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https://www.readbyqxmd.com/read/29346769/switching-on-depression-and-potentiation-in-the-cerebellum
#1
Andrew R Gallimore, Taegon Kim, Keiko Tanaka-Yamamoto, Erik De Schutter
Long-term depression (LTD) and long-term potentiation (LTP) in the cerebellum are important for motor learning. However, the signaling mechanisms controlling whether LTD or LTP is induced in response to synaptic stimulation remain obscure. Using a unified model of LTD and LTP at the cerebellar parallel fiber-Purkinje cell (PF-PC) synapse, we delineate the coordinated pre- and postsynaptic signaling that determines the direction of plasticity. We show that LTP is the default response to PF stimulation above a well-defined frequency threshold...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346758/size-dependent-axonal-bouton-dynamics-following-visual-deprivation-in%C3%A2-vivo
#2
Rosanna P Sammons, Claudia Clopath, Samuel J Barnes
Persistent synapses are thought to underpin the storage of sensory experience, yet little is known about their structural plasticity in vivo. We investigated how persistent presynaptic structures respond to the loss of primary sensory input. Using in vivo two-photon (2P) imaging, we measured fluctuations in the size of excitatory axonal boutons in L2/3 of adult mouse visual cortex after monocular enucleation. The average size of boutons did not change after deprivation, but the range of bouton sizes was reduced...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346754/input-specific-nmdar-dependent-potentiation-of-dendritic-gabaergic-inhibition
#3
Chiayu Q Chiu, James S Martenson, Maya Yamazaki, Rie Natsume, Kenji Sakimura, Susumu Tomita, Steven J Tavalin, Michael J Higley
Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29346364/mutations-in-caenorhabditis-elegans-neuroligin-like-glit-1-the-apoptosis-pathway-and-the-calcium-chaperone-crt-1-increase-dopaminergic-neurodegeneration-after-6-ohda-treatment
#4
Sarah-Lena Offenburger, Elisabeth Jongsma, Anton Gartner
The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the aetiology of which is associated with increased levels of oxidative stress. We used C. elegans to screen for genes that protect dopaminergic neurons against oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like) homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), an oxidative-stress inducing drug that is specifically taken up into dopaminergic neurons...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29343769/ckamp44-modulates-integration-of-visual-inputs-in-the-lateral-geniculate-nucleus
#5
Xufeng Chen, Muhammad Aslam, Tim Gollisch, Kevin Allen, Jakob von Engelhardt
Relay neurons in the dorsal lateral geniculate nucleus (dLGN) receive excitatory inputs from retinal ganglion cells (RGCs). Retinogeniculate synapses are characterized by a prominent short-term depression of AMPA receptor (AMPAR)-mediated currents, but the underlying mechanisms and its function for visual integration are not known. Here we identify CKAMP44 as a crucial auxiliary subunit of AMPARs in dLGN relay neurons, where it increases AMPAR-mediated current amplitudes and modulates gating of AMPARs. Importantly, CKAMP44 is responsible for the distinctive short-term depression in retinogeniculate synapses by reducing the rate of recovery from desensitization of AMPARs...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343640/single-cell-transcriptomics-of-the-developing-lateral-geniculate-nucleus-reveals-insights-into-circuit-assembly-and-refinement
#6
Brian T Kalish, Lucas Cheadle, Sinisa Hrvatin, M Aurel Nagy, Samuel Rivera, Megan Crow, Jesse Gillis, Rory Kirchner, Michael E Greenberg
Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29342395/indistinguishable-synapses-lead-to-sparse-networks
#7
Joseph Snider
Neurons integrate information from many neighbors when they process information. Inputs to a given neuron are thus indistinguishable from one another. Under the assumption that neurons maximize their information storage, indistinguishability is shown to place a strong constraint on the distribution of strengths between neurons. The distribution of individual synapse strengths is found to follow a modified Boltzmann distribution with strength proportional to [Formula: see text]. The model is shown to be consistent with experimental data from Caenorhabditis elegans connectivity and in vivo synaptic strength measurements...
January 17, 2018: Neural Computation
https://www.readbyqxmd.com/read/29342202/cells-containing-aragonite-crystals-mediate-responses-to-gravity-in-trichoplax-adhaerens-placozoa-an-animal-lacking-neurons-and-synapses
#8
Tatiana D Mayorova, Carolyn L Smith, Katherine Hammar, Christine A Winters, Natalia B Pivovarova, Maria A Aronova, Richard D Leapman, Thomas S Reese
Trichoplax adhaerens has only six cell types. The function as well as the structure of crystal cells, the least numerous cell type, presented an enigma. Crystal cells are arrayed around the perimeter of the animal and each contains a birefringent crystal. Crystal cells resemble lithocytes in other animals so we looked for evidence they are gravity sensors. Confocal microscopy showed that their cup-shaped nuclei are oriented toward the edge of the animal, and that the crystal shifts downward under the influence of gravity...
