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Neuron

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https://www.readbyqxmd.com/read/28318784/kinetics-of-endogenous-camkii-required-for-synaptic-plasticity-revealed-by-optogenetic-kinase-inhibitor
#1
Hideji Murakoshi, Myung Eun Shin, Paula Parra-Bueno, Erzsebet M Szatmari, Akihiro C E Shibata, Ryohei Yasuda
Elucidating temporal windows of signaling activity required for synaptic and behavioral plasticity is crucial for understanding molecular mechanisms underlying these phenomena. Here, we developed photoactivatable autocamtide inhibitory peptide 2 (paAIP2), a genetically encoded, light-inducible inhibitor of CaMKII activity. The photoactivation of paAIP2 in neurons for 1-2 min during the induction of LTP and structural LTP (sLTP) of dendritic spines inhibited these forms of plasticity in hippocampal slices of rodents...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28285824/clasp2-links-reelin-to-the-cytoskeleton-during-neocortical-development
#2
Gregory M Dillon, William A Tyler, Kerilyn C Omuro, John Kambouris, Camila Tyminski, Shawna Henry, Tarik F Haydar, Uwe Beffert, Angela Ho
The Reelin signaling pathway plays a crucial role in regulating neocortical development. However, little is known about how Reelin controls the cytoskeleton during neuronal migration. Here, we identify CLASP2 as a key cytoskeletal effector in the Reelin signaling pathway. We demonstrate that CLASP2 has distinct roles during neocortical development regulating neuron production and controlling neuron migration, polarity, and morphogenesis. We found downregulation of CLASP2 in migrating neurons leads to mislocalized cells in deeper cortical layers, abnormal positioning of the centrosome-Golgi complex, and aberrant length/orientation of the leading process...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28285823/input-specific-plasticity-and-homeostasis-at-the-drosophila-larval-neuromuscular-junction
#3
Zachary L Newman, Adam Hoagland, Krishan Aghi, Kurtresha Worden, Sabrina L Levy, Jun Ho Son, Luke P Lee, Ehud Y Isacoff
Synaptic connections undergo activity-dependent plasticity during development and learning, as well as homeostatic re-adjustment to ensure stability. Little is known about the relationship between these processes, particularly in vivo. We addressed this with novel quantal resolution imaging of transmission during locomotive behavior at glutamatergic synapses of the Drosophila larval neuromuscular junction. We find that two motor input types, Ib and Is, provide distinct forms of excitatory drive during crawling and differ in key transmission properties...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28285822/astrocytes-control-circadian-timekeeping-in-the-suprachiasmatic-nucleus-via-glutamatergic-signaling
#4
Marco Brancaccio, Andrew P Patton, Johanna E Chesham, Elizabeth S Maywood, Michael H Hastings
The suprachiasmatic nucleus (SCN) of the hypothalamus orchestrates daily rhythms of physiology and behavior in mammals. Its circadian (∼24 hr) oscillations of gene expression and electrical activity are generated intrinsically and can persist indefinitely in temporal isolation. This robust and resilient timekeeping is generally regarded as a product of the intrinsic connectivity of its neurons. Here we show that neurons constitute only one "half" of the SCN clock, the one metabolically active during circadian daytime...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28285821/grasp1-regulates-synaptic-plasticity-and-learning-through-endosomal-recycling-of-ampa-receptors
#5
Shu-Ling Chiu, Graham Hugh Diering, Bing Ye, Kogo Takamiya, Chih-Ming Chen, Yuwu Jiang, Tejasvi Niranjan, Charles E Schwartz, Tao Wang, Richard L Huganir
Learning depends on experience-dependent modification of synaptic efficacy and neuronal connectivity in the brain. We provide direct evidence for physiological roles of the recycling endosome protein GRASP1 in glutamatergic synapse function and animal behavior. Mice lacking GRASP1 showed abnormal excitatory synapse number, synaptic plasticity, and hippocampal-dependent learning and memory due to a failure in learning-induced synaptic AMPAR incorporation. We identified two GRASP1 point mutations from intellectual disability (ID) patients that showed convergent disruptive effects on AMPAR recycling and glutamate uncaging-induced structural and functional plasticity...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28285820/dynamic-nigrostriatal-dopamine-biases-action-selection
#6
Christopher D Howard, Hao Li, Claire E Geddes, Xin Jin
Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn't reflect reward prediction error, timing, or value as single factors alone...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28285819/imaging-erk-and-pka-activation-in-single-dendritic-spines-during-structural-plasticity
#7
Shen Tang, Ryohei Yasuda
Extracellular signal-regulated kinase (ERK) and protein kinase A (PKA) play important roles in LTP and spine structural plasticity. While fluorescence resonance energy transfer (FRET)-based sensors for these kinases had previously been developed, they did not provide sufficient sensitivity for imaging small neuronal compartments, such as single dendritic spines in brain slices. Here we improved the sensitivity of FRET-based kinase sensors for monitoring kinase activity under two-photon fluorescence lifetime imaging microscopy (2pFLIM)...
