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Nature Neuroscience

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https://www.readbyqxmd.com/read/28920936/dopamine-induces-soluble-%C3%AE-synuclein-oligomers-and-nigrostriatal-degeneration
#1
Danielle E Mor, Elpida Tsika, Joseph R Mazzulli, Neal S Gould, Hanna Kim, Malcolm J Daniels, Shachee Doshi, Preetika Gupta, Jennifer L Grossman, Victor X Tan, Robert G Kalb, Kim A Caldwell, Guy A Caldwell, John H Wolfe, Harry Ischiropoulos
Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28920935/spinal-cord-injury-induced-immunodeficiency-is-mediated-by-a-sympathetic-neuroendocrine-adrenal-reflex
#2
Harald Prüss, Andrea Tedeschi, Aude Thiriot, Lydia Lynch, Scott M Loughhead, Susanne Stutte, Irina B Mazo, Marcel A Kopp, Benedikt Brommer, Christian Blex, Laura-Christin Geurtz, Thomas Liebscher, Andreas Niedeggen, Ulrich Dirnagl, Frank Bradke, Magdalena S Volz, Michael J DeVivo, Yuying Chen, Ulrich H von Andrian, Jan M Schwab
Acute spinal cord injury (SCI) causes systemic immunosuppression and life-threatening infections, thought to result from noradrenergic overactivation and excess glucocorticoid release via hypothalamus-pituitary-adrenal axis stimulation. Instead of consecutive hypothalamus-pituitary-adrenal axis activation, we report that acute SCI in mice induced suppression of serum norepinephrine and concomitant increase in cortisol, despite suppressed adrenocorticotropic hormone, indicating primary (adrenal) hypercortisolism...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28920934/esr1-cells-in-the-ventromedial-hypothalamus-control-female-aggression
#3
Koichi Hashikawa, Yoshiko Hashikawa, Robin Tremblay, Jiaxing Zhang, James E Feng, Alexander Sabol, Walter T Piper, Hyosang Lee, Bernardo Rudy, Dayu Lin
As an essential means of resolving conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor-α (Esr1) and progesterone receptor are essential for male but not female mouse aggression. In contrast, here we show that VMHvl(Esr1+) cells are indispensable for female aggression. This population was active when females attacked naturally...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28920933/modular-organization-of-the-brainstem-noradrenaline-system-coordinates-opposing-learning-states
#4
Akira Uematsu, Bao Zhen Tan, Edgar A Ycu, Jessica Sulkes Cuevas, Jenny Koivumaa, Felix Junyent, Eric J Kremer, Ilana B Witten, Karl Deisseroth, Joshua P Johansen
Noradrenaline modulates global brain states and diverse behaviors through what is traditionally believed to be a homogeneous cell population in the brainstem locus coeruleus (LC). However, it is unclear how LC coordinates disparate behavioral functions. We report a modular LC organization in rats, endowed with distinct neural projection patterns and coding properties for flexible specification of opposing behavioral learning states. LC projection mapping revealed functionally distinct cell modules with specific anatomical connectivity...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28920932/a-pathway-from-midcingulate-cortex-to-posterior-insula-gates-nociceptive-hypersensitivity
#5
Linette Liqi Tan, Patric Pelzer, Céline Heinl, Wannan Tang, Vijayan Gangadharan, Herta Flor, Rolf Sprengel, Thomas Kuner, Rohini Kuner
The identity of cortical circuits mediating nociception and pain is largely unclear. The cingulate cortex is consistently activated during pain, but the functional specificity of cingulate divisions, the roles at distinct temporal phases of central plasticity and the underlying circuitry are unknown. Here we show in mice that the midcingulate division of the cingulate cortex (MCC) does not mediate acute pain sensation and pain affect, but gates sensory hypersensitivity by acting in a wide cortical and subcortical network...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28892058/glia-specific-enhancers-and-chromatin-structure-regulate-nfia-expression-and-glioma-tumorigenesis
#6
Stacey M Glasgow, Jeffrey C Carlson, Wenyi Zhu, Lesley S Chaboub, Peng Kang, Hyun Kyoung Lee, Yoanne M Clovis, Brittney E Lozzi, Robert J McEvilly, Michael G Rosenfeld, Chad J Creighton, Soo-Kyung Lee, Carrie A Mohila, Benjamin Deneen
Long-range enhancer interactions critically regulate gene expression, yet little is known about how their coordinated activities contribute to CNS development or how this may, in turn, relate to disease states. By examining the regulation of the transcription factor NFIA in the developing spinal cord, we identified long-range enhancers that recapitulate NFIA expression across glial and neuronal lineages in vivo. Complementary genetic studies found that Sox9-Brn2 and Isl1-Lhx3 regulate enhancer activity and NFIA expression in glial and neuronal populations...
