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https://www.readbyqxmd.com/read/29054881/ablation-of-tfr1-in-purkinje-cells-inhibits-mglu1-trafficking-and-impairs-motor-coordination-but-not-autistic-like-behaviors
#1
Jia-Huan Zhou, Xin-Tai Wang, Liang Zhou, Lin Zhou, Fang-Xiao Xu, Li-Da Su, Hao Wang, Fan Jia, Fu-Qiang Xu, Gui-Quan Chen, Chris De Zeeuw, Ying Shen
Group 1 metabotropic glutamate receptors (mGlu1/5) are critical to synapse formation and participate in synaptic long-term potentiation (LTP) and long-term depression (LTD) in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a trans-membrane protein of clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29054336/network-design-and-the-brain
#2
REVIEW
Saket Navlakha, Ziv Bar-Joseph, Alison L Barth
Neural circuits have evolved to accommodate similar information processing challenges as those faced by engineered systems. Here, we compare neural versus engineering strategies for constructing networks. During circuit development, synapses are overproduced and then pruned back over time, whereas in engineered networks, connections are initially sparse and are then added over time. We provide a computational perspective on these two different approaches, including discussion of how and why they are used, insights that one can provide the other, and areas for future joint investigation...
October 17, 2017: Trends in Cognitive Sciences
https://www.readbyqxmd.com/read/29054293/corticostriatal-plasticity-neuronal-ensembles-and-regulation-of-drug-seeking-behavior
#3
Ana-Clara Bobadilla, Jasper A Heinsbroek, Cassandra D Gipson, William C Griffin, Christie D Fowler, Paul J Kenny, Peter W Kalivas
The idea that interconnected neuronal ensembles code for specific behaviors has been around for decades; however, recent technical improvements allow studying these networks and their causal role in initiating and maintaining behavior. In particular, the role of ensembles in drug-seeking behaviors in the context of addiction is being actively investigated. Concurrent with breakthroughs in quantifying ensembles, research has identified a role for synaptic glutamate spillover during relapse. In particular, the transient relapse-associated changes in glutamatergic synapses on accumbens neurons, as well as in adjacent astroglia and extracellular matrix, are key elements of the synaptic plasticity encoded by drug use and the metaplasticity induced by drug-associated cues that precipitate drug-seeking behaviors...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/29054039/control-of-brain-energy-supply-by-astrocytes
#4
REVIEW
Ross Nortley, David Attwell
Astrocytes form an anatomical bridge between the vasculature and neuronal synapses. Recent work suggests that they play a key role in regulating brain energy supply by increasing blood flow to regions where neurons are active, and setting the baseline level of blood flow. Controversy persists over whether lactate derived from astrocyte glycolysis is used to power oxidative phosphorylation in neurons, but astrocytes sustain neuronal ATP production by recycling neurotransmitter glutamate that would otherwise need to be resynthesised from glucose, and by providing a short-term energy store in the form of glycogen that can be mobilised when neurons are active...
October 17, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29054036/snava-a-real-time-multi-fpga-multi-model-spiking-neural-network-simulation-architecture
#5
Athul Sripad, Giovanny Sanchez, Mireya Zapata, Vito Pirrone, Taho Dorta, Salvatore Cambria, Albert Marti, Karthikeyan Krishnamourthy, Jordi Madrenas
Spiking Neural Networks (SNN) for Versatile Applications (SNAVA) simulation platform is a scalable and programmable parallel architecture that supports real-time, large-scale, multi-model SNN computation. This parallel architecture is implemented in modern Field-Programmable Gate Arrays (FPGAs) devices to provide high performance execution and flexibility to support large-scale SNN models. Flexibility is defined in terms of programmability, which allows easy synapse and neuron implementation. This has been achieved by using a special-purpose Processing Elements (PEs) for computing SNNs, and analyzing and customizing the instruction set according to the processing needs to achieve maximum performance with minimum resources...
October 5, 2017: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/29053799/erythropoietin-induces-homeostatic-plasticity-at-hippocampal-synapses
#6
Raquel B Dias, Tiago M Rodrigues, Diogo M Rombo, Filipa F Ribeiro, Joana Rodrigues, Jennifer McGarvey, Catarina Orcinha, Jeremy M Henley, Ana M Sebastião
The cytokine erythropoietin (EPO) is the master regulator of erythropoiesis. Intriguingly, many studies have shown that the cognitive performance of patients receiving EPO for its hematopoietic effects is enhanced, which prompted the growing interest in the use of EPO-based strategies to treat neuropsychiatric disorders. EPO plays key roles in brain development and maturation, but also modulates synaptic transmission. However, the mechanisms underlying the latter have remained elusive. Here, we show that acute (40-60 min) exposure to EPO presynaptically downregulates spontaneous and afferent-evoked excitatory transmission, without affecting basal firing of action potentials...
