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Synaptic scaling

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https://www.readbyqxmd.com/read/29786079/dissection-of-dna-double-strand-break-repair-using-novel-single-molecule-forceps
#1
Jing L Wang, Camille Duboc, Qian Wu, Takashi Ochi, Shikang Liang, Susan E Tsutakawa, Susan P Lees-Miller, Marc Nadal, John A Tainer, Tom L Blundell, Terence R Strick
Repairing DNA double-strand breaks (DSBs) by nonhomologous end joining (NHEJ) requires multiple proteins to recognize and bind DNA ends, process them for compatibility, and ligate them together. We constructed novel DNA substrates for single-molecule nanomanipulation, allowing us to mechanically detect, probe, and rupture in real-time DSB synapsis by specific human NHEJ components. DNA-PKcs and Ku allow DNA end synapsis on the 100 ms timescale, and the addition of PAXX extends this lifetime to ~2 s. Further addition of XRCC4, XLF and ligase IV results in minute-scale synapsis and leads to robust repair of both strands of the nanomanipulated DNA...
May 21, 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29783994/large-scale-transcriptomic-analysis-reveals-that-pridopidine-reverses-aberrant-gene-expression-and-activates-neuroprotective-pathways-in-the-yac128-hd-mouse
#2
Rebecca Kusko, Jennifer Dreymann, Jermaine Ross, Yoonjeong Cha, Renan Escalante-Chong, Marta Garcia-Miralles, Liang Juin Tan, Michael E Burczynski, Ben Zeskind, Daphna Laifenfeld, Mahmoud Pouladi, Michal Geva, Iris Grossman, Michael R Hayden
BACKGROUND: Huntington Disease (HD) is an incurable autosomal dominant neurodegenerative disorder driven by an expansion repeat giving rise to the mutant huntingtin protein (mHtt), which is known to disrupt a multitude of transcriptional pathways. Pridopidine, a small molecule in development for treatment of HD, has been shown to improve motor symptoms in HD patients. In HD animal models, pridopidine exerts neuroprotective effects and improves behavioral and motor functions. Pridopidine binds primarily to the sigma-1 receptor, (IC50 ~ 100 nM), which mediates its neuroprotective properties, such as rescue of spine density and aberrant calcium signaling in HD neuronal cultures...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29771335/loss-of-fragile-x-protein-fmrp-impairs-homeostatic-synaptic-downscaling-through-tumor-suppressor-p53-and-ubiquitin-e3-ligase-nedd4-2
#3
Kwan Young Lee, Kathryn A Jewett, Hee Jung Chung, Nien-Pei Tsai
Synaptic scaling allows neurons to homeostatically readjust synaptic strength upon chronic neural activity perturbations. Although altered synaptic scaling has been implicated to underlie imbalanced brain excitability in neurological disorders such as autism spectrum disorders and epilepsy, the molecular dysregulation and restoration of synaptic scaling in those diseases have not been demonstrated. Here, we showed that the homeostatic synaptic downscaling is absent in the hippocampal neurons of Fmr1 KO mice, the mouse model of the most common inherited autism, Fragile X Syndrome (FXS)...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29765480/effect-of-spike-timing-dependent-plasticity-on-stochastic-burst-synchronization-in-a-scale-free-neuronal-network
#4
Sang-Yoon Kim, Woochang Lim
We consider an excitatory population of subthreshold Izhikevich neurons which cannot fire spontaneously without noise. As the coupling strength passes a threshold, individual neurons exhibit noise-induced burstings. This neuronal population has adaptive dynamic synaptic strengths governed by the spike-timing-dependent plasticity (STDP). However, STDP was not considered in previous works on stochastic burst synchronization (SBS) between noise-induced burstings of sub-threshold neurons. Here, we study the effect of additive STDP on SBS by varying the noise intensity D in the Barabási-Albert scale-free network (SFN)...
