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Neuron

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https://www.readbyqxmd.com/read/27916455/phosphodiesterase-10a-inhibition-improves-cortico-basal-ganglia-function-in-huntington-s-disease-models
#1
Vahri Beaumont, Sheng Zhong, Hai Lin, WenJin Xu, Amyaouch Bradaia, Esther Steidl, Melanie Gleyzes, Kristian Wadel, Bruno Buisson, Fernando E Padovan-Neto, Shreaya Chakroborty, Karen M Ward, John F Harms, Jose Beltran, Mei Kwan, Afshin Ghavami, Jenny Häggkvist, Miklós Tóth, Christer Halldin, Andrea Varrone, Christoph Schaab, J Nikolaj Dybowski, Sarah Elschenbroich, Kimmo Lehtimäki, Taneli Heikkinen, Larry Park, James Rosinski, Ladislav Mrzljak, Daniel Lavery, Anthony R West, Christopher J Schmidt, Margaret M Zaleska, Ignacio Munoz-Sanjuan
Huntington's disease (HD) symptoms are driven to a large extent by dysfunction of the basal ganglia circuitry. HD patients exhibit reduced striatal phoshodiesterase 10 (PDE10) levels. Using HD mouse models that exhibit reduced PDE10, we demonstrate the benefit of pharmacologic PDE10 inhibition to acutely correct basal ganglia circuitry deficits. PDE10 inhibition restored corticostriatal input and boosted cortically driven indirect pathway activity. Cyclic nucleotide signaling is impaired in HD models, and PDE10 loss may represent a homeostatic adaptation to maintain signaling...
November 25, 2016: Neuron
https://www.readbyqxmd.com/read/27916453/shank3-deficiency-impairs-heat-hyperalgesia-and-trpv1-signaling-in-primary-sensory-neurons
#2
Qingjian Han, Yong Ho Kim, Xiaoming Wang, Di Liu, Zhi-Jun Zhang, Alexandra L Bey, Mark Lay, Wonseok Chang, Temugin Berta, Yan Zhang, Yong-Hui Jiang, Ru-Rong Ji
Abnormal pain sensitivity is commonly associated with autism spectrum disorders (ASDs) and affects the life quality of ASD individuals. SHANK3 deficiency was implicated in ASD and pain dysregulation. Here, we report functional expression of SHANK3 in mouse dorsal root ganglion (DRG) sensory neurons and spinal cord presynaptic terminals. Homozygous and heterozygous Shank3 complete knockout (Δe4-22) results in impaired heat hyperalgesia in inflammatory and neuropathic pain. Specific deletion of Shank3 in Nav1...
November 24, 2016: Neuron
https://www.readbyqxmd.com/read/27916458/a-sensor-for-low-environmental-oxygen-in-the-mouse-main-olfactory-epithelium
#3
Katherin Bleymehl, Anabel Pérez-Gómez, Masayo Omura, Ana Moreno-Pérez, David Macías, Zhaodai Bai, Randall S Johnson, Trese Leinders-Zufall, Frank Zufall, Peter Mombaerts
Sensing the level of oxygen in the external and internal environments is essential for survival. Organisms have evolved multiple mechanisms to sense oxygen. No function in oxygen sensing has been attributed to any mammalian olfactory system. Here, we demonstrate that low environmental oxygen directly activates a subpopulation of sensory neurons in the mouse main olfactory epithelium. These neurons express the soluble guanylate cyclase Gucy1b2 and the cation channel Trpc2. Low oxygen induces calcium influx in these neurons, and Gucy1b2 and Trpc2 are required for these responses...
November 21, 2016: Neuron
https://www.readbyqxmd.com/read/27916457/molecular-basis-for-subtype-specificity-and-high-affinity-zinc-inhibition-in-the-glun1-glun2a-nmda-receptor-amino-terminal-domain
#4
Annabel Romero-Hernandez, Noriko Simorowski, Erkan Karakas, Hiro Furukawa
Zinc is vastly present in the mammalian brain and controls functions of various cell surface receptors to regulate neurotransmission. A distinctive characteristic of N-methyl-D-aspartate (NMDA) receptors containing a GluN2A subunit is that their ion channel activity is allosterically inhibited by a nano-molar concentration of zinc that binds to an extracellular domain called an amino-terminal domain (ATD). Despite physiological importance, the molecular mechanism underlying the high-affinity zinc inhibition has been incomplete because of the lack of a GluN2A ATD structure...