March 6, 2017: Neuron
https://www.readbyqxmd.com/read/28262416/the-auxiliary-calcium-channel-subunit-%C3%AE-2%C3%AE-4-is-required-for-axonal-elaboration-synaptic-transmission-and-wiring-of-rod-photoreceptors
#8
Yuchen Wang, Katherine E Fehlhaber, Ignacio Sarria, Yan Cao, Norianne T Ingram, Debbie Guerrero-Given, Ben Throesch, Kristin Baldwin, Naomi Kamasawa, Toshihisa Ohtsuka, Alapakkam P Sampath, Kirill A Martemyanov
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca(2+) channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with CaV1...
February 23, 2017: Neuron
https://www.readbyqxmd.com/read/28238550/diverse-non-genetic-allele-specific-expression-effects-shape-genetic-architecture-at-the-cellular-level-in-the-mammalian-brain
#9
Wei-Chao Huang, Elliott Ferris, Tong Cheng, Cornelia Stacher Hörndli, Kelly Gleason, Carol Tamminga, Janice D Wagner, Kenneth M Boucher, Jan L Christian, Christopher Gregg
Interactions between genetic and epigenetic effects shape brain function, behavior, and the risk for mental illness. Random X inactivation and genomic imprinting are epigenetic allelic effects that are well known to influence genetic architecture and disease risk. Less is known about the nature, prevalence, and conservation of other potential epigenetic allelic effects in vivo in the mouse and primate brain. Here we devise genomics, in situ hybridization, and mouse genetics strategies to uncover diverse allelic effects in the brain that are not caused by imprinting or genetic variation...
February 23, 2017: Neuron
https://www.readbyqxmd.com/read/28238548/context-and-output-layer-dependent-long-term-ensemble-plasticity-in-a-sensory-circuit
#10
Yoshiyuki Yamada, Khaleel Bhaukaurally, Tamás J Madarász, Alexandre Pouget, Ivan Rodriguez, Alan Carleton
Sensory information is translated into ensemble representations by various populations of projection neurons in brain circuits. The dynamics of ensemble representations formed by distinct channels of output neurons in diverse behavioral contexts remains largely unknown. We studied the two output neuron layers in the olfactory bulb (OB), mitral and tufted cells, using chronic two-photon calcium imaging in awake mice. Both output populations displayed similar odor response profiles. During passive sensory experience, both populations showed reorganization of ensemble odor representations yet stable pattern separation across days...
February 23, 2017: Neuron
https://www.readbyqxmd.com/read/28262417/cell-autonomous-excitation-of-midbrain-dopamine-neurons-by-endocannabinoid-dependent-lipid-signaling
#11
Stephanie C Gantz, Bruce P Bean
The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing...
February 21, 2017: Neuron
https://www.readbyqxmd.com/read/28238549/population-coding-in-an-innately-relevant-olfactory-area
#12
Giuliano Iurilli, Sandeep Robert Datta
Different olfactory cortical regions are thought to harbor distinct sensory representations, enabling each area to play a unique role in odor perception and behavior. In the piriform cortex (PCx), spatially dispersed sensory inputs evoke activity in distributed ensembles of neurons that act as substrates for odor learning. In contrast, the posterolateral cortical amygdala (plCoA) receives hardwired inputs that may link specific odor cues to innate olfactory behaviors. Here we show that despite stark differences in the patterning of plCoA and PCx inputs, odor-evoked neural ensembles in both areas are equally capable of discriminating odors, and exhibit similar odor tuning, reliability, and correlation structure...
February 18, 2017: Neuron
https://www.readbyqxmd.com/read/28238546/regulation-of-thalamic-and-cortical-network-synchrony-by-scn8a
#13
Christopher D Makinson, Brian S Tanaka, Jordan M Sorokin, Jennifer C Wong, Catherine A Christian, Alan L Goldin, Andrew Escayg, John R Huguenard
Voltage-gated sodium channel (VGSC) mutations cause severe epilepsies marked by intermittent, pathological hypersynchronous brain states. Here we present two mechanisms that help to explain how mutations in one VGSC gene, Scn8a, contribute to two distinct seizure phenotypes: (1) hypoexcitation of cortical circuits leading to convulsive seizure resistance, and (2) hyperexcitation of thalamocortical circuits leading to non-convulsive absence epilepsy. We found that loss of Scn8a leads to altered RT cell intrinsic excitability and a failure in recurrent RT synaptic inhibition...