June 2018: Cognitive Neurodynamics
https://www.readbyqxmd.com/read/29760525/two-distinct-mechanisms-for-experience-dependent-homeostasis
#5
Michelle C D Bridi, Roberto de Pasquale, Crystal L Lantz, Yu Gu, Andrew Borrell, Se-Young Choi, Kaiwen He, Trinh Tran, Su Z Hong, Andrew Dykman, Hey-Kyoung Lee, Elizabeth M Quinlan, Alfredo Kirkwood
Models of firing rate homeostasis such as synaptic scaling and the sliding synaptic plasticity modification threshold predict that decreasing neuronal activity (for example, by sensory deprivation) will enhance synaptic function. Manipulations of cortical activity during two forms of visual deprivation, dark exposure (DE) and binocular lid suture, revealed that, contrary to expectations, spontaneous firing in conjunction with loss of visual input is necessary to lower the threshold for Hebbian plasticity and increase miniature excitatory postsynaptic current (mEPSC) amplitude...
May 14, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29758721/diffusion-advection-within-dynamic-biological-gaps-driven-by-structural-motion
#6
Robert J Asaro, Qiang Zhu, Kuanpo Lin
To study the significance of advection in the transport of solutes, or particles, within thin biological gaps (channels), we examine theoretically the process driven by stochastic fluid flow caused by random thermal structural motion, and we compare it with transport via diffusion. The model geometry chosen resembles the synaptic cleft; this choice is motivated by the cleft's readily modeled structure, which allows for well-defined mechanical and physical features that control the advection process. Our analysis defines a Péclet-like number, A^{D}, that quantifies the ratio of time scales of advection versus diffusion...
April 2018: Physical Review. E
https://www.readbyqxmd.com/read/29752691/analytical-modelling-of-temperature-effects-on-an-ampa-type-synapse
#7
Dominik S Kufel, Grzegorz M Wojcik
It was previously reported, that temperature may significantly influence neural dynamics on the different levels of brain function. Thus, in computational neuroscience, it would be useful to make models scalable for a wide range of various brain temperatures. However, lack of experimental data and an absence of temperature-dependent analytical models of synaptic conductance does not allow to include temperature effects at the multi-neuron modeling level. In this paper, we propose a first step to deal with this problem: A new analytical model of AMPA-type synaptic conductance, which is able to incorporate temperature effects in low-frequency stimulations...
May 11, 2018: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/29751506/neurocognitive-disorders-and-dehydration-in-older-patients-clinical-experience-supports-the-hydromolecular-hypothesis-of-dementia
#8
Michele Lauriola, Antonio Mangiacotti, Grazia D'Onofrio, Leandro Cascavilla, Francesco Paris, Giulia Paroni, Davide Seripa, Antonio Greco, Daniele Sancarlo
Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS)...
May 3, 2018: Nutrients
https://www.readbyqxmd.com/read/29748610/distinct-homeostatic-modulations-stabilize-reduced-postsynaptic-receptivity-in-response-to-presynaptic-dlk-signaling
#9
Pragya Goel, Dion Dickman
Synapses are constructed with the stability to last a lifetime, yet sufficiently flexible to adapt during injury. Although fundamental pathways that mediate intrinsic responses to neuronal injury have been defined, less is known about how synaptic partners adapt. We have investigated responses in the postsynaptic cell to presynaptic activation of the injury-related Dual Leucine Zipper Kinase pathway at the Drosophila neuromuscular junction. We find that the postsynaptic compartment reduces neurotransmitter receptor levels, thus depressing synaptic strength...
May 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/29744390/stage-1-registered-report-variation-in-neurodevelopmental-outcomes-in-children-with-sex-chromosome-trisomies-protocol-for-a-test-of-the-double-hit-hypothesis
#10
Dianne F Newbury, Nuala H Simpson, Paul A Thompson, Dorothy V M Bishop
Background : The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. Group averages, however, obscure a wide range of outcomes. Hypothesis: The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. Neuroligin-4 genes are expressed from X and Y chromosomes; they play an important role in synaptic development and have been implicated in neurodevelopment...
