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Nature Neuroscience

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https://www.readbyqxmd.com/read/28805816/selective-attention-within-the-foveola
#1
Martina Poletti, Michele Rucci, Marisa Carrasco
Efficient control of attentional resources and high-acuity vision are both fundamental for survival. Shifts in visual attention are known to covertly enhance processing at locations away from the center of gaze, where visual resolution is low. It is unknown, however, whether selective spatial attention operates where the observer is already looking-that is, within the high-acuity foveola, the small yet disproportionally important rod-free region of the retina. Using new methods for precisely controlling retinal stimulation, here we show that covert attention flexibly improves and speeds up both detection and discrimination at loci only a fraction of a degree apart within the foveola...
August 14, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28805815/aav-mediated-direct-in-vivo-crispr-screen-identifies-functional-suppressors-in-glioblastoma
#2
Ryan D Chow, Christopher D Guzman, Guangchuan Wang, Florian Schmidt, Mark W Youngblood, Lupeng Ye, Youssef Errami, Matthew B Dong, Michael A Martinez, Sensen Zhang, Paul Renauer, Kaya Bilguvar, Murat Gunel, Phillip A Sharp, Feng Zhang, Randall J Platt, Sidi Chen
A causative understanding of genetic factors that regulate glioblastoma pathogenesis is of central importance. Here we developed an adeno-associated virus-mediated, autochthonous genetic CRISPR screen in glioblastoma. Stereotaxic delivery of a virus library targeting genes commonly mutated in human cancers into the brains of conditional-Cas9 mice resulted in tumors that recapitulate human glioblastoma. Capture sequencing revealed diverse mutational profiles across tumors. The mutation frequencies in mice correlated with those in two independent patient cohorts...
August 14, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28805814/cerebellar-granule-cell-replenishment-postinjury-by-adaptive-reprogramming-of-nestin-progenitors
#3
Alexandre Wojcinski, Andrew K Lawton, N Sumru Bayin, Zhimin Lao, Daniel N Stephen, Alexandra L Joyner
Regeneration of several organs involves adaptive reprogramming of progenitors, but the intrinsic capacity of the developing brain to replenish lost cells remains largely unknown. Here we found that the developing cerebellum has unappreciated progenitor plasticity, since it undergoes near full growth and functional recovery following acute depletion of granule cells, the most plentiful neuron population in the brain. We demonstrate that following postnatal ablation of granule cell progenitors, Nestin-expressing progenitors, specified during mid-embryogenesis to produce astroglia and interneurons, switch their fate and generate granule neurons in mice...
August 14, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28805813/analysis-of-genome-wide-association-data-highlights-candidates-for-drug-repositioning-in-psychiatry
#4
Hon-Cheong So, Carlos Kwan-Long Chau, Wan-To Chiu, Kin-Sang Ho, Cho-Pong Lo, Stephanie Ho-Yue Yim, Pak-Chung Sham
Knowledge of psychiatric disease genetics has advanced rapidly during the past decade with the advent of genome-wide association studies (GWAS). However, less progress has been made in harnessing these data to reveal new therapies. Here we propose a framework for drug repositioning by comparing transcriptomes imputed from GWAS data with drug-induced gene expression profiles from the Connectivity Map database and apply this approach to seven psychiatric disorders. We found a number of repositioning candidates, many supported by preclinical or clinical evidence...
August 14, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28783140/structure-in-neural-population-recordings-an-expected-byproduct-of-simpler-phenomena
#5
Gamaleldin F Elsayed, John P Cunningham
Neuroscientists increasingly analyze the joint activity of multineuron recordings to identify population-level structures believed to be significant and scientifically novel. Claims of significant population structure support hypotheses in many brain areas. However, these claims require first investigating the possibility that the population structure in question is an expected byproduct of simpler features known to exist in data. Classically, this critical examination can be either intuited or addressed with conventional controls...
