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Frontiers in Synaptic Neuroscience

Roman Blome, Willi Bach, Xiati Guli, Katrin Porath, Tina Sellmann, Christian G Bien, Rüdiger Köhling, Timo Kirschstein
Purpose : Autoantibodies against NMDA receptors (NMDAR) in the cerebrospinal fluid (CSF) from anti-NMDAR encephalitis patients have been suggested to be pathogenic since in previous studies using patient CSF, NMDAR-dependent processes such as long-term potentiation (LTP) were compromised. However, autoantibodies may represent a family of antibodies targeted against different epitopes, and CSF may contain further autoantibodies. Here, we tested the specificity of the autoantibody by comparing NMDAR-dependent and NMDAR-independent LTP within the same hippocampal subfield, CA3, using CSF samples from four anti-NMDAR encephalitis patients and three control patients...
2018: Frontiers in Synaptic Neuroscience
Astrid Rollenhagen, Ora Ohana, Kurt Sätzler, Claus C Hilgetag, Dietmar Kuhl, Joachim H R Lübke
Cortical computations rely on functionally diverse and highly dynamic synapses. How their structural composition affects synaptic transmission and plasticity and whether they support functional diversity remains rather unclear. Here, synaptic boutons on layer 5B (L5B) pyramidal neurons in the adult rat barrel cortex were investigated. Simultaneous patch-clamp recordings from synaptically connected L5B pyramidal neurons revealed great heterogeneity in amplitudes, coefficients of variation (CVs), and failures (F%) of EPSPs...
2018: Frontiers in Synaptic Neuroscience
Ahmet S Ozcan, Mehmet S Ozcan
Structural plasticity, characterized by the formation and elimination of synapses, plays a big role in learning and long-term memory formation in the brain. The majority of the synapses in the neocortex occur between the axonal boutons and dendritic spines. Therefore, understanding the dynamics of the dendritic spine growth and elimination can provide key insights to the mechanisms of structural plasticity. In addition to learning and memory formation, the connectivity of neural networks affects cognition, perception, and behavior...
2018: Frontiers in Synaptic Neuroscience
Jivan Khlghatyan, Jean-Martin Beaulieu
Dopamine receptors and related signaling pathways have long been implicated in pathophysiology and treatment of mental illnesses, including schizophrenia and bipolar disorder. Dopamine signaling may impact neuronal activity by modulation of glutamate neurotransmission. Recent evidence indicates a direct and/or indirect involvement of fragile X-related family proteins (FXR) in the regulation and mediation of dopamine receptor functions. FXRs consists of fragile X mental retardation protein 1 (Fmr1/FMRP) and its autosomal homologs Fxr1 and Fxr2...
2018: Frontiers in Synaptic Neuroscience
Claire Guerrier, David Holcman
Calcium diffusion in the thin 100 nm layer located between the plasma membrane and docked vesicles in the pre-synaptic terminal of neuronal cells mediates vesicular fusion and synaptic transmission. Accounting for the narrow-cusp geometry located underneath the vesicle is a key ingredient that defines the probability and the time scale of calcium diffusion to bind calcium sensors for the initiation of vesicular release. We review here the time scale, the calcium binding dynamics and the consequences for asynchronous versus synchronous release...
2018: Frontiers in Synaptic Neuroscience
Jary Y Delgado, Paul R Selvin
Calcium dynamics in presynaptic terminals regulate the response dynamics of most central excitatory synapses. However, this dogma has been challenged by the hypothesis that mobility of the postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype glutamate receptors (AMPAR) plays a role in tuning fast excitatory synaptic transmission. In this review, we reevaluate the factors regulating postsynaptic AMPAR mobility, reassess the modeling parameters, analyze the experimental tools, and end by providing alternative ideas stemming from recent results...