2018: Wellcome Open Research
https://www.readbyqxmd.com/read/29739869/synaptic-release-of-acetylcholine-rapidly-suppresses-cortical-activity-by-recruiting-muscarinic-receptors-in-layer-4
#11
Rajan Dasgupta, Frederik Seibt, Michael Beierlein
Cholinergic afferents from the basal forebrain (BF) can influence cortical activity on rapid time scales, enabling sensory information processing and exploratory behavior. However, our understanding of how synaptically released acetylcholine (ACh) influences cellular targets in distinct cortical layers remains incomplete. Previous studies have shown that rapid changes in cortical dynamics induced by phasic BF activity can be mediated by the activation of nicotinic ACh receptors (nAChRs) expressed in distinct types of GABAergic interneurons...
May 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29735711/ultrafast-glutamate-sensors-resolve-high-frequency-release-at-schaffer-collateral-synapses
#12
Nordine Helassa, Céline D Dürst, Catherine Coates, Silke Kerruth, Urwa Arif, Christian Schulze, J Simon Wiegert, Michael Geeves, Thomas G Oertner, Katalin Török
Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGlu f ) and ultrafast (iGlu u ) variants with comparable brightness but increased K d for glutamate (137 μM and 600 μM, respectively)...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29730043/identifying-the-genetic-risk-factors-for-treatment-response-to-lurasidone-by-genome-wide-association-study-a-meta-analysis-of-samples-from-three-independent-clinical-trials
#13
Jiang Li, Antony Loebel, Herbert Y Meltzer
A genome-wide association study (GWAS) of response of schizophrenia patients to the atypical antipsychotic drug, lurasidone, based on two double-blind registration trials, identified SNPs from four classes of genes as predictors of efficacy, but none were genome wide significant (GWS). After inclusion of data from a third lurasidone trial, meta-analysis identified a GWS marker and other findings consistent with our first study. The primary end-point was change in Total Positive and Negative Syndrome Scale (PANSS) between baseline and last observation carried forward...
May 2, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29728449/schaffer-collateral-inputs-to-ca1-excitatory-and-inhibitory-neurons-follow-different-connectivity-rules
#14
Osung Kwon, Linqing Feng, Shaul Druckmann, Jinhyun Kim
Neural circuits, governed by a complex interplay between excitatory and inhibitory neurons, are the substrate for information processing, and the organization of synaptic connectivity in neural network is an important determinant of circuit function. Here, we analyzed the fine structure of connectivity in hippocampal CA1 excitatory and inhibitory neurons innervated by Schaffer collaterals (SCs) using mGRASP in male mice. Our previous study revealed spatially structured synaptic connectivity between CA3-CA1 pyramidal cells (PCs)...
May 4, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29719243/active-zone-scaffold-protein-ratios-tune-functional-diversity-across-brain-synapses
#15
Andreas Fulterer, Till F M Andlauer, Anatoli Ender, Marta Maglione, Katherine Eyring, Jennifer Woitkuhn, Martin Lehmann, Tanja Matkovic-Rachid, Joerg R P Geiger, Alexander M Walter, Katherine I Nagel, Stephan J Sigrist
High-throughput electron microscopy has started to reveal synaptic connectivity maps of single circuits and whole brain regions, for example, in the Drosophila olfactory system. However, efficacy, timing, and frequency tuning of synaptic vesicle release are also highly diversified across brain synapses. These features critically depend on the nanometer-scale coupling distance between voltage-gated Ca2+ channels (VGCCs) and the synaptic vesicle release machinery. Combining light super resolution microscopy with in vivo electrophysiology, we show here that two orthogonal scaffold proteins (ELKS family Bruchpilot, BRP, and Syd-1) cluster-specific (M)Unc13 release factor isoforms either close (BRP/Unc13A) or further away (Syd-1/Unc13B) from VGCCs across synapses of the Drosophila olfactory system, resulting in different synapse-characteristic forms of short-term plasticity...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29703767/encephalitis-with-mglur5-antibodies-symptoms-and-antibody-effects
#16
Marianna Spatola, Lidia Sabater, Jesús Planagumà, Eugenia Martínez-Hernandez, Thaís Armangué, Harald Prüss, Takahiro Iizuka, Ruben L Caparó Oblitas, Jean-Christophe Antoine, Richard Li, Nicholas Heaney, Niall Tubridy, Elvira Munteis Olivas, Myrna R Rosenfeld, Francesc Graus, Josep Dalmau
OBJECTIVE: To report the clinical features of 11 patients with metabotropic glutamate receptor 5 (mGluR5) antibody-associated encephalitis, immunoglobulin G (IgG) subclass, and effects of the antibodies on neuronal mGluR5 clusters. METHODS: Clinical information was retrospectively obtained from referring physicians. Antibodies to mGluR5 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays. The effects of the antibodies were examined on rat hippocampal neurons with reported techniques...