August 7, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28783139/antipsychotic-induced-hdac2-transcription-via-nf-%C3%AE%C2%BAb-leads-to-synaptic-and-cognitive-side-effects
#6
Daisuke Ibi, Mario de la Fuente Revenga, Nebojsa Kezunovic, Carolina Muguruza, Justin M Saunders, Supriya A Gaitonde, José L Moreno, Maryum K Ijaz, Vishaka Santosh, Alexey Kozlenkov, Terrell Holloway, Jeremy Seto, Aintzane García-Bea, Mitsumasa Kurita, Grace E Mosley, Yan Jiang, Daniel J Christoffel, Luis F Callado, Scott J Russo, Stella Dracheva, Juan F López-Giménez, Yongchao Ge, Carlos R Escalante, J Javier Meana, Schahram Akbarian, George W Huntley, Javier González-Maeso
Antipsychotic drugs remain the standard for schizophrenia treatment. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic medications leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition remain to be elucidated. Here we demonstrate that chronic antipsychotic drug exposure increases nuclear translocation of NF-κB in both mouse and human frontal cortex, a trafficking event triggered via 5-HT2A-receptor-dependent downregulation of the NF-κB repressor IκBα...
August 7, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28758997/zika-virus-directly-infects-peripheral-neurons-and-induces-cell-death
#7
Yohan Oh, Feiran Zhang, Yaqing Wang, Emily M Lee, In Young Choi, Hotae Lim, Fahimeh Mirakhori, Ronghua Li, Luoxiu Huang, Tianlei Xu, Hao Wu, Cui Li, Cheng-Feng Qin, Zhexing Wen, Qing-Feng Wu, Hengli Tang, Zhiheng Xu, Peng Jin, Hongjun Song, Guo-Li Ming, Gabsang Lee
Zika virus (ZIKV) infection is associated with neurological disorders of both the CNS and peripheral nervous systems (PNS), yet few studies have directly examined PNS infection. Here we show that intraperitoneally or intraventricularly injected ZIKV in the mouse can infect and impact peripheral neurons in vivo. Moreover, ZIKV productively infects stem-cell-derived human neural crest cells and peripheral neurons in vitro, leading to increased cell death, transcriptional dysregulation and cell-type-specific molecular pathology...
July 31, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28758996/adults-with-autism-overestimate-the-volatility-of-the-sensory-environment
#8
Rebecca P Lawson, Christoph Mathys, Geraint Rees
Insistence on sameness and intolerance of change are among the diagnostic criteria for autism spectrum disorder (ASD), but little research has addressed how people with ASD represent and respond to environmental change. Here, behavioral and pupillometric measurements indicated that adults with ASD are less surprised than neurotypical adults when their expectations are violated, and decreased surprise is predictive of greater symptom severity. A hierarchical Bayesian model of learning suggested that in ASD, a tendency to overlearn about volatility in the face of environmental change drives a corresponding reduction in learning about probabilistically aberrant events, thus putatively rendering these events less surprising...
July 31, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28758995/dorsal-hippocampus-contributes-to-model-based-planning
#9
Kevin J Miller, Matthew M Botvinick, Carlos D Brody
Planning can be defined as action selection that leverages an internal model of the outcomes likely to follow each possible action. Its neural mechanisms remain poorly understood. Here we adapt recent advances from human research for rats, presenting for the first time an animal task that produces many trials of planned behavior per session, making multitrial rodent experimental tools available to study planning. We use part of this toolkit to address a perennially controversial issue in planning: the role of the dorsal hippocampus...
July 31, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28758999/necroptosis-activation-in-alzheimer-s-disease
#10
Antonella Caccamo, Caterina Branca, Ignazio S Piras, Eric Ferreira, Matthew J Huentelman, Winnie S Liang, Ben Readhead, Joel T Dudley, Elizabeth E Spangenberg, Kim N Green, Ramona Belfiore, Wendy Winslow, Salvatore Oddo
Alzheimer's disease (AD) is characterized by severe neuronal loss; however, the mechanisms by which neurons die remain elusive. Necroptosis, a programmed form of necrosis, is executed by the mixed lineage kinase domain-like (MLKL) protein, which is triggered by receptor-interactive protein kinases (RIPK) 1 and 3. We found that necroptosis was activated in postmortem human AD brains, positively correlated with Braak stage, and inversely correlated with brain weight and cognitive scores. In addition, we found that the set of genes regulated by RIPK1 overlapped significantly with multiple independent AD transcriptomic signatures, indicating that RIPK1 activity could explain a substantial portion of transcriptomic changes in AD...
