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Synaptic scaling

Ashwani Jha, Beate Diehl, Catherine Scott, Andrew W McEvoy, Parashkev Nachev
An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [1, 2]. That we are able to change our planned actions-a key criterion of volition [3]-so close to the time of their onset implies decision-making must reach deep into the execution of action itself [4-6]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [7], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [8-11]...
October 18, 2016: Current Biology: CB
Gordon X Wang, Stephen J Smith, Philippe Mourrain
The distribution of proteins within sub-synaptic compartments is an essential aspect of their neurological function. Current methodology such as electron microscopy (EM) and super-resolution imaging techniques can provide precise localization of proteins, but are often limited to a small number of one-time observations with narrow spatial and molecular coverage. The diversity of synaptic proteins and synapse types demands synapse analysis on a scale that is prohibitive with current methods. Here, we demonstrate SubSynMAP, a fast, multiplexed sub-synaptic protein analysis method using wide-field data from deconvolution array tomography (ATD)...
October 22, 2016: ELife
Christoph T Schanzenbächer, Sivakumar Sambandan, Julian D Langer, Erin M Schuman
Homeostatic scaling adjusts the strength of synaptic connections up or down in response to large changes in input. To identify the landscape of proteomic changes that contribute to opposing forms of homeostatic plasticity, we examined the plasticity-induced changes in the newly synthesized proteome. Cultured rat hippocampal neurons underwent homeostatic up-scaling or down-scaling. We used BONCAT (bio-orthogonal non-canonical amino acid tagging) to metabolically label, capture, and identify newly synthesized proteins, detecting and analyzing 5,940 newly synthesized proteins using mass spectrometry and label-free quantitation...
October 19, 2016: Neuron
Claire Guerrier, David Holcman
Binding of molecules, ions or proteins to small target sites is a generic step of cell activation. This process relies on rare stochastic events where a particle located in a large bulk has to find small and often hidden targets. We present here a hybrid discrete-continuum model that takes into account a stochastic regime governed by rare events and a continuous regime in the bulk. The rare discrete binding events are modeled by a Markov chain for the encounter of small targets by few Brownian particles, for which the arrival time is Poissonian...
October 18, 2016: Scientific Reports
Jérémie Barral, Alex D Reyes
The balance between excitation and inhibition (E-I balance) is maintained across brain regions though the network size, strength and number of synaptic connections, and connection architecture may vary substantially. We use a culture preparation to examine the homeostatic synaptic scaling rules that produce E-I balance and in vivo-like activity. We show that synaptic strength scales with the number of connections K as ∼ , close to the ideal theoretical value. Using optogenetic techniques, we delivered spatiotemporally patterned stimuli to neurons and confirmed key theoretical predictions: E-I balance is maintained, active decorrelation occurs and the spiking correlation increases with firing rate...
October 17, 2016: Nature Neuroscience
Pierre Wijdenes, Hasan Ali, Ryden Armstrong, Wali Zaidi, Colin Dalton, Naweed I Syed
Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with "nano-edges" that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes...
October 12, 2016: Scientific Reports
Nicola Strenzke, Rituparna Chakrabarti, Hanan Al-Moyed, Alexandra Müller, Gerhard Hoch, Tina Pangrsic, Gulnara Yamanbaeva, Christof Lenz, Kuan-Ting Pan, Elisabeth Auge, Ruth Geiss-Friedlander, Henning Urlaub, Nils Brose, Carolin Wichmann, Ellen Reisinger
The multi-C2 domain protein otoferlin is required for hearing and mutated in human deafness. Some OTOF mutations cause a mild elevation of auditory thresholds but strong impairment of speech perception. At elevated body temperature, hearing is lost. Mice homozygous for one of these mutations, Otof(I515T/I515T), exhibit a moderate hearing impairment involving enhanced adaptation to continuous or repetitive sound stimulation. In Otof(I515T/I515T) inner hair cells (IHCs), otoferlin levels are diminished by 65%, and synaptic vesicles are enlarged...
October 11, 2016: EMBO Journal
Moritz Armbruster, Elizabeth Hanson, Chris G Dulla
: Excitatory amino acid transporters (EAATs) are abundantly expressed by astrocytes, rapidly remove glutamate from the extracellular environment, and restrict the temporal and spatial extent of glutamate signaling. Studies probing EAAT function suggest that their capacity to remove glutamate is large and does not saturate, even with substantial glutamate challenges. In contrast, we report that neuronal activity rapidly and reversibly modulates EAAT-dependent glutamate transport. To date, no physiological manipulation has shown changes in functional glutamate uptake in a nonpathological state...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Marcus K Benna, Stefano Fusi
Memories are stored and retained through complex, coupled processes operating on multiple timescales. To understand the computational principles behind these intricate networks of interactions, we construct a broad class of synaptic models that efficiently harness biological complexity to preserve numerous memories by protecting them against the adverse effects of overwriting. The memory capacity scales almost linearly with the number of synapses, which is a substantial improvement over the square root scaling of previous models...
October 3, 2016: Nature Neuroscience
Nao Chuhma, Susana Mingote, Abigail Kalmbach, Leora Yetnikoff, Stephen Rayport
Brain imaging has revealed alterations in dopamine uptake, release, and receptor levels in patients with schizophrenia that have been resolved on the scale of striatal subregions. However, the underlying synaptic mechanisms are on a finer scale. Dopamine neuron synaptic actions vary across the striatum, involving variations not only in dopamine release but also in dopamine neuron connectivity, cotransmission, modulation, and activity. Optogenetic studies have revealed that dopamine neurons release dopamine in a synaptic signal mode, and that the neurons also release glutamate and gamma-aminobutyric acid as cotransmitters, with striking regional variation...
