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Nature Neuroscience

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https://www.readbyqxmd.com/read/28414333/dynamic-hidden-states-underlying-working-memory-guided-behavior
#1
Michael J Wolff, Janina Jochim, Elkan G Akyürek, Mark G Stokes
Recent theoretical models propose that working memory is mediated by rapid transitions in 'activity-silent' neural states (for example, short-term synaptic plasticity). According to the dynamic coding framework, such hidden state transitions flexibly configure memory networks for memory-guided behavior and dissolve them equally fast to allow forgetting. We developed a perturbation approach to measure mnemonic hidden states in an electroencephalogram. By 'pinging' the brain during maintenance, we show that memory-item-specific information is decodable from the impulse response, even in the absence of attention and lingering delay activity...
April 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28414332/comprehensive-transcriptome-analysis-of-neocortical-layers-in-humans-chimpanzees-and-macaques
#2
Zhisong He, Dingding Han, Olga Efimova, Patricia Guijarro, Qianhui Yu, Anna Oleksiak, Shasha Jiang, Konstantin Anokhin, Boris Velichkovsky, Stefan Grünewald, Philipp Khaitovich
While human cognitive abilities are clearly unique, underlying changes in brain organization and function remain unresolved. Here we characterized the transcriptome of the cortical layers and adjacent white matter in the prefrontal cortexes of humans, chimpanzees and rhesus macaques using unsupervised sectioning followed by RNA sequencing. More than 20% of detected genes were expressed predominantly in one layer, yielding 2,320 human layer markers. While the bulk of the layer markers were conserved among species, 376 switched their expression to another layer in humans...
April 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28414331/a-new-fate-mapping-system-reveals-context-dependent-random-or-clonal-expansion-of-microglia
#3
Tuan Leng Tay, Dominic Mai, Jana Dautzenberg, Francisco Fernández-Klett, Gen Lin, Sagar, Moumita Datta, Anne Drougard, Thomas Stempfl, Alberto Ardura-Fabregat, Ori Staszewski, Anca Margineanu, Anje Sporbert, Lars M Steinmetz, J Andrew Pospisilik, Steffen Jung, Josef Priller, Dominic Grün, Olaf Ronneberger, Marco Prinz
Microglia constitute a highly specialized network of tissue-resident immune cells that is important for the control of tissue homeostasis and the resolution of diseases of the CNS. Little is known about how their spatial distribution is established and maintained in vivo. Here we establish a new multicolor fluorescence fate mapping system to monitor microglial dynamics during steady state and disease. Our findings suggest that microglia establish a dense network with regional differences, and the high regional turnover rates found challenge the universal concept of microglial longevity...
April 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28394324/abnormal-wiring-of-cck-basket-cells-disrupts-spatial-information-coding
#4
Isabel Del Pino, Jorge R Brotons-Mas, André Marques-Smith, Aline Marighetto, Andreas Frick, Oscar Marín, Beatriz Rico
The function of cortical GABAergic interneurons is largely determined by their integration into specific neural circuits, but the mechanisms controlling the wiring of these cells remain largely unknown. This is particularly true for a major population of basket cells that express the neuropeptide cholecystokinin (CCK). Here we found that the tyrosine kinase receptor ErbB4 was required for the normal integration into cortical circuits of basket cells expressing CCK and vesicular glutamate transporter 3 (VGlut3)...
April 10, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28394323/sharp-wave-ripples-during-learning-stabilize-the-hippocampal-spatial-map
#5
Lisa Roux, Bo Hu, Ronny Eichler, Eran Stark, György Buzsáki
Cognitive representation of the environment requires a stable hippocampal map, but the mechanisms maintaining a given map are unknown. Because sharp wave-ripples (SPW-R) orchestrate both retrospective and prospective spatial information, we hypothesized that disrupting neuronal activity during SPW-Rs affects spatial representation. Mice learned new sets of three goal locations daily in a multiwell maze. We used closed-loop SPW-R detection at goal locations to trigger optogenetic silencing of a subset of CA1 pyramidal neurons...
April 10, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28394322/the-neural-correlates-of-dreaming
#6
Francesca Siclari, Benjamin Baird, Lampros Perogamvros, Giulio Bernardi, Joshua J LaRocque, Brady Riedner, Melanie Boly, Bradley R Postle, Giulio Tononi
Consciousness never fades during waking. However, when awakened from sleep, we sometimes recall dreams and sometimes recall no experiences. Traditionally, dreaming has been identified with rapid eye-movement (REM) sleep, characterized by wake-like, globally 'activated', high-frequency electroencephalographic activity. However, dreaming also occurs in non-REM (NREM) sleep, characterized by prominent low-frequency activity. This challenges our understanding of the neural correlates of conscious experiences in sleep...