July 24, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28758998/functional-dissection-of-signal-and-noise-in-mt-and-lip-during-decision-making
#11
Jacob L Yates, Il Memming Park, Leor N Katz, Jonathan W Pillow, Alexander C Huk
During perceptual decision-making, responses in the middle temporal (MT) and lateral intraparietal (LIP) areas appear to map onto theoretically defined quantities, with MT representing instantaneous motion evidence and LIP reflecting the accumulated evidence. However, several aspects of the transformation between the two areas have not been empirically tested. We therefore performed multistage systems identification analyses of the simultaneous activity of MT and LIP during individual decisions. We found that monkeys based their choices on evidence presented in early epochs of the motion stimulus and that substantial early weighting of motion was present in MT responses...
July 24, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28758994/high-dimensional-single-cell-characterization-of-the-brain-s-immune-compartment
#12
Ben Korin, Tamar L Ben-Shaanan, Maya Schiller, Tania Dubovik, Hilla Azulay-Debby, Nadia T Boshnak, Tamar Koren, Asya Rolls
The brain and its borders create a highly dynamic microenvironment populated with immune cells. Yet characterization of immune cells within the naive brain compartment remains limited. In this study, we used CyTOF mass cytometry to characterize the immune populations of the naive mouse brain using 44 cell surface markers. By comparing immune cell composition and cell profiles between the brain compartment and blood, we were able to characterize previously undescribed cell subsets of CD8 T cells, B cells, NK cells and dendritic cells in the naive brain...
July 24, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28714954/c9orf72-expansion-disrupts-atm-mediated-chromosomal-break-repair
#13
Callum Walker, Saul Herranz-Martin, Evangelia Karyka, Chunyan Liao, Katherine Lewis, Waheba Elsayed, Vera Lukashchuk, Shih-Chieh Chiang, Swagat Ray, Padraig J Mulcahy, Mateusz Jurga, Ioannis Tsagakis, Tommaso Iannitti, Jayanth Chandran, Ian Coldicott, Kurt J De Vos, Mohamed K Hassan, Adrian Higginbottom, Pamela J Shaw, Guillaume M Hautbergue, Mimoun Azzouz, Sherif F El-Khamisy
Hexanucleotide repeat expansions represent the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, though the mechanisms by which such expansions cause neurodegeneration are poorly understood. We report elevated levels of DNA-RNA hybrids (R-loops) and double strand breaks in rat neurons, human cells and C9orf72 ALS patient spinal cord tissues. Accumulation of endogenous DNA damage is concomitant with defective ATM-mediated DNA repair signaling and accumulation of protein-linked DNA breaks...
July 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28714953/gut-microbiota-is-critical-for-the-induction-of-chemotherapy-induced-pain
#14
Shiqian Shen, Grewo Lim, Zerong You, Weihua Ding, Peigen Huang, Chongzhao Ran, Jason Doheny, Peter Caravan, Samuel Tate, Kun Hu, Hyangin Kim, Michael McCabe, Bo Huang, Zhongcong Xie, Douglas Kwon, Lucy Chen, Jianren Mao
Chemotherapy-induced pain is a dose-limiting condition that affects 30% of patients undergoing chemotherapy. We found that gut microbiota promotes the development of chemotherapy-induced mechanical hyperalgesia. Oxaliplatin-induced mechanical hyperalgesia was reduced in germ-free mice and in mice pretreated with antibiotics. Restoring the microbiota of germ-free mice abrogated this protection. These effects appear to be mediated, in part, by TLR4 expressed on hematopoietic cells, including macrophages.
July 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28714952/a-circuit-based-mechanism-underlying-familiarity-signaling-and-the-preference-for-novelty
#15
Susanna Molas, Rubing Zhao-Shea, Liwang Liu, Steven R DeGroot, Paul D Gardner, Andrew R Tapper
Novelty preference (NP) is an evolutionarily conserved, essential survival mechanism often dysregulated in neuropsychiatric disorders. NP is mediated by a motivational dopamine signal that increases in response to novel stimuli, thereby driving exploration. However, the mechanism by which once-novel stimuli transition to familiar stimuli is unknown. Here we describe a neuroanatomical substrate for familiarity signaling, the interpeduncular nucleus (IPN) of the midbrain, which is activated as novel stimuli become familiar with multiple exposures...