July 12, 2016: Biological Psychiatry
Tong Wang, Sally Martin, Tam H Nguyen, Callista B Harper, Rachel S Gormal, Ramon Martínez-Mármol, Shanker Karunanithi, Elizabeth J Coulson, Nick R Glass, Justin J Cooper-White, Bruno van Swinderen, Frédéric A Meunier
Axonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic signal. Here we show that upregulating synaptic activity markedly increased the flux of plasma membrane-derived retrograde endosomes (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured in microfluidic devices, and live Drosophila larval motor neurons...
2016: Nature Communications
Ekaterina Brocke, Upinder S Bhalla, Mikael Djurfeldt, Jeanette Hellgren Kotaleski, Michael Hanke
Multiscale modeling and simulations in neuroscience is gaining scientific attention due to its growing importance and unexplored capabilities. For instance, it can help to acquire better understanding of biological phenomena that have important features at multiple scales of time and space. This includes synaptic plasticity, memory formation and modulation, homeostasis. There are several ways to organize multiscale simulations depending on the scientific problem and the system to be modeled. One of the possibilities is to simulate different components of a multiscale system simultaneously and exchange data when required...
2016: Frontiers in Computational Neuroscience
Rinaldo David D'Souza, Andrew Max Meier, Pawan Bista, Quanxin Wang, Andreas Burkhalter
Diverse features of sensory stimuli are selectively processed in distinct brain areas. The relative recruitment of inhibitory and excitatory neurons within an area controls the gain of neurons for appropriate stimulus coding. We examined how such a balance of inhibition and excitation is differentially recruited across multiple levels of a cortical hierarchy by mapping the locations and strengths of synaptic inputs to pyramidal and parvalbumin (PV)-expressing neurons in feedforward and feedback pathways interconnecting primary (V1) and two higher visual areas...
September 26, 2016: ELife
Shujia Zhu, Eric Gouaux
Ionotropic glutamate receptors (iGluRs) transduce signals derived from release of the excitatory neurotransmitter glutamate from pre-synaptic neurons into excitation of post-synaptic neurons on a millisecond time-scale. In recent years, the elucidation of full-length iGluR structures of NMDA, AMPA and kainate receptors by X-ray crystallography and single particle cryo-electron microscopy has greatly enhanced our understanding of the interrelationships between receptor architecture and gating mechanism. Here we briefly review full-length iGluR structures and discuss the similarities and differences between NMDA receptors and non-NMDA iGluRs...
September 20, 2016: Neuropharmacology
Saeed Haghiri, Arash Ahmadi, Mehrdad Saif
Glial cells, also known as neuroglia or glia, are non-neuronal cells providing support and protection for neurons in the central nervous system (CNS). They also act as supportive cells in the brain. Among a variety of glial cells, the star-shaped glial cells, i.e., astrocytes, are the largest cell population in the brain. The important role of astrocyte such as neuronal synchronization, synaptic information regulation, feedback to neural activity and extracellular regulation make the astrocytes play a vital role in brain disease...
September 20, 2016: IEEE Transactions on Biomedical Circuits and Systems
Robin Spiess, Richard George, Matthew Cook, Peter U Diehl
Despite an abundance of computational models for learning of synaptic weights, there has been relatively little research on structural plasticity, i.e., the creation and elimination of synapses. Especially, it is not clear how structural plasticity works in concert with spike-timing-dependent plasticity (STDP) and what advantages their combination offers. Here we present a fairly large-scale functional model that uses leaky integrate-and-fire neurons, STDP, homeostasis, recurrent connections, and structural plasticity to learn the input encoding, the relation between inputs, and to infer missing inputs...
2016: Frontiers in Computational Neuroscience
Jason E Pipkin, Eric A Bushong, Mark H Ellisman, William B Kristan
Microscale connectomics involves the large-scale acquisition of high-resolution serial electron micrographs from which neuronal arbors can be reconstructed and synapses can be detected. In addition to connectivity information, these data sets are also rich with structural information, including vesicle types, number of postsynaptic partners at a given presynaptic site, and spatial distribution of synaptic inputs and outputs. This study uses serial block-face scanning electron microscopy (EM) to collect two volumes of serial EM data from ganglia of the medicinal leech...
December 15, 2016: Journal of Comparative Neurology
Karthik H Shankar, Inder Singh, Marc W Howard
Predicting the timing and order of future events is an essential feature of cognition in higher life forms. We propose a neural mechanism to nondestructively translate the current state of spatiotemporal memory into the future, so as to construct an ordered set of future predictions almost instantaneously. We hypothesize that within each cycle of hippocampal theta oscillations, the memory state is swept through a range of translations to yield an ordered set of future predictions through modulations in synaptic connections...
September 14, 2016: Neural Computation
A Rigal, S Mouchabac, C S Peretti
INTRODUCTION: The number of patients with depression in the world is 350 millions according to estimates. The search for new treatments, particularly in forms of resistant depression, is necessary given the growing number of patients experiencing treatment failure and resistance. Scopolamine, an anticholinergic antimuscarinic molecule, is one of the treatments under evaluation. It falls within the assumptions of cholinergic disruption of the pathophysiology of depression, at different levels (genetic, receptorial [muscarinic and glutamate receptors], hormonal, synaptic…)...
September 9, 2016: L'Encéphale
Michael Shoykhet, Jason W Middleton
Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window...
2016: Frontiers in Neural Circuits
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