2018: Frontiers in Synaptic Neuroscience
Heather McGowan, Vincent R Mirabella, Aula Hamod, Aziz Karakhanyan, Nicole Mlynaryk, Jennifer C Moore, Jay A Tischfield, Ronald P Hart, Zhiping P Pang
Non-coding RNA, including microRNA (miRNA) serves critical regulatory functions in the developing brain. The let-7 family of miRNAs has been shown to regulate neuronal differentiation, neural subtype specification, and synapse formation in animal models. However, the regulatory role of human let-7c (hsa-let-7c) in human neuronal development has yet to be examined. Let-7c is encoded on chromosome 21 in humans and therefore may be overexpressed in human brains in Trisomy 21 (T21), a complex neurodevelopmental disorder...
2018: Frontiers in Synaptic Neuroscience
Dasiel O Borroto-Escuela, Miguel Perez De La Mora, Paul Manger, Manuel Narváez, Sarah Beggiato, Minerva Crespo-Ramírez, Gemma Navarro, Karolina Wydra, Zaida Díaz-Cabiale, Alicia Rivera, Luca Ferraro, Sergio Tanganelli, Małgorzata Filip, Rafael Franco, Kjell Fuxe
This perspective article provides observations supporting the view that nigro-striatal dopamine neurons and meso-limbic dopamine neurons mainly communicate through short distance volume transmission in the um range with dopamine diffusing into extrasynaptic and synaptic regions of glutamate and GABA synapses. Based on this communication it is discussed how volume transmission modulates synaptic glutamate transmission onto the D1R modulated direct and D2R modulated indirect GABA pathways of the dorsal striatum...
2018: Frontiers in Synaptic Neuroscience
Annette Gower, Mario Tiberi
Dopamine, a major neurotransmitter, plays a role in a wide range of brain sensorimotor functions. Parkinson's disease and schizophrenia are two major human neuropsychiatric disorders typically associated with dysfunctional dopamine activity levels, which can be alleviated through the druggability of the dopaminergic systems. Meanwhile, several studies suggest that optimal brain dopamine activity levels are also significantly impacted in other serious neurological conditions, notably stroke, but this has yet to be fully appreciated at both basic and clinical research levels...
2018: Frontiers in Synaptic Neuroscience
Keerthi Thirtamara Rajamani, Shlomo Wagner, Valery Grinevich, Hala Harony-Nicolas
The neuropeptide oxytocin (OXT) is a crucial mediator of parturition and milk ejection and a major modulator of various social behaviors, including social recognition, aggression and parenting. In the past decade, there has been significant excitement around the possible use of OXT to treat behavioral deficits in neurodevelopmental disorders, including autism spectrum disorder (ASD). Yet, despite the fast move to clinical trials with OXT, little attention has been paid to the possibility that the OXT system in the brain is perturbed in these disorders and to what extent such perturbations may contribute to social behavior deficits...
2018: Frontiers in Synaptic Neuroscience
Andrew D Bolton, Martha Constantine-Paton
Working memory is the ability to hold information "online" over a time delay in order to perform a task. This kind of memory is encoded in the brain by persistent neural activity that outlasts the presentation of a stimulus. Patients with schizophrenia perform poorly in working memory tasks that require the brief memory of a target location in space. This deficit indicates that persistent neural activity related to spatial locations may be impaired in the disease. At the circuit level, many studies have shown that NMDA receptors and the dopamine system are involved in both schizophrenia pathology and working memory-related persistent activity...
2018: Frontiers in Synaptic Neuroscience
Hadi Zarif, Salma Hosseiny, Agnès Paquet, Kevin Lebrigand, Marie-Jeanne Arguel, Julie Cazareth, Anne Lazzari, Catherine Heurteaux, Nicolas Glaichenhaus, Joëlle Chabry, Alice Guyon, Agnès Petit-Paitel
Living in an enriched environment (EE) benefits health by acting synergistically on various biological systems including the immune and the central nervous systems. The dialog between the brain and the immune cells has recently gained interest and is thought to play a pivotal role in beneficial effects of EE. Recent studies show that T lymphocytes have an important role in hippocampal plasticity, learning, and memory, although the precise mechanisms by which they act on the brain remain elusive. Using a mouse model of EE, we show here that CD4+ T cells are essential for spinogenesis and glutamatergic synaptic function in the CA of the hippocampus...