November 21, 2016: Neuron
https://www.readbyqxmd.com/read/27916456/acute-fasting-regulates-retrograde-synaptic-enhancement-through-a-4e-bp-dependent-mechanism
#5
Grant Kauwe, Kazuya Tsurudome, Jay Penney, Megumi Mori, Lindsay Gray, Mario R Calderon, Fatima Elazouzzi, Nicole Chicoine, Nahum Sonenberg, A Pejmun Haghighi
While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function at the Drosophila larval neuromuscular junction (NMJ). This negative regulation critically depends on transcriptional enhancement of eukaryotic initiation factor 4E binding protein (4E-BP) under the control of the transcription factor Forkhead box O (Foxo)...
November 21, 2016: Neuron
https://www.readbyqxmd.com/read/27889097/axonal-degeneration-is-regulated-by-a-transcriptional-program-that-coordinates-expression-of-pro-and-anti-degenerative-factors
#6
Maya Maor-Nof, Erez Romi, Hadas Sar Shalom, Valeria Ulisse, Calanit Raanan, Aviv Nof, Dena Leshkowitz, Roland Lang, Avraham Yaron
Developmental neuronal cell death and axonal elimination are controlled by transcriptional programs, of which their nature and the function of their components remain elusive. Here, we identified the dual specificity phosphatase Dusp16 as part of trophic deprivation-induced transcriptome in sensory neurons. Ablation of Dusp16 enhanced axonal degeneration in response to trophic withdrawal, suggesting that it has a protective function. Moreover, axonal skin innervation was severely reduced while neuronal elimination was increased in the Dusp16 knockout...
November 21, 2016: Neuron
https://www.readbyqxmd.com/read/27889096/novel-functional-properties-of-drosophila-cns-glutamate-receptors
#7
Yan Li, Poorva Dharkar, Tae-Hee Han, Mihaela Serpe, Chi-Hon Lee, Mark L Mayer
Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists...
November 21, 2016: Neuron
https://www.readbyqxmd.com/read/27916454/computational-precision-of-mental-inference-as-critical-source-of-human-choice-suboptimality
#8
Jan Drugowitsch, Valentin Wyart, Anne-Dominique Devauchelle, Etienne Koechlin
Making decisions in uncertain environments often requires combining multiple pieces of ambiguous information from external cues. In such conditions, human choices resemble optimal Bayesian inference, but typically show a large suboptimal variability whose origin remains poorly understood. In particular, this choice suboptimality might arise from imperfections in mental inference rather than in peripheral stages, such as sensory processing and response selection. Here, we dissociate these three sources of suboptimality in human choices based on combining multiple ambiguous cues...
November 16, 2016: Neuron
https://www.readbyqxmd.com/read/27866799/inhibitory-control-in-the-cortico-basal-ganglia-thalamocortical-loop-complex-regulation-and-interplay-with-memory-and-decision-processes
#9
Wei Wei, Xiao-Jing Wang
We developed a circuit model of spiking neurons that includes multiple pathways in the basal ganglia (BG) and is endowed with feedback mechanisms at three levels: cortical microcircuit, corticothalamic loop, and cortico-BG-thalamocortical system. We focused on executive control in a stop signal task, which is known to depend on BG across species. The model reproduces a range of experimental observations and shows that the newly discovered feedback projection from external globus pallidus to striatum is crucial for inhibitory control...
November 16, 2016: Neuron
https://www.readbyqxmd.com/read/27866798/long-distance-descending-spinal-neurons-ensure-quadrupedal-locomotor-stability
#10
Ludwig Ruder, Aya Takeoka, Silvia Arber
Locomotion is an essential animal behavior used for translocation. The spinal cord acts as key executing center, but how it coordinates many body parts located across distance remains poorly understood. Here we employed mouse genetic and viral approaches to reveal organizational principles of long-projecting spinal circuits and their role in quadrupedal locomotion. Using neurotransmitter identity, developmental origin, and projection patterns as criteria, we uncover that spinal segments controlling forelimbs and hindlimbs are bidirectionally connected by symmetrically organized direct synaptic pathways that encompass multiple genetically tractable neuronal subpopulations...
