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https://www.readbyqxmd.com/read/28238551/molecular-mechanism-of-ampa-receptor-modulation-by-tarp-stargazin
#1
Anat Ben-Yaacov, Moshe Gillor, Tomer Haham, Alon Parsai, Mohammad Qneibi, Yael Stern-Bach
AMPA receptors (AMPARs) mediate the majority of fast excitatory transmission in the brain and critically contribute to synaptic plasticity and pathology. AMPAR trafficking and gating are tightly controlled by auxiliary transmembrane AMPAR regulatory proteins (TARPs). Here, using systematic domain swaps with the TARP-insensitive kainate receptor GluK2, we show that AMPAR interaction with the prototypical TARP stargazin/γ2 primarily involves the AMPAR membrane domains M1 and M4 of neighboring subunits, initiated or stabilized by the AMPAR C-tail, and that these interactions are sufficient to enable full receptor modulation...
February 17, 2017: Neuron
https://www.readbyqxmd.com/read/28238547/hallmarks-of-alzheimer-s-disease-in-stem-cell-derived-human-neurons-transplanted-into-mouse-brain
#2
Ira Espuny-Camacho, Amaia M Arranz, Mark Fiers, An Snellinx, Kunie Ando, Sebastian Munck, Jerome Bonnefont, Laurie Lambot, Nikky Corthout, Lorna Omodho, Elke Vanden Eynden, Enrico Radaelli, Ina Tesseur, Selina Wray, Andreas Ebneth, John Hardy, Karelle Leroy, Jean-Pierre Brion, Pierre Vanderhaeghen, Bart De Strooper
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration...
February 15, 2017: Neuron
https://www.readbyqxmd.com/read/28237844/characterization-of-the-cystine-glutamate-antiporter-in-cultured-bergmann-glia-cells
#3
Edna Suárez-Pozos, Zila Martínez-Lozada, Orquidia G Mendez-Flores, Alain M Guillem, Luisa C Hernández-Kelly, Francisco Castelán, Tatiana N Olivares-Bañuelos, Donaji Chi-Castañeda, Mustapha Najimi, Arturo Ortega
Glutamate, the major excitatory transmitter in the vertebrate brain is a potent neurotoxin through the over-stimulation of its specific membrane receptors. In accordance, a tight regulation of its extracellular levels by plasma membrane transporters is present. A family of excitatory amino acid transporters is expressed in neurons and glia cells and is responsible of the removal of the neurotransmitter from the synaptic cleft. Glial transporters account for more than 80% of the brain uptake activity. The cystine/glutamate antiporter is another plasma membrane-bound protein critically involved in glutamatergic transmission...
February 22, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28231043/transient-oxytocin-signaling-primes-the-development-and-function-of-excitatory-hippocampal-neurons
#4
Silvia Ripamonti, Mateusz C Ambrozkiewicz, Francesca Guzzi, Marta Gravati, Gerardo Biella, Ingo Bormuth, Matthieu Hammer, Liam P Tuffy, Albrecht Sigler, Hiroshi Kawabe, Katsuhiko Nishimori, Mauro Toselli, Nils Brose, Marco Parenti, JeongSeop Rhee
Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure in vitro inhibits the development of hippocampal glutamatergic neurons, leading to reduced dendrite complexity, synapse density, and excitatory transmission, while sparing GABAergic neurons...
