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https://www.readbyqxmd.com/read/29222951/neuronal-pas-domain-protein-4-npas4-controls-neuronal-homeostasis-in-pentylenetetrazole-induced-epilepsy-through-the-induction-of-homer1a
#1
Wei Shan, Taku Nagai, Motoki Tanaka, Norimichi Itoh, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Masahiro Sokabe, Kiyofumi Yamada
Neuronal intrinsic homeostatic scaling-down of excitatory synapse has been implicated in epilepsy pathogenesis to prevent the neuronal circuits from hyper-excitability. Recent findings suggest a role for neuronal PAS domain protein 4 (Npas4), an activity-dependent neuron-specific transcription factor in epileptogenesis, however, the underlying mechanism by which Npas4 regulates epilepsy remains unclear. We herein propose that limbic seizure activity up-regulates Npas4-homer1a signaling in the hippocampus, thereby contributing to epileptogenesis in mice...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29222785/neuronal-cell-morphology-in-primary-cerebellar-granule-cells-using-high-content-analysis
#2
Nicholas Radio, Steven Frank
Neurite outgrowth, one of the underlying cellular processes that defines the development and functionality of the mammalian nervous system, is also a sensitive indicator of neuronal cell health. From screening libraries of putative neurotherapeutic compounds to analyzing the millions of environmental pollutants for which we have inadequate neurotoxicity safety data, the large volume of chemical compounds that require evaluation is a major obstacle for manual imaging and analysis methods. In this context, high-content analysis (HCA) has emerged as a sensitive and accurate method for detecting changes in neuronal cell morphology within a format applicable to screening large chemical libraries...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222783/culture-of-mouse-giant-central-nervous-system-synapses-and-application-for-imaging-and-electrophysiological-analyses
#3
Dimitar Dimitrov, Laurent Guillaud, Kohgaku Eguchi, Tomoyuki Takahashi
Primary neuronal cell culture preparations are widely used to investigate synaptic functions. This chapter describes a detailed protocol for the preparation of a neuronal cell culture in which giant calyx-type synaptic terminals are formed. This chapter also presents detailed protocols for utilizing the main technical advantages provided by such a preparation, namely, labeling and imaging of synaptic organelles and electrophysiological recordings directly from presynaptic terminals.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222130/stargazin-and-cornichon-3-relieve-polyamine-block-of-ampa-receptors-by-enhancing-blocker-permeation
#4
Patricia M G E Brown, Hugo McGuire, Derek Bowie
Most ligand- and voltage-gated ion channels assemble as signaling complexes consisting of pore-forming and auxiliary subunits. In the mammalian brain, AMPA-type ionotropic glutamate receptors (AMPARs) coassemble with several families of auxiliary subunits that regulate channel gating as well as ion channel block and permeation. Previous work has shown that auxiliary proteins stargazin (or γ2) and cornichon-3 (CNIH-3) attenuate the cytoplasmic polyamine channel block of AMPARs, although the underlying mechanism has yet to be established...
December 8, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29221909/maintaining-the-active-zone-demand-supply-and-disposal-of-core-active-zone-proteins
#5
REVIEW
Noam E Ziv
Chemical synapses are sites of cell-cell contact specialized for transmission of signals between neurons and their respective targets. Neurotransmission occurs through the secretion of neurotransmitters at specialized presynaptic membrane regions known as Active Zones (AZs). AZ composition and function are now characterized quite well. Much less is known, however, on the manners by which these unique specializations are maintained for weeks, months, and presumably years. Here we focus on core AZ components that make up the Cytoskeleton associated with the AZ (CAZ) - their lifetimes, their supply and their disposal...
December 5, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29221908/how-to-maintain-active-zone-integrity-during-high-frequency-transmission
#6
REVIEW
Niklas Byczkowicz, Andreas Ritzau-Jost, Igor Delvendahl, Stefan Hallermann
In the central nervous system, the frequency at which reliable synaptic transmission can be maintained varies strongly between different types of synapses. Several pre- and postsynaptic processes must interact to enable high-frequency synaptic transmission. One of the mechanistically most challenging issues arises during repetitive neurotransmitter release, when synaptic vesicles fuse in rapid sequence with the presynaptic plasma membrane within the active zone (AZ), potentially interfering with the structural integrity of the AZ itself...
December 5, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29221907/coupling-of-exocytosis-and-endocytosis-at-the-presynaptic-active-zone
#7
REVIEW
Tanja Maritzen, Volker Haucke
Brain function depends on the ability of neurons to communicate with each other via the regulated exocytosis of neurotransmitter-containing synaptic vesicles (SVs) at specialized presynaptic release sites termed active zones (AZs). The presynaptic AZ comprises an assembly of large multidomain proteins that link the machinery for vesicle fusion to sites of voltage-dependent Ca2+ entry. Following SV fusion at AZ release sites SV membranes are retrieved by compensatory endocytosis, and SVs are reformed. Recent data suggest that Ca2+-triggered SV exocytosis at AZs and endocytic retrieval of SVs may be functionally and physically linked...
