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Neuron

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https://www.readbyqxmd.com/read/28803732/reck-and-gpr124-are-essential-receptor-cofactors-for-wnt7a-wnt7b-specific-signaling-in-mammalian-cns-angiogenesis-and-blood-brain-barrier-regulation
#1
Chris Cho, Philip M Smallwood, Jeremy Nathans
Reck, a GPI-anchored membrane protein, and Gpr124, an orphan GPCR, have been implicated in Wnt7a/Wnt7b signaling in the CNS vasculature. We show here that vascular endothelial cell (EC)-specific reduction in Reck impairs CNS angiogenesis and that EC-specific postnatal loss of Reck, combined with loss of Norrin, impairs blood-brain barrier (BBB) maintenance. The most N-terminal domain of Reck binds to the leucine-rich repeat (LRR) and immunoglobulin (Ig) domains of Gpr124, and weakening this interaction by targeted mutagenesis reduces Reck/Gpr124 stimulation of Wnt7a signaling in cell culture and impairs CNS angiogenesis...
August 7, 2017: Neuron
https://www.readbyqxmd.com/read/28817806/specialized-mechanosensory-nociceptors-mediating-rapid-responses-to-hair-pull
#2
Nima Ghitani, Arnab Barik, Marcin Szczot, James H Thompson, Chia Li, Claire E Le Pichon, Michael J Krashes, Alexander T Chesler
The somatosensory system provides animals with the ability to detect, distinguish, and respond to diverse thermal, mechanical, and irritating stimuli. While there has been progress in defining classes of neurons underlying temperature sensation and gentle touch, less is known about the neurons specific for mechanical pain. Here, we use in vivo functional imaging to identify a class of cutaneous sensory neurons that are selectively activated by high-threshold mechanical stimulation (HTMRs). We show that their optogenetic excitation evokes rapid protective and avoidance behaviors...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817805/ltp-at-hilar-mossy-cell-dentate-granule-cell-synapses-modulates-dentate-gyrus-output-by-increasing-excitation-inhibition-balance
#3
Yuki Hashimotodani, Kaoutsar Nasrallah, Kyle R Jensen, Andrés E Chávez, Daniel Carrera, Pablo E Castillo
Excitatory hilar mossy cells (MCs) in the dentate gyrus receive inputs from dentate granule cells (GCs) and project back to GCs locally, contralaterally, and along the longitudinal axis of the hippocampus, thereby establishing an associative positive-feedback loop and connecting functionally diverse hippocampal areas. MCs also synapse with GABAergic interneurons that mediate feed-forward inhibition onto GCs. Surprisingly, although these circuits have been implicated in both memory formation (e.g., pattern separation) and temporal lobe epilepsy, little is known about activity-dependent plasticity of their synaptic connections...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817804/structural-mechanism-for-modulation-of-synaptic-neuroligin-neurexin-signaling-by-mdga-proteins
#4
Jonathan Elegheert, Vedrana Cvetkovska, Amber J Clayton, Christina Heroven, Kristel M Vennekens, Samuel N Smukowski, Michael C Regan, Wanyi Jia, Alexandra C Smith, Hiro Furukawa, Jeffrey N Savas, Joris de Wit, Jo Begbie, Ann Marie Craig, A Radu Aricescu
Neuroligin-neurexin (NL-NRX) complexes are fundamental synaptic organizers in the central nervous system. An accurate spatial and temporal control of NL-NRX signaling is crucial to balance excitatory and inhibitory neurotransmission, and perturbations are linked with neurodevelopmental and psychiatric disorders. MDGA proteins bind NLs and control their function and interaction with NRXs via unknown mechanisms. Here, we report crystal structures of MDGA1, the NL1-MDGA1 complex, and a spliced NL1 isoform. Two large, multi-domain MDGA molecules fold into rigid triangular structures, cradling a dimeric NL to prevent NRX binding...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817803/developmental-dysfunction-of-vip-interneurons-impairs-cortical-circuits
#5
Renata Batista-Brito, Martin Vinck, Katie A Ferguson, Jeremy T Chang, David Laubender, Gyorgy Lur, James M Mossner, Victoria G Hernandez, Charu Ramakrishnan, Karl Deisseroth, Michael J Higley, Jessica A Cardin
GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation. Using a conditional ErbB4 deletion, we tested the role of vasoactive intestinal peptide (VIP)-expressing interneurons in the postnatal maturation of cortical circuits in vivo. ErbB4 removal from VIP interneurons during development leads to changes in their activity, along with severe dysregulation of cortical temporal organization and state dependence...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817802/molecular-memory-of-morphologies-by-septins-during-neuron-generation-allows-early-polarity-inheritance
#6
Leila Boubakar, Julien Falk, Hugo Ducuing, Karine Thoinet, Florie Reynaud, Edmund Derrington, Valérie Castellani
Transmission of polarity established early during cell lineage history is emerging as a key process guiding cell differentiation. Highly polarized neurons provide a fascinating model to study inheritance of polarity over cell generations and across morphological transitions. Neural crest cells (NCCs) migrate to the dorsal root ganglia to generate neurons directly or after cell divisions in situ. Using live imaging of vertebrate embryo slices, we found that bipolar NCC progenitors lose their polarity, retracting their processes to round for division, but generate neurons with bipolar morphology by emitting processes from the same locations as the progenitor...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817801/a-sensitized-igf1-treatment-restores-corticospinal-axon-dependent-functions