September 11, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28892057/reactivations-of-emotional-memory-in-the-hippocampus-amygdala-system-during-sleep
#7
Gabrielle Girardeau, Ingrid Inema, György Buzsáki
The consolidation of context-dependent emotional memory requires communication between the hippocampus and the basolateral amygdala (BLA), but the mechanisms of this process are unknown. We recorded neuronal ensembles in the hippocampus and BLA while rats learned the location of an aversive air puff on a linear track, as well as during sleep before and after training. We found coordinated reactivations between the hippocampus and the BLA during non-REM sleep following training. These reactivations peaked during hippocampal sharp wave-ripples (SPW-Rs) and involved a subgroup of BLA cells positively modulated during hippocampal SPW-Rs...
September 11, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28869584/an-xqtl-map-integrates-the-genetic-architecture-of-the-human-brain-s-transcriptome-and-epigenome
#8
Bernard Ng, Charles C White, Hans-Ulrich Klein, Solveig K Sieberts, Cristin McCabe, Ellis Patrick, Jishu Xu, Lei Yu, Chris Gaiteri, David A Bennett, Sara Mostafavi, Philip L De Jager
We report a multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation and histone acetylation data from the dorsolateral prefrontal cortex of 411 older adults who have all three data types. We identify SNPs significantly associated with gene expression, DNA methylation and histone modification levels. Many of these SNPs influence multiple molecular features, and we demonstrate that SNP effects on RNA expression are fully mediated by epigenetic features in 9% of these loci...
September 4, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28869583/parallel-encoding-of-recent-visual-experience-and-self-motion-during-navigation-in-drosophila
#9
Hiroshi M Shiozaki, Hokto Kazama
Animal navigation requires multiple types of information for decisions on directional heading. We identified neural processing channels that encode multiple cues during navigational decision-making in Drosophila melanogaster. In a flight simulator, we found that flies made directional choices on the basis of the location of a recently presented landmark. This experience-guided navigation was impaired by silencing neurons in the bulb (BU), a region in the central brain. Two-photon calcium imaging during flight revealed that the dorsal part of the BU encodes the location of a recent landmark, whereas the ventral part of the BU tracks self-motion reflecting turns...
September 4, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28869582/impaired-hippocampal-place-cell-dynamics-in-a-mouse-model-of-the-22q11-2-deletion
#10
Jeffrey D Zaremba, Anastasia Diamantopoulou, Nathan B Danielson, Andres D Grosmark, Patrick W Kaifosh, John C Bowler, Zhenrui Liao, Fraser T Sparks, Joseph A Gogos, Attila Losonczy
Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca(2+) imaging in hippocampal area CA1 of wild-type and Df(16)A(+/-) mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location...
