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

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August 2017 Volume 20, Issue 8

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Helping EGFR inhibition to block cancer   pp1035 - 1037
Rolf Warta and Christel Herold-Mende
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
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
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
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.

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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.
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.
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.
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.
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.
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.
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.
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.
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
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
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.
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



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.
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.
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


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.
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.
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.



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.

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.

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.

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.



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.

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