February 18, 2017: Neuron
https://www.readbyqxmd.com/read/28238551/molecular-mechanism-of-ampa-receptor-modulation-by-tarp-stargazin
#14
Anat Ben-Yaacov, Moshe Gillor, Tomer Haham, Alon Parsai, Mohammad Qneibi, Yael Stern-Bach
AMPA receptors (AMPARs) mediate the majority of fast excitatory transmission in the brain and critically contribute to synaptic plasticity and pathology. AMPAR trafficking and gating are tightly controlled by auxiliary transmembrane AMPAR regulatory proteins (TARPs). Here, using systematic domain swaps with the TARP-insensitive kainate receptor GluK2, we show that AMPAR interaction with the prototypical TARP stargazin/γ2 primarily involves the AMPAR membrane domains M1 and M4 of neighboring subunits, initiated or stabilized by the AMPAR C-tail, and that these interactions are sufficient to enable full receptor modulation...
February 17, 2017: Neuron
https://www.readbyqxmd.com/read/28215558/optimal-degrees-of-synaptic-connectivity
#15
Ashok Litwin-Kumar, Kameron Decker Harris, Richard Axel, Haim Sompolinsky, L F Abbott
Synaptic connectivity varies widely across neuronal types. Cerebellar granule cells receive five orders of magnitude fewer inputs than the Purkinje cells they innervate, and cerebellum-like circuits, including the insect mushroom body, also exhibit large divergences in connectivity. In contrast, the number of inputs per neuron in cerebral cortex is more uniform and large. We investigate how the dimension of a representation formed by a population of neurons depends on how many inputs each neuron receives and what this implies for learning associations...
February 16, 2017: Neuron
https://www.readbyqxmd.com/read/28238547/hallmarks-of-alzheimer-s-disease-in-stem-cell-derived-human-neurons-transplanted-into-mouse-brain
#16
Ira Espuny-Camacho, Amaia M Arranz, Mark Fiers, An Snellinx, Kunie Ando, Sebastian Munck, Jerome Bonnefont, Laurie Lambot, Nikky Corthout, Lorna Omodho, Elke Vanden Eynden, Enrico Radaelli, Ina Tesseur, Selina Wray, Andreas Ebneth, John Hardy, Karelle Leroy, Jean-Pierre Brion, Pierre Vanderhaeghen, Bart De Strooper
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration...
February 15, 2017: Neuron
https://www.readbyqxmd.com/read/28215557/long-term-two-photon-imaging-in-awake-macaque-monkey
#17
Ming Li, Fang Liu, Hongfei Jiang, Tai Sing Lee, Shiming Tang
Successful application of two-photon imaging with genetic tools in awake macaque monkeys will enable fundamental advances in our understanding of higher cognitive function at the level of molecular and neuronal circuits. Here we report techniques for long-term two-photon imaging in awake macaque monkeys. Using genetically encoded indicators including GCaMP5 and GCaMP6s delivered by AAV2/1 into the visual cortex, we demonstrate that high-quality two-photon imaging of large neuronal populations can be achieved and maintained in awake monkeys for months...
February 8, 2017: Neuron
https://www.readbyqxmd.com/read/28279363/synaptic-vesicle-clusters-at-synapses-a-distinct-liquid-phase
#18
REVIEW
Dragomir Milovanovic, Pietro De Camilli
Phase separation in the cytoplasm is emerging as a major principle in intracellular organization. In this process, sets of macromolecules assemble themselves into liquid compartments that are distinct from the surrounding medium but are not delimited by membrane boundaries. Here, we discuss how phase separation, in which a component of one of the two phases is vesicles rather than macromolecules, could underlie the formation of synaptic vesicle (SV) clusters in proximity to presynaptic sites. The organization of SVs into a liquid phase could explain how SVs remain tightly clustered without being stably bound to a scaffold so that they can be efficiently recruited to release site by active zone components...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28279362/labeled-as-innate-but-not-innately-labeled
#19
Yoram Ben-Shaul
In this issue of Neuron, Iurilli and Datta (2017) conduct a comprehensive analysis of odor responses in the posterolateral cortical amygdala, a brain region implicated in innate processing of olfactory cues. Unexpectedly, neuronal responses in this region do not reveal preferred representations of stimulus valence.
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28279361/tarps-and-ampa-receptors-function-follows-form
#20
James E Huettner
In this issue of Neuron, Ben-Yaacov et al. (2017) dissect the interaction between AMPA receptors and auxiliary (TARP) subunits, revealing essential roles for the receptor transmembrane and cytoplasmic domains, as well as for the TARP extracellular EX2 loop.
March 8, 2017: Neuron
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