April 10, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28368385/dopamine-transients-are-sufficient-and-necessary-for-acquisition-of-model-based-associations
#7
Melissa J Sharpe, Chun Yun Chang, Melissa A Liu, Hannah M Batchelor, Lauren E Mueller, Joshua L Jones, Yael Niv, Geoffrey Schoenbaum
Associative learning is driven by prediction errors. Dopamine transients correlate with these errors, which current interpretations limit to endowing cues with a scalar quantity reflecting the value of future rewards. We tested whether dopamine might act more broadly to support learning of an associative model of the environment. Using sensory preconditioning, we show that prediction errors underlying stimulus-stimulus learning can be blocked behaviorally and reinstated by optogenetically activating dopamine neurons...
April 3, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28368384/glp-1-acts-on-habenular-avoidance-circuits-to-control-nicotine-intake
#8
Luis M Tuesta, Zuxin Chen, Alexander Duncan, Christie D Fowler, Masago Ishikawa, Brian R Lee, Xin-An Liu, Qun Lu, Michael Cameron, Matthew R Hayes, Theodore M Kamenecka, Matthew Pletcher, Paul J Kenny
Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake...
April 3, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346453/activity-induced-histone-modifications-govern-neurexin-1-mrna-splicing-and-memory-preservation
#9
Xinlu Ding, Sanxiong Liu, Miaomiao Tian, Wenhao Zhang, Tao Zhu, Dongdong Li, Jiawei Wu, HaiTeng Deng, Yichang Jia, Wei Xie, Hong Xie, Ji-Song Guan
Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346452/purine-synthesis-promotes-maintenance-of-brain-tumor-initiating-cells-in-glioma
#10
Xiuxing Wang, Kailin Yang, Qi Xie, Qiulian Wu, Stephen C Mack, Yu Shi, Leo J Y Kim, Briana C Prager, William A Flavahan, Xiaojing Liu, Meromit Singer, Christopher G Hubert, Tyler E Miller, Wenchao Zhou, Zhi Huang, Xiaoguang Fang, Aviv Regev, Mario L Suvà, Tae Hyun Hwang, Jason W Locasale, Shideng Bao, Jeremy N Rich
Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28319610/capillary-k-sensing-initiates-retrograde-hyperpolarization-to-increase-local-cerebral-blood-flow
#11
Thomas A Longden, Fabrice Dabertrand, Masayo Koide, Albert L Gonzales, Nathan R Tykocki, Joseph E Brayden, David Hill-Eubanks, Mark T Nelson
Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K(+) -a byproduct of neural activity-which activates capillary endothelial cell inward-rectifier K(+) (KIR2...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28319609/developmental-alterations-in-huntington-s-disease-neural-cells-and-pharmacological-rescue-in-cells-and-mice
#12
(no author information available yet)
Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28319608/cerebellar-granule-cells-acquire-a-widespread-predictive-feedback-signal-during-motor-learning
#13
Andrea Giovannucci, Aleksandra Badura, Ben Deverett, Farzaneh Najafi, Talmo D Pereira, Zhenyu Gao, Ilker Ozden, Alexander D Kloth, Eftychios Pnevmatikakis, Liam Paninski, Chris I De Zeeuw, Javier F Medina, Samuel S-H Wang
Cerebellar granule cells, which constitute half the brain's neurons, supply Purkinje cells with contextual information necessary for motor learning, but how they encode this information is unknown. Here we show, using two-photon microscopy to track neural activity over multiple days of cerebellum-dependent eyeblink conditioning in mice, that granule cell populations acquire a dense representation of the anticipatory eyelid movement. Initially, granule cells responded to neutral visual and somatosensory stimuli as well as periorbital airpuffs used for training...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28288128/%C3%AE-synuclein-promotes-dilation-of-the-exocytotic-fusion-pore
#14
Todd Logan, Jacob Bendor, Chantal Toupin, Kurt Thorn, Robert H Edwards
The protein α-synuclein has a central role in the pathogenesis of Parkinson's disease. Like that of other proteins that accumulate in neurodegenerative disease, however, the function of α-synuclein remains unknown. Localization to the nerve terminal suggests a role in neurotransmitter release, and overexpression inhibits regulated exocytosis, but previous work has failed to identify a clear physiological defect in mice lacking all three synuclein isoforms. Using adrenal chromaffin cells and neurons, we now find that both overexpressed and endogenous synuclein accelerate the kinetics of individual exocytotic events, promoting cargo discharge and reducing pore closure ('kiss-and-run')...
March 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28288127/the-effect-of-face-patch-microstimulation-on-perception-of-faces-and-objects
#15
Sebastian Moeller, Trinity Crapse, Le Chang, Doris Y Tsao
What is the range of stimuli encoded by face-selective regions of the brain? We asked how electrical microstimulation of face patches in macaque inferotemporal cortex affects perception of faces and objects. We found that microstimulation strongly distorted face percepts and that this effect depended on precise targeting to the center of face patches. While microstimulation had no effect on the percept of many non-face objects, it did affect the percept of some, including non-face objects whose shape is consistent with a face (for example, apples) as well as somewhat facelike abstract images (for example, cartoon houses)...
March 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28288126/manipulating-fear-associations-via-optogenetic-modulation-of-amygdala-inputs-to-prefrontal-cortex
#16
Oded Klavir, Matthias Prigge, Ayelet Sarel, Rony Paz, Ofer Yizhar
Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA-mPFC inputs is not yet clear...