July 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28714951/rates-distribution-and-implications-of-postzygotic-mosaic-mutations-in-autism-spectrum-disorder
#16
Elaine T Lim, Mohammed Uddin, Silvia De Rubeis, Yingleong Chan, Anne S Kamumbu, Xiaochang Zhang, Alissa M D'Gama, Sonia N Kim, Robert Sean Hill, Arthur P Goldberg, Christopher Poultney, Nancy J Minshew, Itaru Kushima, Branko Aleksic, Norio Ozaki, Mara Parellada, Celso Arango, Maria J Penzol, Angel Carracedo, Alexander Kolevzon, Christina M Hultman, Lauren A Weiss, Menachem Fromer, Andreas G Chiocchetti, Christine M Freitag, George M Church, Stephen W Scherer, Joseph D Buxbaum, Christopher A Walsh
We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10(-6)), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5...
July 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28692062/neural-reactivations-during-sleep-determine-network-credit-assignment
#17
Tanuj Gulati, Ling Guo, Dhakshin S Ramanathan, Anitha Bodepudi, Karunesh Ganguly
A fundamental goal of motor learning is to establish the neural patterns that produce a desired behavioral outcome. It remains unclear how and when the nervous system solves this 'credit assignment' problem. Using neuroprosthetic learning, in which we could control the causal relationship between neurons and behavior, we found that sleep-dependent processing was required for credit assignment and the establishment of task-related functional connectivity reflecting the casual neuron-behavior relationship. Notably, we observed a strong link between the microstructure of sleep reactivations and credit assignment, with downscaling of non-causal activity...
July 10, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28581480/rich-cell-type-specific-network-topology-in-neocortical-microcircuitry
#18
Eyal Gal, Michael London, Amir Globerson, Srikanth Ramaswamy, Michael W Reimann, Eilif Muller, Henry Markram, Idan Segev
Uncovering structural regularities and architectural topologies of cortical circuitry is vital for understanding neural computations. Recently, an experimentally constrained algorithm generated a dense network reconstruction of a ∼0.3-mm(3) volume from juvenile rat somatosensory neocortex, comprising ∼31,000 cells and ∼36 million synapses. Using this reconstruction, we found a small-world topology with an average of 2.5 synapses separating any two cells and multiple cell-type-specific wiring features...
June 5, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28692061/a-causal-account-of-the-brain-network-computations-underlying-strategic-social-behavior
#19
Christopher A Hill, Shinsuke Suzuki, Rafael Polania, Marius Moisa, John P O'Doherty, Christian C Ruff
During competitive interactions, humans have to estimate the impact of their own actions on their opponent's strategy. Here we provide evidence that neural computations in the right temporoparietal junction (rTPJ) and interconnected structures are causally involved in this process. By combining inhibitory continuous theta-burst transcranial magnetic stimulation with model-based functional MRI, we show that disrupting neural excitability in the rTPJ reduces behavioral and neural indices of mentalizing-related computations, as well as functional connectivity of the rTPJ with ventral and dorsal parts of the medial prefrontal cortex...
August 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28671696/spatiotemporal-profile-of-postsynaptic-interactomes-integrates-components-of-complex-brain-disorders
#20
Jing Li, Wangshu Zhang, Hui Yang, Daniel P Howrigan, Brent Wilkinson, Tade Souaiaia, Oleg V Evgrafov, Giulio Genovese, Veronica A Clementel, Jennifer C Tudor, Ted Abel, James A Knowles, Benjamin M Neale, Kai Wang, Fengzhu Sun, Marcelo P Coba
The postsynaptic density (PSD) contains a collection of scaffold proteins used for assembling synaptic signaling complexes. However, it is not known how the core-scaffold machinery associates in protein-interaction networks or how proteins encoded by genes involved in complex brain disorders are distributed through spatiotemporal protein complexes. Here using immunopurification, proteomics and bioinformatics, we isolated 2,876 proteins across 41 in vivo interactomes and determined their protein domain composition, correlation to gene expression levels and developmental integration to the PSD...
August 2017: Nature Neuroscience
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