November 16, 2016: Neuron
https://www.readbyqxmd.com/read/27866800/neural-architecture-of-hunger-dependent-multisensory-decision-making-in-c-%C3%A2-elegans
#11
D Dipon Ghosh, Tom Sanders, Soonwook Hong, Li Yan McCurdy, Daniel L Chase, Netta Cohen, Michael R Koelle, Michael N Nitabach
Little is known about how animals integrate multiple sensory inputs in natural environments to balance avoidance of danger with approach to things of value. Furthermore, the mechanistic link between internal physiological state and threat-reward decision making remains poorly understood. Here we confronted C. elegans worms with the decision whether to cross a hyperosmotic barrier presenting the threat of desiccation to reach a source of food odor. We identified a specific interneuron that controls this decision via top-down extrasynaptic aminergic potentiation of the primary osmosensory neurons to increase their sensitivity to the barrier...
November 12, 2016: Neuron
https://www.readbyqxmd.com/read/27840000/coding-and-plasticity-in-the-mammalian-thermosensory-system
#12
David A Yarmolinsky, Yueqing Peng, Leah A Pogorzala, Michael Rutlin, Mark A Hoon, Charles S Zuker
Perception of the thermal environment begins with the activation of peripheral thermosensory neurons innervating the body surface. To understand how temperature is represented in vivo, we used genetically encoded calcium indicators to measure temperature-evoked responses in hundreds of neurons across the trigeminal ganglion. Our results show how warm, hot, and cold stimuli are represented by distinct population responses, uncover unique functional classes of thermosensory neurons mediating heat and cold sensing, and reveal the molecular logic for peripheral warmth sensing...
November 9, 2016: Neuron
https://www.readbyqxmd.com/read/27866797/the-impact-of-structural-heterogeneity-on-excitation-inhibition-balance-in-cortical-networks
#13
Itamar D Landau, Robert Egger, Vincent J Dercksen, Marcel Oberlaender, Haim Sompolinsky
Models of cortical dynamics often assume a homogeneous connectivity structure. However, we show that heterogeneous input connectivity can prevent the dynamic balance between excitation and inhibition, a hallmark of cortical dynamics, and yield unrealistically sparse and temporally regular firing. Anatomically based estimates of the connectivity of layer 4 (L4) rat barrel cortex and numerical simulations of this circuit indicate that the local network possesses substantial heterogeneity in input connectivity, sufficient to disrupt excitation-inhibition balance...
November 5, 2016: Neuron
https://www.readbyqxmd.com/read/27866796/interplay-between-hippocampal-sharp-wave-ripple-events-and-vicarious-trial-and-error-behaviors-in-decision-making
#14
Andrew E Papale, Mark C Zielinski, Loren M Frank, Shantanu P Jadhav, A David Redish
Current theories posit that memories encoded during experiences are subsequently consolidated into longer-term storage. Hippocampal sharp-wave-ripple (SWR) events have been linked to this consolidation process during sleep, but SWRs also occur during awake immobility, where their role remains unclear. We report that awake SWR rates at the reward site are inversely related to the prevalence of vicarious trial and error (VTE) behaviors, thought to be involved in deliberation processes. SWR rates were diminished immediately after VTE behaviors and an increase in the rate of SWR events at the reward site predicted a decrease in subsequent VTE behaviors at the choice point...
November 5, 2016: Neuron
https://www.readbyqxmd.com/read/27840001/actin-is-crucial-for-all-kinetically-distinguishable-forms-of-endocytosis-at-synapses
#15
Xin-Sheng Wu, Sung Hoon Lee, Jiansong Sheng, Zhen Zhang, Wei-Dong Zhao, Dongsheng Wang, Yinghui Jin, Patrick Charnay, James M Ervasti, Ling-Gang Wu
Mechanical force is needed to mediate endocytosis. Whether actin, the most abundant force-generating molecule, is essential for endocytosis is highly controversial in mammalian cells, particularly synapses, likely due to the use of actin blockers, the efficiency and specificity of which are often unclear in the studied cell. Here we addressed this issue using a knockout approach combined with measurements of membrane capacitance and fission pore conductance, imaging of vesicular protein endocytosis, and electron microscopy...