March 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28288125/regulatory-t-cells-promote-myelin-regeneration-in-the-central-nervous-system
#17
Yvonne Dombrowski, Thomas O'Hagan, Marie Dittmer, Rosana Penalva, Sonia R Mayoral, Peter Bankhead, Samara Fleville, George Eleftheriadis, Chao Zhao, Michelle Naughton, Rachel Hassan, Jill Moffat, John Falconer, Amanda Boyd, Peter Hamilton, Ingrid V Allen, Adrien Kissenpfennig, Paul N Moynagh, Emma Evergren, Bernard Perbal, Anna C Williams, Rebecca J Ingram, Jonah R Chan, Robin J M Franklin, Denise C Fitzgerald
Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination. Treg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of Treg...
March 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28288124/c1-neurons-mediate-a-stress-induced-anti-inflammatory-reflex-in-mice
#18
Chikara Abe, Tsuyoshi Inoue, Mabel A Inglis, Kenneth E Viar, Liping Huang, Hong Ye, Diane L Rosin, Ruth L Stornetta, Mark D Okusa, Patrice G Guyenet
C1 neurons, located in the medulla oblongata, mediate adaptive autonomic responses to physical stressors (for example, hypotension, hemorrhage and presence of lipopolysaccharides). We describe here a powerful anti-inflammatory effect of restraint stress, mediated by C1 neurons: protection against renal ischemia-reperfusion injury. Restraint stress or optogenetic C1 neuron (C1) stimulation (10 min) protected mice from ischemia-reperfusion injury (IRI). The protection was reproduced by injecting splenic T cells that had been preincubated with noradrenaline or splenocytes harvested from stressed mice...
March 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28263302/whole-genome-sequencing-resource-identifies-18-new-candidate-genes-for-autism-spectrum-disorder
#19
Ryan K C Yuen, Daniele Merico, Matt Bookman, Jennifer L Howe, Bhooma Thiruvahindrapuram, Rohan V Patel, Joe Whitney, Nicole Deflaux, Jonathan Bingham, Zhuozhi Wang, Giovanna Pellecchia, Janet A Buchanan, Susan Walker, Christian R Marshall, Mohammed Uddin, Mehdi Zarrei, Eric Deneault, Lia D'Abate, Ada J S Chan, Stephanie Koyanagi, Tara Paton, Sergio L Pereira, Ny Hoang, Worrawat Engchuan, Edward J Higginbotham, Karen Ho, Sylvia Lamoureux, Weili Li, Jeffrey R MacDonald, Thomas Nalpathamkalam, Wilson W L Sung, Fiona J Tsoi, John Wei, Lizhen Xu, Anne-Marie Tasse, Emily Kirby, William Van Etten, Simon Twigger, Wendy Roberts, Irene Drmic, Sanne Jilderda, Bonnie MacKinnon Modi, Barbara Kellam, Michael Szego, Cheryl Cytrynbaum, Rosanna Weksberg, Lonnie Zwaigenbaum, Marc Woodbury-Smith, Jessica Brian, Lili Senman, Alana Iaboni, Krissy Doyle-Thomas, Ann Thompson, Christina Chrysler, Jonathan Leef, Tal Savion-Lemieux, Isabel M Smith, Xudong Liu, Rob Nicolson, Vicki Seifer, Angie Fedele, Edwin H Cook, Stephen Dager, Annette Estes, Louise Gallagher, Beth A Malow, Jeremy R Parr, Sarah J Spence, Jacob Vorstman, Brendan J Frey, James T Robinson, Lisa J Strug, Bridget A Fernandez, Mayada Elsabbagh, Melissa T Carter, Joachim Hallmayer, Bartha M Knoppers, Evdokia Anagnostou, Peter Szatmari, Robert H Ring, David Glazer, Mathew T Pletcher, Stephen W Scherer
We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject...
March 6, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28263300/a-distinct-entorhinal-cortex-to-hippocampal-ca1-direct-circuit-for-olfactory-associative-learning
#20
Yiding Li, Jiamin Xu, Yafeng Liu, Jia Zhu, Nan Liu, Wenbo Zeng, Ning Huang, Malte J Rasch, Haifei Jiang, Xiang Gu, Xiang Li, Minhua Luo, Chengyu Li, Junlin Teng, Jianguo Chen, Shaoqun Zeng, Longnian Lin, Xiaohui Zhang
Lateral and medial parts of entorhinal cortex (EC) convey nonspatial 'what' and spatial 'where' information, respectively, into hippocampal CA1, via both the indirect EC layer 2→ hippocampal dentate gyrus→CA3→CA1 and the direct EC layer 3→CA1 paths. However, it remains elusive how the direct path transfers distinct information and contributes to hippocampal learning functions. Here we report that lateral EC projection neurons selectively form direct excitatory synapses onto a subpopulation of morphologically complex, calbindin-expressing pyramidal cells (PCs) in the dorsal CA1 (dCA1), while medial EC neurons uniformly innervate all dCA1 PCs...
March 6, 2017: Nature Neuroscience
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