23, 2017: ELife
https://www.readbyqxmd.com/read/28230208/optogenetic-activation-of-vglut2-expressing-excitatory-neurons-blocks-epileptic-seizure-like-activity-in-the-mouse-entorhinal-cortex
#5
Latefa Yekhlef, Gian Luca Breschi, Stefano Taverna
We investigated whether an anti-epileptic effect is obtained by selectively activating excitatory neurons expressing ChR2 under the promoter for the synaptic vesicular glutamate transporter 2 (VGLUT2). VGLUT2-expressing cells were optically stimulated while local field potential and whole-cell patch-clamp recordings were performed in mouse entorhinal cortical slices perfused with the proconvulsive compound 4-aminopyridine (4-AP). In control conditions, blue light flashes directly depolarized the majority of putative glutamatergic cells, which in turn synaptically excited GABAergic interneurons...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228252/complete-disruption-of-the-kainate-receptor-gene-family-results-in-corticostriatal-dysfunction-in-mice
#6
Jian Xu, John J Marshall, Herman B Fernandes, Toshihiro Nomura, Bryan A Copits, Daniele Procissi, Susumu Mori, Lei Wang, Yongling Zhu, Geoffrey T Swanson, Anis Contractor
Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228251/spatial-and-temporal-regulation-of-receptor-endocytosis-in-neuronal-dendrites-revealed-by-imaging-of-single-vesicle-formation
#7
Morgane Rosendale, Damien Jullié, Daniel Choquet, David Perrais
Endocytosis in neuronal dendrites is known to play a critical role in synaptic transmission and plasticity such as long-term depression (LTD). However, the inability to detect endocytosis directly in living neurons has hampered studies of its dynamics and regulation. Here, we visualized the formation of individual endocytic vesicles containing pHluorin-tagged receptors with high temporal resolution in the dendrites of cultured hippocampal neurons. We show that transferrin receptors (TfRs) are constitutively internalized at optically static clathrin-coated structures...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226818/stochastic-modeling-of-spontaneous-bursting-activity-to-simulate-neural-responses-of-in-vitro-networks-on-multielectrode-arrays
#8
Gaetano Valenza, Gianluca Vannucci, Enzo Wanke, Enzo Pasquale Scilingo, Gaetano Valenza, Gianluca Vannucci, Enzo Wanke, Enzo Pasquale Scilingo, Gaetano Valenza, Enzo Wanke, Gianluca Vannucci, Enzo Pasquale Scilingo
The study of neuronal bursting activity, observed in cell-culture, is physiologically important because is correlated with synaptic transmission, plasticity, and information processing. However, besides strong ethical issues related to the use of animal models, there are many limitations due to experimental setup and neural signaling acquisition. In this study, we propose a stochastic modeling approach to simulate neural dynamics observed in networks of neocortical neurons from an ex vivo normal mouse. Specifically, we devised a stochastic version of the Izhichevich's model of cortical neurons, and simulated a network of excitatory and inhibitory neurons also accounting for cell signaling delays...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223480/in-vivo-imaging-reveals-that-pregabalin-inhibits-cortical-spreading-depression-and-propagation-to-subcortical-brain-structures
#9
Stuart M Cain, Barry Bohnet, Jeffrey LeDue, Andrew C Yung, Esperanza Garcia, John R Tyson, Sascha R A Alles, Huili Han, Arn M J M van den Maagdenberg, Piotr Kozlowski, Brian A MacVicar, Terrance P Snutch
Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wild-type (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the CaV2...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28222692/hashimoto-s-encephalitis-associated-with-ampar2-antibodies-a-case-report
#10
Mingqin Zhu, Xuefan Yu, Caiyun Liu, Chenchen Duan, Chunxiao Li, Jie Zhu, Ying Zhang
BACKGROUND: Hashimoto's encephalitis (HE) is a rare neurological complication of Hashimoto's thyroiditis (HT), while limbic encephalitis (LE) is an autoimmune inflammatory disorder frequently associated with anti-neuronal antibodies. The glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) is important for synaptic transmission, memory, and learning. The etiology of HE remains unclear. We present a case of HE with antibodies to AMPAR2 both in the serum and cerebrospinal fluid...
February 21, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28222617/presynaptic-calmodulin-targets-lessons-from-structural-proteomics
#11
Noa Lipstein, Melanie Göth, Christine Piotrowski, Kevin Pagel, Andrea Sinz, Olaf Jahn
Calmodulin (CaM) is a highly conserved Ca(2+)-binding protein that is exceptionally abundant in the brain. In the presynaptic compartment of neurons, CaM transduces changes in Ca(2+) concentration into the regulation of synaptic transmission dynamics. Areas covered: We review selected literature including published CaM interactor screens and outline established and candidate presynaptic CaM targets. We present a workflow of biochemical and structural proteomic methods that were used to identify and characterize the interactions between CaM and Munc13 proteins...
March 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28222295/locomotion-control-from-the-periphery
#12
Claire Wyart
Studies of the neural control of locomotion have tended to focus on the modulation of motoneuron firing by premotor neurons; new work indicates that the regulation of synaptic transmission at the neuromuscular junction can also be important, revealing an inverse relationship between input resistance and synaptic output in motoneurons.
February 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28221305/a-novel-missense-variant-in-the-agrn-gene-congenital-myasthenic-syndrome-presenting-with-head-drop
#13
Mert Karakaya, Ozge Ceyhan-Birsoy, Alan H Beggs, Haluk Topaloglu
Congenital myasthenic syndromes (CMS) are a heterogeneous group of diseases of the neuromuscular junction caused by compromised synaptic transmission. Clinical features include early-onset weakness of limbs and oculobulbar muscles resulting in hypotonia, bulbar paresis, ptosis, and hypoventilation. The first dropped head syndrome in children were detected in 2 patients with LMNA and SEPN1 mutations. We report a 17-month-old boy with dropped head and limb-girdle weakness, who had no ptosis or ophthalmoplegia at presentation...