2018: PloS One
https://www.readbyqxmd.com/read/29342141/monitoring-t-cell-dendritic-cell-interactions-in-vivo-by-intercellular-enzymatic-labelling
#9
Giulia Pasqual, Aleksey Chudnovskiy, Jeroen M J Tas, Marianna Agudelo, Lawrence D Schweitzer, Ang Cui, Nir Hacohen, Gabriel D Victora
Interactions between different cell types are essential for multiple biological processes, including immunity, embryonic development and neuronal signalling. Although the dynamics of cell-cell interactions can be monitored in vivo by intravital microscopy, this approach does not provide any information on the receptors and ligands involved or enable the isolation of interacting cells for downstream analysis. Here we describe a complementary approach that uses bacterial sortase A-mediated cell labelling across synapses of immune cells to identify receptor-ligand interactions between cells in living mice, by generating a signal that can subsequently be detected ex vivo by flow cytometry...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342042/long-term-administration-of-salicylate-induced-changes-in-bdnf-expression-and-creb-phosphorylation-in-the-auditory-cortex-of-rats
#10
Bin Yi, Cong Wu, Runjie Shi, Kun Han, Haibin Sheng, Bei Li, Ling Mei, Xueling Wang, Zhiwu Huang, Hao Wu
HYPOTHESIS: We investigated whether salicylate induces tinnitus through alteration of the expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC). BACKGROUND: Salicylate medication is frequently used for long-term treatment in clinical settings, but it may cause reversible tinnitus. Salicylate-induced tinnitus is associated with changes related to central auditory neuroplasticity...
January 16, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29340224/camkii-is-involved-in-the-choline-induced-downregulation-of-acetylcholine-release-in-mouse-motor-synapses
#11
A E Gaydukov, O P Balezina
We investigated the involvement of calcium-dependent enzymes, protein kinase C (PKC) and calcium-calmodulin-dependent protein kinase II (CaMKII), in the signaling pathway triggered by the activation of presynaptic alpha7-type nicotinic acetylcholine receptors by exogenous choline, leading to downregulation of the evoked acetylcholine (ACh) release in mouse motor synapses. Blockade of PKC with chelerythrine neither changed the evoked release of ACh by itself nor prevented the inhibitory effect of choline. The CaMKII blocker KN-62 did not affect synaptic activity but fully prevented the choline-induced downregulation of ACh release...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29339550/relative-target-affinities-of-t-cell-dependent-bispecific-antibodies-determine-biodistribution-in-a-solid-tumor-mouse-model
#12
Danielle Mandikian, Nene Takahashi, Amy A Lo, Ji Li, Jeffrey Eastham-Anderson, Dionysos Slaga, Jason Ho, Maria Hristopoulos, Robyn Clark, Klara Totpal, Kedan Lin, Sean B Joseph, Mark S Dennis, Saileta Prabhu, Teemu T Junttila, C Andrew Boswell
Anti-HER2/CD3, a T cell-dependent bispecific antibody (TDB) construct, induces T cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic synapse. TDB design is a very challenging process that requires consideration of multiple parameters. While therapeutic antibody design strategy is commonly driven by striving for the highest attainable antigen binding affinity, little is known about how the affinity of each TDB arm can affect the targeting ability of the other arm and the consequent distribution and efficacy...
January 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29339486/cell-type-specific-role-for-nucleus-accumbens-neuroligin-2-in-depression-and-stress-susceptibility
#13
Mitra Heshmati, Hossein Aleyasin, Caroline Menard, Daniel J Christoffel, Meghan E Flanigan, Madeline L Pfau, Georgia E Hodes, Ashley E Lepack, Lucy K Bicks, Aki Takahashi, Ramesh Chandra, Gustavo Turecki, Mary Kay Lobo, Ian Maze, Sam A Golden, Scott J Russo
Behavioral coping strategies are critical for active resilience to stress and depression; here we describe a role for neuroligin-2 (NLGN-2) in the nucleus accumbens (NAc). Neuroligins (NLGN) are a family of neuronal postsynaptic cell adhesion proteins that are constituents of the excitatory and inhibitory synapse. Importantly, NLGN-3 and NLGN-4 mutations are strongly implicated as candidates underlying the development of neuropsychiatric disorders with social disturbances such as autism, but the role of NLGN-2 in neuropsychiatric disease states is unclear...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338873/opioid-and-psychostimulant-plasticity-targeting-overlap-in-nucleus-accumbens-glutamate-signaling
#14
REVIEW
Matthew Hearing, Nicholas Graziane, Yan Dong, Mark J Thomas
Commonalities in addictive behavior, such as craving, stimuli-driven drug seeking, and a high propensity for relapse following abstinence, have pushed for a unified theory of addiction that encompasses most abused substances. This unitary theory has recently been challenged - citing distinctions in structural neural plasticity, biochemical signaling, and neural circuitry to argue that addiction to opioids and psychostimulants is behaviorally and neurobiologically distinct. Recent more selective examination of drug-induced plasticity has highlighted that these two drug classes promote an overall reward circuitry signaling overlap through modifying excitatory synapses in the nucleus accumbens - a key constituent of the reward system...