April 27, 2018: Neurology
https://www.readbyqxmd.com/read/29700661/parkinson-disease-from-mendelian-forms-to-genetic-susceptibility-new-molecular-insights-into-the-neurodegeneration-process
#17
REVIEW
Amin Karimi-Moghadam, Saeid Charsouei, Benjamin Bell, Mohammad Reza Jabalameli
Parkinson disease (PD) is known as a common progressive neurodegenerative disease which is clinically diagnosed by the manifestation of numerous motor and nonmotor symptoms. PD is a genetically heterogeneous disorder with both familial and sporadic forms. To date, researches in the field of Parkinsonism have identified 23 genes or loci linked to rare monogenic familial forms of PD with Mendelian inheritance. Biochemical studies revealed that the products of these genes usually play key roles in the proper protein and mitochondrial quality control processes, as well as synaptic transmission and vesicular recycling pathways within neurons...
April 26, 2018: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29698767/regulation-of-neural-differentiation-synaptic-scaling-and-animal-behavior-by-mecp2-phophorylation
#18
Xiaofen Zhong, Hongda Li, Jason Kim, Qiang Chang
Highly expressed in the mammalian brain and widely distributed across the genome, MeCP2 is a key player in recognizing modified DNA and interpreting the epigenetic information encoded in different DNA methylation/hydroxymethylation patterns. Alterations in sequence or copy number of the X-linked human MECP2 gene cause either Rett syndrome (RTT) or MECP2 duplication syndrome. Alterations in MECP2 levels have also been identified in patients with autism. To fully understand the significant role of MECP2 in regulating the development and function of the nervous system, it is important to study all aspects of MeCP2 function...
April 23, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29696604/genomic-and-imaging-biomarkers-in-schizophrenia
#19
J T Reddaway, J L Doherty, T Lancaster, D Linden, J T Walters, J Hall
Recent large-scale genomic studies have confirmed that schizophrenia is a polygenic syndrome and have implicated a number of biological pathways in its aetiology. Both common variants individually of small effect and rarer but more penetrant genetic variants have been shown to play a role in the pathogenesis of the disorder. No simple Mendelian forms of the condition have been identified, but progress has been made in stratifying risk on the basis of the polygenic burden of common variants individually of small effect, and the contribution of rarer variants of larger effect such as Copy Number Variants (CNVs)...
April 26, 2018: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/29686261/synaptic-nanomodules-underlie-the-organization-and-plasticity-of-spine-synapses
#20
Martin Hruska, Nathan Henderson, Sylvain J Le Marchand, Haani Jafri, Matthew B Dalva
Experience results in long-lasting changes in dendritic spine size, yet how the molecular architecture of the synapse responds to plasticity remains poorly understood. Here a combined approach of multicolor stimulated emission depletion microscopy (STED) and confocal imaging in rat and mouse demonstrates that structural plasticity is linked to the addition of unitary synaptic nanomodules to spines. Spine synapses in vivo and in vitro contain discrete and aligned subdiffraction modules of pre- and postsynaptic proteins whose number scales linearly with spine size...
May 2018: Nature Neuroscience
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