July 5, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29053699/evaluation-of-synapse-density-in-hippocampal-rodent-brain-slices
#7
Faye McLeod, Aude Marzo, Marina Podpolny, Soledad Galli, Patricia Salinas
In the brain, synapses are specialized junctions between neurons, determining the strength and spread of neuronal signaling. The number of synapses is tightly regulated during development and neuronal maturation. Importantly, deficits in synapse number can lead to cognitive dysfunction. Therefore, the evaluation of synapse number is an integral part of neurobiology. However, as synapses are small and highly compact in the intact brain, the assessment of absolute number is challenging. This protocol describes a method to easily identify and evaluate synapses in hippocampal rodent slices using immunofluorescence microscopy...
October 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29051550/studying-the-role-of-axon-fasciculation-during-development-in-a-computational-model-of-the-xenopus-tadpole-spinal-cord
#8
Oliver Davis, Robert Merrison-Hort, Stephen R Soffe, Roman Borisyuk
During nervous system development growing axons can interact with each other, for example by adhering together in order to produce bundles (fasciculation). How does such axon-axon interaction affect the resulting axonal trajectories, and what are the possible benefits of this process in terms of network function? In this paper we study these questions by adapting an existing computational model of the development of neurons in the Xenopus tadpole spinal cord to include interactions between axons. We demonstrate that even relatively weak attraction causes bundles to appear, while if axons weakly repulse each other their trajectories diverge such that they fill the available space...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051391/trace-eyeblink-conditioning-is-associated-with-changes-in-synaptophysin-immunoreactivity-in-the-cerebellar-interpositus-nucleus-in-guinea-pigs
#9
Rui Li, Qi Li, Xiao-Lei Chu, Tao Tao, Lan Li, Cheng-Qi He, Fang-You Gao
Synaptic plasticity plays a role during trace eyeblink conditioning (TEBC). Synaptophysin (Syn) is a major integral transmembrane protein, located particularly in the synaptic vesicles, and is considered a molecular marker of synapses. In addition, Syn immunoreactivity is an important indicator of synaptic plasticity. In this study, we used immunohistochemical techniques to assess changes in Syn expression in the cerebellar IN of guinea pigs exposed to TEBC and pseudoconditioning. Additionally, we analyzed the relationship between Syn immunoreactivity and the percentage of trace-conditioned responses...
October 19, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29050205/catalpol-protects-synaptic-proteins-from-beta-amyloid-induced-neuron-injury-and-improves-cognitive-functions-in-aged-rats
#10
Zhiming Xia, Fengfei Wang, Shuang Zhou, Rui Zhang, Fushun Wang, Jason H Huang, Erxi Wu, Yongfang Zhang, Yaer Hu
Synapse loss is one of the common factors contributing to cognitive disorders, such as Alzheimer's disease (AD), which is manifested by the impairment of basic cognitive functions including memory processing, perception, problem solving, and language. The current therapies for patients with cognitive disorders are mainly palliative; thus, regimens preventing and/or delaying dementia progression are urgently needed. In this study, we evaluated the effects of catalpol, isolated from traditional Chinese medicine Rehmannia glutinosa, on synaptic plasticity in aged rat models...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049849/regulatory-connection-between-the-expression-level-of-classical-protein-kinase-c-and-pruning-of-climbing-fibers-from-cerebellar-purkinje-cells
#11
Nobutaka Takahashi, Anton N Shuvaev, Ayumu Konno, Yasunori Matsuzaki, Masashi Watanave, Hirokazu Hirai
Cerebellar Purkinje cells (PCs) express two members of the classical protein kinase C (PKC) subfamily, namely, PKCα and PKCγ. Previous studies on PKCγ knockout (KO) mice have revealed a critical role of PKCγ in the pruning of climbing fibers (CFs) from PCs during development. The question remains as to why only PKCγ and not PKCα is involved in CF synapse elimination from PCs. To address this question, we assessed the expression levels of PKCγ and PKCα in wild-type (WT) and PKCγ KO PCs using PC-specific quantitative real-time reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical analysis...
October 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29046879/impaired-synaptic-function-is-linked-to-cognition-in-parkinson-s-disease
#12
Per Selnes, Ane Løvli Stav, Krisztina K Johansen, Atle Bjørnerud, Christopher Coello, Eirik Auning, Lisa Kalheim, Ina Selseth Almdahl, Erik Hessen, Henrik Zetterberg, Kaj Blennow, Dag Aarsland, Tormod Fladby
OBJECTIVE: Cognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloid-β species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloid-β release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloid-β, and presynaptic deposits of α-synuclein...