#7
Yuanyuan Liu, Xuhua Wang, Wenlei Li, Qian Zhang, Yi Li, Zicong Zhang, Junjie Zhu, Bo Chen, Philip R Williams, Yiming Zhang, Bin Yu, Xiaosong Gu, Zhigang He
A major hurdle for functional recovery after both spinal cord injury and cortical stroke is the limited regrowth of the axons in the corticospinal tract (CST) that originate in the motor cortex and innervate the spinal cord. Despite recent advances in engaging the intrinsic mechanisms that control CST regrowth, it remains to be tested whether such methods can promote functional recovery in translatable settings. Here we show that post-lesional AAV-assisted co-expression of two soluble proteins, namely insulin-like growth factor 1 (IGF1) and osteopontin (OPN), in cortical neurons leads to robust CST regrowth and the recovery of CST-dependent behavioral performance after both T10 lateral spinal hemisection and a unilateral cortical stroke...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817800/tia1-mutations-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-promote-phase-separation-and-alter-stress-granule-dynamics
#8
Ian R Mackenzie, Alexandra M Nicholson, Mohona Sarkar, James Messing, Maria D Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B Perkerson, Aishe Kurti, Billie J Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R Hsiung, Charles Krieger, Melissa E Murray, Masato Kato, John D Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A Zivkovic, Veronica Hirsch-Reinshagen, Raymond P Roos, Stephan Züchner, Neill R Graff-Radford, Ronald C Petersen, Richard J Caselli, Zbigniew K Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B Boylan, J Paul Taylor, Rosa Rademakers
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10(-6)). Postmortem neuropathology of five TIA1 mutations carriers showed a consistent pathological signature with numerous round, hyaline, TAR DNA-binding protein 43 (TDP-43)-positive inclusions...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817799/human-astrocyte-maturation-captured-in-3d-cerebral-cortical-spheroids-derived-from-pluripotent-stem-cells
#9
Steven A Sloan, Spyros Darmanis, Nina Huber, Themasap A Khan, Fikri Birey, Christine Caneda, Richard Reimer, Stephen R Quake, Ben A Barres, Sergiu P Paşca
There is significant need to develop physiologically relevant models for investigating human astrocytes in health and disease. Here, we present an approach for generating astrocyte lineage cells in a three-dimensional (3D) cytoarchitecture using human cerebral cortical spheroids (hCSs) derived from pluripotent stem cells. We acutely purified astrocyte-lineage cells from hCSs at varying stages up to 20 months in vitro using immunopanning and cell sorting and performed high-depth bulk and single-cell RNA sequencing to directly compare them to purified primary human brain cells...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817798/toward-a-wiring-diagram-understanding-of-appetite-control
#10
REVIEW
Mark L Andermann, Bradford B Lowell
Prior mouse genetic research has set the stage for a deep understanding of appetite regulation. This goal is now being realized through the use of recent technological advances, such as the ability to map connectivity between neurons, manipulate neural activity in real time, and measure neural activity during behavior. Indeed, major progress has been made with regard to meal-related gut control of appetite, arcuate nucleus-based hypothalamic circuits linking energy state to the motivational drive, hunger, and, finally, limbic and cognitive processes that bring about hunger-mediated increases in reward value and perception of food...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817797/wrapped-to-adapt-experience-dependent-myelination
#11
REVIEW
Christopher W Mount, Michelle Monje
Activity of the nervous system has long been recognized as a critical modulator of brain structure and function. Influences of experience on the cytoarchitecture and functional connectivity of neurons have been appreciated since the classic work of Hubel and Wiesel (1963; Wiesel and Hubel, 1963a, 1963b). In recent years, a similar structural plasticity has come to light for the myelinated infrastructure of the nervous system. While an innate program of myelin development proceeds independently of nervous system activity, increasing evidence supports a role for activity-dependent, plastic changes in myelin-forming cells that influence myelin structure and neurological function...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817796/the-strange-case-of-aggression-and-the-brain
#12
Vinicius M A Carvalho, Thiago S Nakahara, Fabio Papes
Territorial male mice are aggressive toward intruding males, but socially bonded males are not. Through manipulation of activity in a subset of neurons in the ventromedial hypothalamus, Yang et al. (2017) report that social and physiological factors non-linearly interact to control male aggression.
