Nature Neuroscience Contents: August 2017 Volume 20 Number 8, pp 1035 - 1189

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Advertisement An interdisciplinary journal dedicated to publishing high-quality open research relevant to all aspects of schizophrenia and psychosis. Explore the benefits of submitting your next research article. TABLE OF CONTENTS August 2017 Volume 20, Issue 8 News and Views Articles Resources Technical Reports Corrigenda Erratum Advertisement   Stay informed with the best science news from Nature and beyond. Curated by our global news team and delivered direct to your inbox every weekday, free of charge.  Click to learn more Subscribe   Facebook   RSS   Recommend to library   Twitter   News and Views Top Helping EGFR inhibition to block cancer   pp1035 - 1037 Rolf Warta and Christel Herold-Mende doi:10.1038/nn.4605 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. See also: Article by Guo et al. VIP cortical conductors set the tone for chronic pain   pp1037 - 1038 Erika K Harding and Michael W Salter doi:10.1038/nn.4609 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. See also: Article by Cichon et al. Is the boss watching?   pp1039 - 1040 Amit Etkin doi:10.1038/nn.4603 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. See also: Article by Hill et al. CREATEd viruses go global   pp1041 - 1042 Keisuke Yonehara and Botond Roska doi:10.1038/nn.4600 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. See also: Technical Report by Chan et al. Neuroscience JOBS of the week Postdoctoral Research Fellow in Systems Neuroscience University of Sussex Research Fellow: Neuroscience of Pain, Analgesics, AAV Gene Therapy Job Mayo Clinic Assistant Professor, Behavioral Neuroscience Western Washington University Postdoctoral position in Neuroscience: neural networks underlying behavior Max Planck Society, caesar Post-doctoral Fellow / Staff Scientist in Developmental Neuroscience Children's National Health Systems More Science jobs from Neuroscience EVENT 3rd Annual Neuroscience R&D Technologies Conference 28.09.17 London, UK More science events from Articles Top Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains   pp1043 - 1051 Madeleine R Geisheker, Gabriel Heymann, Tianyun Wang, Bradley P Coe, Tychele N Turner et al. doi:10.1038/nn.4589 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 [sim]200 candidate genes, many involved in neuronal signaling. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease   pp1052 - 1061 Kuan-lin Huang, Edoardo Marcora, Anna A Pimenova, Antonio F Di Narzo, Manav Kapoor et al. doi:10.1038/nn.4587 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. Germline Chd8 haploinsufficiency alters brain development in mouse   pp1062 - 1073 Andrea L Gompers, Linda Su-Feher, Jacob Ellegood, Nycole A Copping, M Asrafuzzaman Riyadh et al. doi:10.1038/nn.4592 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. A TNF-JNK-Axl-ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma   pp1074 - 1084 Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani et al. doi:10.1038/nn.4584 Aberrant EGFR signaling is common in glioblastoma. The authors show that inhibiting EGFR leads to increased secretion of TNF and activation of a survival pathway in cancer cells. A combined inhibition of EGFR and TNF signaling inhibits tumor growth in a mouse model, suggesting a new treatment for patients with glioblastoma. See also: News and Views by Warta & Herold-Mende Sensory integration and neuromodulatory feedback facilitate Drosophila mechanonociceptive behavior   pp1085 - 1095 Chun Hu, Meike Petersen, Nina Hoyer, Bettina Spitzweck, Federico Tenedini et al. doi:10.1038/nn.4580 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. Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1   pp1096 - 1103 Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song et al. doi:10.1038/nn.4590 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. Neural signatures of dynamic stimulus selection in Drosophila   pp1104 - 1113 Yi Sun, Aljoscha Nern, Romain Franconville, Hod Dana, Eric R Schreiter et al. doi:10.1038/nn.4581 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. Active dendritic integration as a mechanism for robust and precise grid cell firing   pp1114 - 1121 Christoph Schmidt-Hieber, Gabija Toleikyte, Laurence Aitchison, Arnd Roth, Beverley A Clark et al. doi:10.1038/nn.4582 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. Activation of cortical somatostatin interneurons prevents the development of neuropathic pain   pp1122 - 1132 Joseph Cichon, Thomas J J Blanck, Wen-Biao Gan and Guang Yang doi:10.1038/nn.4595 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. See also: News and Views by Harding & Salter Reorganization of corticospinal output during motor learning   pp1133 - 1141 Andrew J Peters, Jun Lee, Nathan G Hedrick, Keelin O'Neil and Takaki Komiyama doi:10.1038/nn.4596 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. A causal account of the brain network computations underlying strategic social behavior   pp1142 - 1149 Christopher A Hill, Shinsuke Suzuki, Rafael Polania, Marius Moisa, John P O'Doherty et al. doi:10.1038/nn.4602 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. See also: News and Views by Etkin Resources Top Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders   pp1150 - 1161 Jing Li, Wangshu Zhang, Hui Yang, Daniel P Howrigan, Brent Wilkinson et al. doi:10.1038/nn.4594 Using large-scale analysis of protein interactions and bioinformatics, Li et al. describe the organization of the core-scaffold machinery of the postsynaptic density and its assembly in protein-interaction networks. The authors show how mutations associated with complex brain disorders are distributed along spatiotemporal protein complexes and modulate their protein interactions. Transcriptomic analysis of purified human cortical microglia reveals age-associated changes   pp1162 - 1171 Thais F Galatro, Inge R Holtman, Antonio M Lerario, Ilia D Vainchtein, Nieske Brouwer et al. doi:10.1038/nn.4597 Microglia are the macrophages of the CNS, with innate neuroimmune function, and play important roles in tissue homeostasis, CNS development and neurodegeneration. Here human microglial gene expression profiles were generated. Human and mouse microglia were highly similar, except for aging-regulated genes, indicating that microglial aging differs between humans and mice. Technical Reports Top Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems   pp1172 - 1179 Ken Y Chan, Min J Jang, Bryan B Yoo, Alon Greenbaum, Namita Ravi et al. doi:10.1038/nn.4593 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. See also: News and Views by Yonehara & Roska Dynamic illumination of spatially restricted or large brain volumes via a single tapered optical fiber   pp1180 - 1188 Ferruccio Pisanello, Gil Mandelbaum, Marco Pisanello, Ian A Oldenburg, Leonardo Sileo et al. doi:10.1038/nn.4591 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. Corrigenda Top Corrigendum: Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles   p1189 Anusha Mishra, James P Reynolds, Yang Chen, Alexander V Gourine, Dmitri A Rusakov et al. doi:10.1038/nn0817-1189a Corrigendum: A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH   p1189 Henning Fenselau, John N Campbell, Anne M J Verstegen, Joseph C Madara, Jie Xu et al. doi:10.1038/nn0817-1189b Corrigendum: Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior   p1189 Nicholas J Edwards, Hugo A Tejeda, Marco Pignatelli, Shiliang Zhang, Ross A McDevitt et al. doi:10.1038/nn0817-1189c Corrigendum: Dopamine transients are sufficient and necessary for acquisition of model-based associations   p1189 Melissa J Sharpe, Chun Yun Chang, Melissa A Liu, Hannah M Batchelor, Lauren E Mueller et al. doi:10.1038/nn0817-1189e Erratum Top Erratum: Persistently active neurons in human medial frontal and medial temporal lobe support working memory   p1189 Jan Kaminski, Shannon Sullivan, Jeffrey M Chung, Ian B Ross, Adam N Mamelak et al. doi:10.1038/nn0817-1189d Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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