination of computational modeling, neuroimaging and a causal manipulation of brain activity in humans reveals how the brain represents beliefs about how our choices will affect those of others we interact with.

    • Amit Etkin
    News & Views
  • A Cre-dependent capsid selection method, CREATE, was used to produce adeno-associated viral vectors that allow gene delivery to the entire central and peripheral nervous systems, with multicolor labeling of single cells.

    • Keisuke Yonehara
    • Botond Roska
    News & Views
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  • This study characterizes the properties of disease-causing mutations that produce sporadic amino acid replacements in proteins of people with autism and developmental delay. The mutations tend to cluster and reoccur at specific regions important to protein function, highlighting for future follow-up 200 candidate genes, many involved in neuronal signaling.

    • Madeleine R Geisheker
    • Gabriel Heymann
    • Evan E Eichler
  • The authors identified a protective genetic allele associated with lower PU.1 (SPI1) expression in myeloid cells by conducting a genome-wide scan of Alzheimer's disease (AD). PU.1 binds the promoters of AD-associated genes (e.g., CD33, MS4A4A & MS4A6A, TYROBP) and modulates their expression, suggesting it may reduce AD risk by regulating myeloid cell gene expression.

    • Kuan-lin Huang
    • Edoardo Marcora
    • Alison M Goate
  • Strong genetic evidence points to a significant role for heterozygous mutations to general chromatin remodeling factors, such as CHD8, in autism. Gompers et al. combine genomic, neuroanatomical and behavioral approaches to present an initial integrative picture of transcriptional mechanisms and widespread impacts of Chd8 haploinsufficiency across brain development in mice.

    • Andrea L Gompers
    • Linda Su-Feher
    • Alex S Nord
  • Noxious thermal and mechanical stimuli have to be faithfully detected and avoided to ensure survival. In this study, the authors uncover a modality-specific circuit responsible specifically for mechanonociceptive behavior in Drosophila. They show that the escape response to mechanical but not thermal noxious stimuli requires multisensory integration by mechanosensory neurons and neuromodulatory feedback signaling.

    • Chun Hu
    • Meike Petersen
    • Peter Soba
  • The precise mechanisms that cause human obesity remain unknown. Here the authors illustrate how increased expression of Cadm1, a mediator of synapse assembly, is relevant to weight gain. Reduction of Cadm1 in multiple brain regions promoted weight loss, and these observations provide insight into the neuronal pathways contributing to obesity.

    • Thomas Rathjen
    • Xin Yan
    • Matthew N Poy
  • Using two-color two-photon calcium imaging, the authors identified transformations of representations across synaptically connected pairs of neurons along a visual pathway to the Drosophila central complex. Neural responses to stimuli in the ipsilateral field are modulated by stimuli in the contralateral field, an effect that depends on past stimulus history.

    • Yi Sun
    • Aljoscha Nern
    • Vivek Jayaraman
  • Combining electrophysiology and computational modeling, the authors show that the dendrites of entorhinal cortex stellate and pyramidal cells are electrically excitable and that this improves the robustness of grid cell firing. The results suggest that active dendrites are critical for spatial navigation, a fundamental computation in the brain.

    • Christoph Schmidt-Hieber
    • Gabija Toleikyte
    • Michael Häusser
  • Using in vivo calcium imaging in a mouse model of neuropathic pain, the authors found a persistent increase in the activity of somatosensory cortex pyramidal neurons following peripheral nerve injury. Repeated pharmacogenetic activation of somatostatin-expressing inhibitory neurons after injury not only corrected this abnormal cortical activity but also prevented the development of chronic pain.

    • Joseph Cichon
    • Thomas J J Blanck
    • Guang Yang
  • Corticospinal cells of the motor cortex act as a direct link between the cortex and movement-generating circuits within the spinal cord. The authors demonstrate that the relationship between activity of these cells and movement changes with time and learning, indicating a flexible cortical output to drive movements.

    • Andrew J Peters
    • Jun Lee
    • Takaki Komiyama
  • The authors show that transcranial magnetic disruption of the right temporoparietal junction decreases strategic behavior during competitive interactions. The altered behavior relates to neural activity changes both locally and in interconnected prefrontal areas. These brain networks may causally underlie the ability to predict the behavior of other agents.

    • Christopher A Hill
    • Shinsuke Suzuki
    • Christian C Ruff
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Technical Report

  • The authors report two new engineered AAV capsids that efficiently deliver genes throughout the adult central and peripheral nervous systems after intravenous administration. Complementing these capsids is an AAV toolbox that enables cell morphology and genetic manipulation studies of defined neural cell types in transgenic or wild-type animals.

    • Ken Y Chan
    • Min J Jang
    • Viviana Gradinaru
    Technical Report
  • The authors demonstrate that optical fibers with tapered tips can homogenously illuminate either elongated brain structures or dynamically selected subregions. Tapered fibers achieve efficient optogenetic stimulation in vivo with minimal tissue damage. In addition, a single fiber can deliver light of multiple wavelengths to independently controlled regions.

    • Ferruccio Pisanello
    • Gil Mandelbaum
    • Bernardo L Sabatini
    Technical Report
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