September 4, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28869581/seeing-faces-is-necessary-for-face-domain-formation
#11
Michael J Arcaro, Peter F Schade, Justin L Vincent, Carlos R Ponce, Margaret S Livingstone
Here we report that monkeys raised without exposure to faces did not develop face domains, but did develop domains for other categories and did show normal retinotopic organization, indicating that early face deprivation leads to a highly selective cortical processing deficit. Therefore, experience must be necessary for the formation (or maintenance) of face domains. Gaze tracking revealed that control monkeys looked preferentially at faces, even at ages prior to the emergence of face domains, but face-deprived monkeys did not, indicating that face looking is not innate...
September 4, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28846083/glia-initiate-brain-assembly-through-noncanonical-chimaerin-furin-axon-guidance-in-c-elegans
#12
Georgia Rapti, Chang Li, Alan Shan, Yun Lu, Shai Shaham
Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals...
August 28, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28846082/memory-reactivation-improves-visual-perception
#13
Rotem Amar-Halpert, Rony Laor-Maayany, Shlomi Nemni, Jonathan D Rosenblatt, Nitzan Censor
Human perception thresholds can improve through learning. Here we report findings challenging the fundamental 'practice makes perfect' basis of procedural learning theory, showing that brief reactivations of encoded visual memories are sufficient to improve perceptual discrimination thresholds. Learning was comparable to standard practice-induced learning and was not due to short training per se, nor to an epiphenomenon of primed retrieval enhancement. The results demonstrate that basic perceptual functions can be substantially improved by memory reactivation, supporting a new account of perceptual learning dynamics...
August 28, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28846081/microglia-turnover-with-aging-and-in-an-alzheimer-s-model-via-long-term-in-vivo-single-cell-imaging
#14
Petra Füger, Jasmin K Hefendehl, Karthik Veeraraghavalu, Ann-Christin Wendeln, Christine Schlosser, Ulrike Obermüller, Bettina M Wegenast-Braun, Jonas J Neher, Peter Martus, Shinichi Kohsaka, Martin Thunemann, Robert Feil, Sangram S Sisodia, Angelos Skodras, Mathias Jucker
To clarify the role of microglia in brain homeostasis and disease, an understanding of their maintenance, proliferation and turnover is essential. The lifespan of brain microglia, however, remains uncertain, and reflects confounding factors in earlier assessments that were largely indirect. We genetically labeled single resident microglia in living mice and then used multiphoton microscopy to monitor these cells over time. Under homeostatic conditions, we found that neocortical resident microglia were long-lived, with a median lifetime of well over 15 months; thus, approximately half of these cells survive the entire mouse lifespan...
August 28, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28825719/central-amygdala-circuits-modulate-food-consumption-through-a-positive-valence-mechanism
#15
Amelia M Douglass, Hakan Kucukdereli, Marion Ponserre, Milica Markovic, Jan Gründemann, Cornelia Strobel, Pilar L Alcala Morales, Karl-Klaus Conzelmann, Andreas Lüthi, Rüdiger Klein
The complex behaviors underlying reward seeking and consumption are integral to organism survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is poorly understood. The central nucleus of the amygdala (CeA) has been implicated in feeding and reward, but the neurons and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we defined the neuronal mechanisms by which CeA neurons promote food consumption...
August 21, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28825718/selective-inhibitory-control-of-pyramidal-neuron-ensembles-and-cortical-subnetworks-by-chandelier-cells
#16
Jiangteng Lu, Jason Tucciarone, Nancy Padilla-Coreano, Miao He, Joshua A Gordon, Z Josh Huang
The neocortex comprises multiple information processing streams mediated by subsets of glutamatergic pyramidal cells (PCs) that receive diverse inputs and project to distinct targets. How GABAergic interneurons regulate the segregation and communication among intermingled PC subsets that contribute to separate brain networks remains unclear. Here we demonstrate that a subset of GABAergic chandelier cells (ChCs) in the prelimbic cortex, which innervate PCs at spike initiation site, selectively control PCs projecting to the basolateral amygdala (BLAPC) compared to those projecting to contralateral cortex (CCPC)...
August 21, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28805816/selective-attention-within-the-foveola
#17
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
#18
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
#19
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
#20
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
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