December 5, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29221161/piriform-cortical-glutamatergic-and-gabaergic-neurons-express-coordinated-plasticity-for-whisker-induced-odor-recall
#8
Yahui Liu, Zilong Gao, Changfeng Chen, Bo Wen, Li Huang, Rongjing Ge, Shidi Zhao, Ruichen Fan, Jing Feng, Wei Lu, Liping Wang, Jin-Hui Wang
Neural plasticity occurs in learning and memory. Coordinated plasticity at glutamatergic and GABAergic neurons during memory formation remains elusive, which we investigate in a mouse model of associative learning by cellular imaging and electrophysiology. Paired odor and whisker stimulations lead to whisker-induced olfaction response. In mice that express this cross-modal memory, the neurons in the piriform cortex are recruited to encode newly acquired whisker signal alongside innate odor signal, and their response patterns to these associated signals are different...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220673/de-novo-variants-in-gria4-lead-to-intellectual-disability-with-or-without-seizures-and-gait-abnormalities
#9
Sonja Martin, Adam Chamberlin, Deepali N Shinde, Maja Hempel, Tim M Strom, Allison Schreiber, Jessika Johannsen, Lilian Bomme Ousager, Martin J Larsen, Lars Kjaersgaard Hansen, Ali Fatemi, Julie S Cohen, Johannes Lemke, Kristina P Sørensen, Katherine L Helbig, Davor Lessel, Rami Abou Jamra
Using trio whole-exome sequencing, we have identified de novo heterozygous pathogenic variants in GRIA4 in five unrelated individuals with intellectual disability and other symptoms. GRIA4 encodes an AMPA receptor subunit known as GluR4, which is found on excitatory glutamatergic synapses and is important for learning and memory. Four of the variants are located in the highly conserved SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra-cellular domain. Molecular modeling of the altered protein showed that three of the variants in the SYTANLAAF motif orient toward the center of the pore region and most likely lead to disturbance of the gating mechanism...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29220306/improving-spiking-dynamical-networks-accurate-delays-higher-order-synapses-and-time-cells
#10
Aaron R Voelker, Chris Eliasmith
Researchers building spiking neural networks face the challenge of improving the biological plausibility of their model networks while maintaining the ability to quantitatively characterize network behavior. In this work, we extend the theory behind the neural engineering framework (NEF), a method of building spiking dynamical networks, to permit the use of a broad class of synapse models while maintaining prescribed dynamics up to a given order. This theory improves our understanding of how low-level synaptic properties alter the accuracy of high-level computations in spiking dynamical networks...
December 8, 2017: Neural Computation
https://www.readbyqxmd.com/read/29220305/spiking-neural-classifier-with-lumped-dendritic-nonlinearity-and-binary-synapses-a-current-mode-vlsi-implementation-and-analysis
#11
Aritra Bhaduri, Amitava Banerjee, Subhrajit Roy, Sougata Kar, Arindam Basu
We present a neuromorphic current mode implementation of a spiking neural classifier with lumped square law dendritic nonlinearity. It has been shown previously in software simulations that such a system with binary synapses can be trained with structural plasticity algorithms to achieve comparable classification accuracy with fewer synaptic resources than conventional algorithms. We show that even in real analog systems with manufacturing imperfections (CV of 23.5% and 14.4% for dendritic branch gains and leaks respectively), this network is able to produce comparable results with fewer synaptic resources...
December 8, 2017: Neural Computation
https://www.readbyqxmd.com/read/29218993/energy-landscape-of-the-substrate-translocation-equilibrium-of-plasma-membrane-glutamate-transporters
#12
Jiali Wang, Thomas Albers, Christof T Grewer
Glutamate transporters maintain a large glutamate concentration gradient across synaptic membranes and are, thus, critical for functioning of the excitatory synapse. Mammalian glutamate transporters concentrate glutamate inside cells through energetic coupling of glutamate flux to the transmembrane concentration gradient of Na+. Structural models based on an archeal homologue of mammalian glutamate transporters, GltPh, suggest an elevator-like carrier mechanism. However, the energetic determinants of this carrier-based movement are not well understood...
December 8, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29218821/activity-dependent-control-of-nmda-receptor-subunit-composition-at-hippocampal-mossy-fibre-synapses
#13
Mario Carta, Bettadapura N Srikumar, Adam Gorlewicz, Nelson Rebola, Christophe Mulle
Single neurons express NMDARs with distinct subunit composition and biophysical properties which can be segregated in an input-specific manner. The dynamic control of the heterogeneous distribution of synaptic NMDARs is crucial to control input-dependent synaptic integration and plasticity. In hippocampal CA3 pyramidal cells (CA3 PCs) from mice of both sexes, we found that mossy fibre (Mf) synapses display a markedly lower proportion of GluN2B containing NMDARs than associative/commissural synapses. The mechanism involved in such heterogeneous distribution of GluN2B subunits is not known...