October 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29046631/development-of-a-bayesian-estimator-for-audio-visual-integration-a-neurocomputational-study
#13
Mauro Ursino, Andrea Crisafulli, Giuseppe di Pellegrino, Elisa Magosso, Cristiano Cuppini
The brain integrates information from different sensory modalities to generate a coherent and accurate percept of external events. Several experimental studies suggest that this integration follows the principle of Bayesian estimate. However, the neural mechanisms responsible for this behavior, and its development in a multisensory environment, are still insufficiently understood. We recently presented a neural network model of audio-visual integration (Neural Computation, 2017) to investigate how a Bayesian estimator can spontaneously develop from the statistics of external stimuli...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/29046483/deficiency-of-shank2-causes-mania-like-behavior-that-responds-to-mood-stabilizers
#14
Andrea L Pappas, Alexandra L Bey, Xiaoming Wang, Mark Rossi, Yong Ho Kim, Haidun Yan, Fiona Porkka, Lara J Duffney, Samantha M Phillips, Xinyu Cao, Jin-Dong Ding, Ramona M Rodriguiz, Henry H Yin, Richard J Weinberg, Ru-Rong Ji, William C Wetsel, Yong-Hui Jiang
Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24-/- mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29046153/potential-therapeutics-for-vascular-cognitive-impairment-and-dementia
#15
Miao-Kun Sun
As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders...
October 16, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/29045836/arc-requires-psd95-for-assembly-into-postsynaptic-complexes-involved-with-neural-dysfunction-and-intelligence
#16
Esperanza Fernández, Mark O Collins, René A W Frank, Fei Zhu, Maksym V Kopanitsa, Jess Nithianantharajah, Sarah A Lemprière, David Fricker, Kathryn A Elsegood, Catherine L McLaughlin, Mike D R Croning, Colin Mclean, J Douglas Armstrong, W David Hill, Ian J Deary, Giulia Cencelli, Claudia Bagni, Menachem Fromer, Shaun M Purcell, Andrew J Pocklington, Jyoti S Choudhary, Noboru H Komiyama, Seth G N Grant
Arc is an activity-regulated neuronal protein, but little is known about its interactions, assembly into multiprotein complexes, and role in human disease and cognition. We applied an integrated proteomic and genetic strategy by targeting a tandem affinity purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice. This allowed biochemical and proteomic characterization of native complexes in wild-type and knockout mice. We identified many Arc-interacting proteins, of which PSD95 was the most abundant...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045835/a-role-for-dystonia-associated-genes-in-spinal-gabaergic-interneuron-circuitry
#17
Juliet Zhang, Jarret A P Weinrich, Jeffrey B Russ, John D Comer, Praveen K Bommareddy, Richard J DiCasoli, Christopher V E Wright, Yuqing Li, Peter J van Roessel, Julia A Kaltschmidt
Spinal interneurons are critical modulators of motor circuit function. In the dorsal spinal cord, a set of interneurons called GABApre presynaptically inhibits proprioceptive sensory afferent terminals, thus negatively regulating sensory-motor signaling. Although deficits in presynaptic inhibition have been inferred in human motor diseases, including dystonia, it remains unclear whether GABApre circuit components are altered in these conditions. Here, we use developmental timing to show that GABApre neurons are a late Ptf1a-expressing subclass and localize to the intermediate spinal cord...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045780/mechanisms-of-activation-and-subunit-release-in-ca2-calmodulin-dependent-protein-kinase-ii
#18
Filippo Pullara, Eliana Karina Asciutto, Ignacio Jose General
Calcium/Calmodulin dependent protein kinase II is an enzyme involved in many different functions, including the so-called long-term potentiation, a mechanism that strengthens synapses in a persistent mode, and is believed to be a basic cellular mechanism for memory formation. Here we study the conformational changes of the enzyme due to phosphorylation of some key residues that are believed to drive the transition from an inhibited to an active state; it is this active state the one associated with long-term potentiation...
October 18, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29045040/neurexin-gene-family-variants-as-risk-factors-for-autism-spectrum-disorder
#19
Jia Wang, Jianhua Gong, Li Li, Yanlin Chen, Lingfei Liu, HuaiTing Gu, Xiu Luo, Fang Hou, Jiajia Zhang, Ranran Song
Increasing evidence suggests that abnormal synaptic function leads to neuronal developmental disorders and is an important component of the etiology of autism spectrum disorder (ASD). Neurexins are presynaptic cell-adhesion molecules that affect the function of synapses and mediate the conduction of nerve signals. Thus, neurexins are attractive candidate genes for autism. Since gene families have greater power to reveal genetic association than single genes, we designed this case-control study to investigate six genetic variants in three neurexin genes (NRXN1, NRXN2, and NRXN3) in a Chinese population including 529 ASD patients and 1,923 healthy controls...
October 16, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/29044770/effects-of-forced-passive-and-voluntary-exercise-on-spinal-motoneurons-changes-after-peripheral-nerve-injury
#20
Ariadna Arbat-Plana, Xavier Navarro, Esther Udina
After peripheral nerve injury, there are important changes at the spinal level that can lead to disorganization of the central circuitry and thus, compromise functional recovery even if axons are able to successfully regenerate and reinnervate their target organs. Physical rehabilitation is a promising strategy to modulate these plastic changes and thus, to improve functional recovery after damage of the nervous system. Forced exercise in a treadmill is able to partially reverse the synaptic stripping and the loss of perineuronal nets that motoneurons suffer after peripheral nerve injury in animal models...
October 17, 2017: European Journal of Neuroscience
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