January 12, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29338087/thrombospondin-4-acts-on-pre-synaptic-calcium-channel-alpha-2-delta-1-subunit-to-induce-synaptogenesis-between-sensory-and-spinal-cord-neurons-through-a-t-type-calcium-channel-dependent-pathway-that-is-blocked-by-early-low-dose-gabapentin-treatments
#15
Yanhui Peter Yu, Nian Gong, Tae Dong Kweon, Benjamin Vo, Z David Luo
BACKGROUND AND PURPOSE: Nerve injury induces concurrent upregulation of calcium channel alpha-2-delta-1 subunit (Cav α2 δ1 ) and extracellular matrix protein thrombospondin-4 (TSP4) in dorsal root ganglia and dorsal spinal cord, leading to neuropathic pain state development. Interactions of these proteins promote aberrant excitatory synaptogenesis that contributes to neuropathic pain state development through unknown mechanisms. We investigated the contributory role of Cav α2 δ1 /TSP4 to synaptogenesis, and pathway involved in vitro, and whether gabapentin could block this process and pain development in vivo...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29337691/the-neutral-sphingomyelinase-2-in-t-cell-receptor-signaling-and-polarity
#16
Lena Collenburg, Sibylle Schneider-Schaulies, Elita Avota
Hydrolyzing its substrate sphingomyelin at the cytosolic leaflet of cellular membranes, the neutral sphingomyelinase 2 (NSM2) generates microdomains which serve as docking sites for signaling proteins and thereby, functions to regulate signal relay. This has been particularly studied in cellular stress responses while the regulatory role of this enzyme in the immune cell compartment has only recently emerged. In T cells, phenotypic polarization by co-ordinated cytoskeletal remodeling is central to motility and interaction with endothelial or antigenpresenting cells during tissue recruitment or immune synapse formation, respectively...
June 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29336496/donepezil-reverses-dendritic-spine-morphology-adaptations-and-fmr1-epigenetic-modifications-in-hippocampus-of-adult-rats-after-adolescent-alcohol-exposure
#17
Patrick J Mulholland, Tara L Teppen, Kelsey M Miller, Hannah G Sexton, Subhash C Pandey, H Scott Swartzwelder
BACKGROUND: Adolescent intermittent ethanol (AIE) exposure produces persistent impairments in cholinergic and epigenetic signaling and alters markers of synapses in the hippocampal formation, effects that are thought to drive hippocampal dysfunction in adult rodents. Donepezil (Aricept), a cholinesterase inhibitor, is used clinically to ameliorate memory-related cognitive deficits. Given that donepezil also prevents morphological impairment in preclinical models of neuropsychiatric disorders, we investigated the ability of donepezil to reverse morphological and epigenetic adaptations in the hippocampus of adult rats exposed to AIE...
January 16, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29335913/analyzing-the-interactions-of-mrnas-mirnas-lncrnas-and-circrnas-to-predict-competing-endogenous-rna-networks-in-glioblastoma
#18
Yang Yuan, Li Jiaoming, Wang Xiang, Liu Yanhui, Jiang Shu, Gou Maling, Mao Qing
Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs...
January 15, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29335431/synaptic-localisation-of-srf-coactivators-mkl1-and-mkl2-and-their-role-in-dendritic-spine-morphology
#19
Marisa Kaneda, Hiroyuki Sakagami, Yamato Hida, Toshihisa Ohtsuka, Natsumi Satou, Yuta Ishibashi, Mamoru Fukuchi, Anna Krysiak, Mitsuru Ishikawa, Daisuke Ihara, Katarzyna Kalita, Akiko Tabuchi
The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF) coactivators, which are highly expressed in the brain. Accordingly, MKL plays important roles in dendritic morphology, neuronal migration, and brain development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are found in patients with schizophrenia and autism spectrum disorder, respectively. Thus, studies on the precise synaptic localisation and function of MKL in neurons are warranted. In this study, we generated and tested new antibodies that specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29335016/autophagy-is-required-for-human-umbilical-cord-mesenchymal-stem-cells-to-improve-spatial-working-memory-in-app-ps1-transgenic-mouse-model
#20
Wen Li, Kai Li, Jing Gao, Zhuo Yang
BACKGROUND: Recent studies have shown that autophagy plays a central role in mesenchymal stem cells (MSCs), and many studies have shown that human umbilical cord MSCs (huMSCs) can treat Alzheimer's disease (AD) through a variety of mechanisms. However, no studies have looked at the effects of autophagy on neuroprotective function of huMSCs in the AD mouse model. Thus, in this study we investigated whether inhibition of autophagy could weaken or block the function of huMSCs through in vitro and in vivo experiments...
January 15, 2018: Stem Cell Research & Therapy
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