December 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29218745/expression-of-the-potassium-chloride-co-transporter-kcc2-within-the-avian-song-system
#14
Christopher E Vaaga, Kimberly E Miller, Agnes L Bodor, David J Perkel
Songbirds learn to produce vocalizations early in life by listening to, then copying the songs of conspecific males. The anterior forebrain pathway, homologous to a basal ganglia-forebrain circuit, is essential for song learning. The projection between the striato-pallidal structure, Area X, and the medial portion of the dorsolateral thalamic nucleus (DLM) is strongly hyperpolarizing in adults, due to a very negative chloride reversal potential (Person and Perkel, 2005). The chloride reversal potential is determined, in part, by the expression level of a neuron-specific potassium-chloride cotransporter, KCC2, which is developmentally upregulated in mammals...
December 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29218324/intellicount-high-throughput-quantification-of-fluorescent-synaptic-protein-puncta-by-machine-learning
#15
J A Fantuzzo, V R Mirabella, A H Hamod, R P Hart, J D Zahn, Z P Pang
Synapse formation analyses can be performed by imaging and quantifying fluorescent signals of synaptic markers. Traditionally, these analyses are done using simple or multiple thresholding and segmentation approaches or by labor-intensive manual analysis by a human observer. Here, we describe Intellicount, a high-throughput, fully-automated synapse quantification program which applies a novel machine learning (ML)-based image processing algorithm to systematically improve region of interest (ROI) identification over simple thresholding techniques...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29218323/sap97-binding-partner-cript-promotes-dendrite-growth-in-vitro-and-in-vivo
#16
Lei Zhang, Angela Marie Jablonski, Jelena Mojsilovic-Petrovic, Hua Ding, Steven Seeholzer, Ian Paterson Newton, Inke Nathke, Rachael Neve, JinBin Zhai, Yuan Shang, Mingjie Zhang, Robert Gordon Kalb
The dendritic tree is a key determinant of neuronal information processing. In the motor system, the dendritic tree of spinal cord neurons undergoes dramatic remodeling in an activity-dependent manner during early postnatal life. This leads to the proper segmental spinal cord connectivity that subserves normal locomotor behavior. One molecular system driving the establishment of dendrite architecture of mammalian motor neurons relies on AMPA receptors (AMPA-Rs) assembled with the GluA1 subunit, and this occurs in an NMDA receptor (NMDA-R)-independent manner...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29218002/xenopus-laevis-as-a-model-organism-for-the-study-of-spinal-cord-formation-development-function-and-regeneration
#17
REVIEW
Laura N Borodinsky
The spinal cord is the first central nervous system structure to develop during vertebrate embryogenesis, underscoring its importance to the organism. Because of its early formation, accessibility to the developing spinal cord in amniotes is challenging, often invasive and the experimental approaches amenable to model systems like mammals are limited. In contrast, amphibians, in general and the African-clawed frog Xenopus laevis, in particular, offer model systems in which the formation of the spinal cord, the differentiation of spinal neurons and glia and the establishment of spinal neuron and neuromuscular synapses can be easily investigated with minimal perturbations to the whole organism...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/29218000/synapse-specific-regulation-revealed-at-single-synapses-is-concealed-when-recording-multiple-synapses
#18
Justin Lines, Ana Covelo, Ricardo Gómez, Lan Liu, Alfonso Araque
Synaptic transmission and its activity-dependent modulation, known as synaptic plasticity, are fundamental processes in nervous system function. Neurons may receive thousands of synaptic contacts, but synaptic regulation may occur only at individual or discrete subsets of synapses, which may have important consequences on the spatial extension of the modulation of synaptic information. Moreover, while several electrophysiological methods are used to assess synaptic transmission at different levels of observation, i...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29217824/soluble-tau-has-devastating-effects-on-the-structural-plasticity-of-hippocampal-granule-neurons
#19
M Bolós, N Pallas-Bazarra, J Terreros-Roncal, J R Perea, J Jurado-Arjona, J Ávila, M Llorens-Martín
Tau is a neuronal microtubule-associated protein with countless physiological functions. Although the detrimental effects of insoluble aggregated Tau have been widely studied, recent evidence supports the notion that soluble Tau (composed mostly of monomers and dimers) is also toxic for neurons. Here we evaluated the long-term impact of a single stereotaxic injection of human soluble Tau on hippocampal granule neurons in mice. At the ultrastructural level, soluble Tau reduced the number of afferent synapses and caused a dramatic depletion of synaptic vesicles both in afferent and efferent synapses...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29217683/insulin-like-growth-factor-ii-targets-the-mtor-pathway-to-reverse-autism-like-phenotypes-in-mice
#20
Adam B Steinmetz, Sarah A Stern, Amy S Kohtz, Giannina Descalzi, Cristina M Alberini
Autism spectrum disorder (ASD) is a developmental disability characterized by impairments in social interaction and repetitive behavior, and is also associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASD symptomatology; thus, identifying novel therapies is urgently needed. We used male BTBR T+Itpr3tf /J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of ASD, to test the effects of systemic administration of insulin like growth factor II (IGF-II), a polypeptide that crosses the blood brain barrier and acts as a cognitive enhancer...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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