November 5, 2016: Neuron
https://www.readbyqxmd.com/read/27840002/hippocampal-offline-reactivation-consolidates-recently-formed-cell-assembly-patterns-during-sharp-wave-ripples
#16
Gido M van de Ven, Stéphanie Trouche, Colin G McNamara, Kevin Allen, David Dupret
The ability to reinstate neuronal assemblies representing mnemonic information is thought to require their consolidation through offline reactivation during sleep/rest. To test this, we detected cell assembly patterns formed by repeated neuronal co-activations in the mouse hippocampus during exploration of spatial environments. We found that the reinstatement of assembly patterns representing a novel, but not a familiar, environment correlated with their offline reactivation and was impaired by closed-loop optogenetic disruption of sharp wave-ripple oscillations...
November 4, 2016: Neuron
https://www.readbyqxmd.com/read/27839999/timing-rules-for-synaptic-plasticity-matched-to-behavioral-function
#17
Aparna Suvrathan, Hannah L Payne, Jennifer L Raymond
It is widely assumed that the complexity of neural circuits enables them to implement diverse learning tasks using just a few generic forms of synaptic plasticity. In contrast, we report that synaptic plasticity can itself be precisely tuned to the requirements of a learning task. We found that the rules for induction of long-term and single-trial plasticity at parallel fiber-to-Purkinje cell synapses vary across cerebellar regions. In the flocculus, associative plasticity in vitro and in vivo is narrowly tuned for an interval of ∼120 ms, which compensates for the specific processing delay for error signals to reach the flocculus during oculomotor learning...
November 4, 2016: Neuron
https://www.readbyqxmd.com/read/27839998/enzymatic-activity-of-the-scaffold-protein-rapsyn-for-synapse-formation
#18
Lei Li, Yu Cao, Haitao Wu, Xinchun Ye, Zhihui Zhu, Guanglin Xing, Chengyong Shen, Arnab Barik, Bin Zhang, Xiaoling Xie, Wenbo Zhi, Lin Gan, Huabo Su, Wen-Cheng Xiong, Lin Mei
Neurotransmission is ensured by a high concentration of neurotransmitter receptors at the postsynaptic membrane. This is mediated by scaffold proteins that bridge the receptors with cytoskeleton. One such protein is rapsyn (receptor-associated protein at synapse), which is essential for acetylcholine receptor (AChR) clustering and NMJ (neuromuscular junction) formation. We show that the RING domain of rapsyn contains E3 ligase activity. Mutation of the RING domain that abolishes the enzyme activity inhibits rapsyn- as well as agrin-induced AChR clustering in heterologous and muscle cells...
November 4, 2016: Neuron
https://www.readbyqxmd.com/read/27720486/a-designer-aav-variant-permits-efficient-retrograde-access-to-projection-neurons
#19
D Gowanlock R Tervo, Bum-Yeol Hwang, Sarada Viswanathan, Thomas Gaj, Maria Lavzin, Kimberly D Ritola, Sarah Lindo, Susan Michael, Elena Kuleshova, David Ojala, Cheng-Chiu Huang, Charles R Gerfen, Jackie Schiller, Joshua T Dudman, Adam W Hantman, Loren L Looger, David V Schaffer, Alla Y Karpova
Efficient retrograde access to projection neurons for the delivery of sensors and effectors constitutes an important and enabling capability for neural circuit dissection. Such an approach would also be useful for gene therapy, including the treatment of neurodegenerative disorders characterized by pathological spread through functionally connected and highly distributed networks. Viral vectors, in particular, are powerful gene delivery vehicles for the nervous system, but all available tools suffer from inefficient retrograde transport or limited clinical potential...
October 6, 2016: Neuron
https://www.readbyqxmd.com/read/27693257/reallocation-of-olfactory-cajal-retzius-cells-shapes-neocortex-architecture
#20
Cristina A de Frutos, Guy Bouvier, Yoko Arai, Morgane S Thion, Ludmilla Lokmane, Maryama Keita, Mario Garcia-Dominguez, Patrick Charnay, Tatsumi Hirata, Dieter Riethmacher, Elizabeth A Grove, Fadel Tissir, Mariano Casado, Alessandra Pierani, Sonia Garel
The neocortex undergoes extensive developmental growth, but how its architecture adapts to expansion remains largely unknown. Here, we investigated how early born Cajal-Retzius (CR) neurons, which regulate the assembly of cortical circuits, maintain a dense superficial distribution in the growing neocortex. We found that CR cell density is sustained by an activity-dependent importation of olfactory CR cells, which migrate into the neocortex after they have acted as axonal guidepost cells in the olfactory system...
September 28, 2016: Neuron
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