March 2017: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/28220838/pan-neurexin-perturbation-results-in-compromised-synapse-stability-and-a-reduction-in-readily-releasable-synaptic-vesicle-pool-size
#14
Dylan P Quinn, Annette Kolar, Michael Wigerius, Rachel N Gomm-Kolisko, Hanine Atwi, James P Fawcett, Stefan R Krueger
Neurexins are a diverse family of cell adhesion molecules that localize to presynaptic specializations of CNS neurons. Heterologous expression of neurexins in non-neuronal cells leads to the recruitment of postsynaptic proteins in contacting dendrites of co-cultured neurons, implicating neurexins in synapse formation. However, isoform-specific knockouts of either all α- or all β-neurexins show defects in synaptic transmission but an unaltered density of glutamatergic synapses, a finding that argues against an essential function of neurexins in synaptogenesis...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219682/epilepsy-and-synaptic-proteins
#15
REVIEW
Yuko Fukata, Masaki Fukata
Throughout history, epilepsy affects about 1-2% of the population worldwide. Epilepsy can be caused by traumatic brain injury, exposure to certain toxins and drugs, and mutations of genes that often encode synaptic proteins. In addition to conventional linkage and association studies, the recent trio exome sequencing in epilepsy and proteomic analysis in autoimmune synaptopathies have accelerated identification of novel epilepsy-related proteins, most of which play critical roles in synaptic transmission. Furthermore, super-resolution microscopy analysis has revealed subsynaptic nanoscale distribution of presynaptic and postsynaptic proteins and suggests a precise trans-synaptic alignment of neurotransmitter release to receptors...
February 17, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28219180/-advances-in-effect-of-unilateral-auditory-deprivation-on-sound-localization
#16
J F Liu, J S Dai, N Y Wang
In patients with single-sided deafness (SSD), the interaural time difference and the interaural level difference signals are insufficient or missing, which result in the lack of sound localization ability and the decrease of speech comprehension in the noise environments. SSD can also cause the morphological and functional changes of the central auditory system, resulting in auditory deprivation. In early stage of the development, the auditory center is more susceptible to ambient environment and auditory inputs...
February 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28215989/klotho-regulates-ca1-hippocampal-synaptic-plasticity
#17
Qin Li, Hai T Vo, Jing Wang, Stephanie Fox-Quick, Lynn E Dobrunz, Gwendalyn D King
Global klotho overexpression extends lifespan while global klotho-deficiency shortens it. As well, klotho protein manipulations inversely regulate cognitive function. Mice without klotho develop rapid onset cognitive impairment before they are 2months old. Meanwhile, adult mice overexpressing klotho show enhanced cognitive function, particularly in hippocampal-dependent tasks. The cognitive enhancing effects of klotho extend to humans with a klotho polymorphism that increases circulating klotho and executive function...
February 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28214986/astrocyte-sodium-signalling-and-panglial-spread-of-sodium-signals-in-brain-white-matter
#18
Behrouz Moshrefi-Ravasdjani, Evelyn L Hammel, Karl W Kafitz, Christine R Rose
In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28214378/calcium-signaling-through-l-type-calcium-channels-role-in-pathophysiology-of-spinal-nociceptive-transmission
#19
REVIEW
Olivier Roca-Lapirot, Houda Radwani, Franck Aby, Frédéric Nagy, Marc Landry Pascal Fossat
L-type voltage-gated calcium channels (VGCCs) are ubiquitous channels in the central nervous system. L-type calcium channels (LTCs) are mostly post-synaptic channels regulating neuronal firing and gene expression. They play a role in important physio-pathological processes such as learning and memory, Parkinson's disease, autism and, as recognized more recently, in the pathophysiology of pain processes. Classically, the fundamental role of these channels in cardiovascular functions has limited the use of classical molecules to treat LTC-dependent disorders...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213519/an-extra-amino-acid-residue-in-transmembrane-domain-10-of-the-gaba-transporter-gat-1-is-required-for-efficient-ion-coupled-transport
#20
Oshrat Dayan, Anu Nagarajan, Raven Shah, Assaf Ben-Yona, Lucy R Forrest, Baruch I Kanner
The GABA transporter GAT-1 mediates electrogenic transport of its substrate together with sodium and chloride. It is a member of the neurotransmitter:sodium:symporters, which are crucial for synaptic transmission. Compared to all other neurotransmitter:sodium:symporters, GAT-1 and the other members of the GABA transporter subfamily, all contain an extra amino acid residue at or near a conserved glycine in transmembrane segment 10. Therefore, we studied the functional impact of deletion and replacement mutants of Gly-457, and its two adjacent residues in GAT-1...
February 17, 2017: Journal of Biological Chemistry
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