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817795/hippocampal-dentate-mossy-cells-improve-their-cv-and-trk-into-the-limelight
#13
Aaron D Milstein, Ivan Soltesz
The impact of dentate mossy cells on hippocampal activity remained uncertain despite a long history of investigation. In this issue of Neuron, Hashimotodani et al. (2017) discover a presynaptically expressed form of long-term potentiation at mossy cell outputs, shedding light on their mysterious function.
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817794/a-triad-of-crystals-sheds-light-on-mdga-interference-with-neuroligation
#14
Olivier Thoumine, Pascale Marchot
Neurexins and neuroligins form trans-synaptic complexes that promote synapse development. In this issue of Neuron, Aricescu and colleagues (Elegheert et al., 2017) complement and strengthen two recent reports by the Kim and Rudenko teams (Kim et al., 2017; Gangwar et al., 2017) to dissect the molecular determinants by which MDGAs challenge the neurexin-neuroligin partnership.
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817793/precision-neuroscience-dense-sampling-of-individual-brains
#15
Russell A Poldrack
In this issue, Gordon et al. (2017) use dense sampling of resting and task fMRI within individuals to demonstrate that patterns of correlation in resting fMRI are closely aligned with functional architecture as identified using task fMRI.
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817792/making-human-stars-a-new-method-to-generate-human-astrocytes
#16
Nicola J Allen
Human astrocytes are increasingly appreciated as important contributors to brain function in health and disease, but techniques to study them are limited. In this issue of Neuron, Sloan and colleagues (2017) describe a new 3D culture model that generates mature human astrocytes, opening the door to future studies of their function.
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28781169/satb1-regulates-contactin-5-to-pattern-dendrites-of-a-mammalian-retinal-ganglion-cell
#17
Yi-Rong Peng, Nicholas M Tran, Arjun Krishnaswamy, Dimitar Kostadinov, Emily M Martersteck, Joshua R Sanes
The size and shape of dendritic arbors are prime determinants of neuronal connectivity and function. We asked how ON-OFF direction-selective ganglion cells (ooDSGCs) in mouse retina acquire their bistratified dendrites, in which responses to light onset and light offset are segregated to distinct strata. We found that the transcriptional regulator Satb1 is selectively expressed by ooDSGCs. In Satb1 mutant mice, ooDSGC dendrites lack ON arbors, and the cells selectively lose ON responses. Satb1 regulates expression of a homophilic adhesion molecule, Contactin 5 (Cntn5)...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28781168/rna-docking-and-local-translation-regulate-site-specific-axon-remodeling-in%C3%A2-vivo
#18
Hovy Ho-Wai Wong, Julie Qiaojin Lin, Florian Ströhl, Cláudio Gouveia Roque, Jean-Michel Cioni, Roberta Cagnetta, Benita Turner-Bridger, Romain F Laine, William A Harris, Clemens F Kaminski, Christine E Holt
Nascent proteins can be positioned rapidly at precise subcellular locations by local protein synthesis (LPS) to facilitate localized growth responses. Axon arbor architecture, a major determinant of synaptic connectivity, is shaped by localized growth responses, but it is unknown whether LPS influences these responses in vivo. Using high-resolution live imaging, we examined the spatiotemporal dynamics of RNA and LPS in retinal axons during arborization in vivo. Endogenous RNA tracking reveals that RNA granules dock at sites of branch emergence and invade stabilized branches...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28781167/cross-compartmental-modulation-of-dendritic-signals-for-retinal-direction-selectivity
#19
David Koren, James C R Grove, Wei Wei
Compartmentalized signaling in dendritic subdomains is critical for the function of many central neurons. In the retina, individual dendritic sectors of a starburst amacrine cell (SAC) are preferentially activated by different directions of linear motion, indicating limited signal propagation between the sectors. However, the mechanism that regulates this propagation is poorly understood. Here, we find that metabotropic glutamate receptor 2 (mGluR2) signaling, which acts on voltage-gated calcium channels in SACs, selectively restricts cross-sector signal propagation in SACs, but does not affect local dendritic computation within individual sectors...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28757306/functional-subpopulations-of-neurons-in-a-macaque-face-patch-revealed-by-single-unit-fmri-mapping
#20
Soo Hyun Park, Brian E Russ, David B T McMahon, Kenji W Koyano, Rebecca A Berman, David A Leopold
Neurons within fMRI-defined face patches of the macaque brain exhibit shared categorical responses to flashed images but diverge in their responses under more natural viewing conditions. Here we investigate functional diversity among neurons in the anterior fundus (AF) face patch, combining whole-brain fMRI with longitudinal single-unit recordings in a local population (<1 mm(3)). For each cell, we computed a whole-brain correlation map based on its shared time course with voxels throughout the brain during naturalistic movie viewing...
August 16, 2017: Neuron
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