2018: Frontiers in Synaptic Neuroscience
Hansen Wang
The complexity and delicacy of human brain make it challenging to recapitulate its development, function and disorders. Brain organoids derived from human pluripotent stem cells (PSCs) provide a new tool to model both normal and pathological human brain, and greatly enhance our ability to study brain biology and diseases. Currently, human brain organoids are increasingly used in modeling neurological disorders and relative therapeutic discovery. This review article focuses on recent advances in human brain organoid system and its application in disease modeling...
2018: Frontiers in Synaptic Neuroscience
Elaine Del-Bel, Francisco F De-Miguel
This review article deals with the mechanisms of extrasynaptic release of transmitter substances, namely the release from the soma, axon and dendrites in the absence of postsynaptic counterparts. Extrasynaptic release occurs by exocytosis or diffusion. Spillover from the synaptic cleft also contributes to extrasynaptic neurotransmission. Here, we first describe two well-known examples of exocytosis from the neuronal soma, which may release copious amounts of transmitter for up to hundreds of seconds after electrical stimulation...
2018: Frontiers in Synaptic Neuroscience
Allie J Widman, Amy E Stewart, Elise M Erb, Elizabeth Gardner, Lori L McMahon
In the past 20 years, ketamine has become a promising treatment for Major Depressive Disorder (MDD) due to its rapid and sustain antidepressant effects in patients. A single ketamine treatment causes improvement in depressive symptoms within hours and can last weeks, long after it is eliminated. Previous studies have demonstrated increased synaptic plasticity at CA3-CA1 synapses in hippocampus (HPC) 24 h post ketamine treatment suggesting increased activity-dependent hippocampal function may underlie the antidepressant effects of ketamine...
2018: Frontiers in Synaptic Neuroscience
Nicholas M Graziane, Peter A Neumann, Yan Dong
The lateral habenula (LHb) regulates reward learning and controls the updating of reward-related information. Drugs of abuse have the capacity to hijack the cellular and neurocircuit mechanisms mediating reward learning, forming non-adaptable, compulsive behaviors geared toward obtaining illicit substances. Here, we discuss current findings demonstrating how drugs of abuse alter intrinsic and synaptic LHb neuronal function. Additionally, we discuss evidence for how drug-induced LHb alterations may affect the ability to predict reward, potentially facilitating an addiction-like state...
2018: Frontiers in Synaptic Neuroscience
Simone Hagmeyer, Ann Katrin Sauer, Andreas M Grabrucker
The loss of one copy of SHANK3 (SH3 and multiple ankyrin repeat domains 3) in humans highly contributes to Phelan McDermid syndrome (PMDS). In addition, SHANK3 was identified as a major autism candidate gene. Interestingly, the protein encoded by the SHANK3 gene is regulated by zinc. While zinc deficiency depletes synaptic pools of Shank3, increased zinc levels were shown to promote synaptic scaffold formation. Therefore, the hypothesis arises that patients with PMDS and Autism caused by Shankopathies, having one intact copy of SHANK3 left, may benefit from zinc supplementation, as elevated zinc may drive remaining Shank3 into the post-synaptic density (PSD) and may additional recruit Shank2, a second zinc-dependent member of the SHANK gene family...
2018: Frontiers in Synaptic Neuroscience
Nicolas Unsain, Fernando D Stefani, Alfredo Cáceres
Neurons are the most asymmetric cell types, with their axons commonly extending over lengths that are thousand times longer than the diameter of the cell soma. Fluorescence nanoscopy has recently unveiled that actin, spectrin and accompanying proteins form a membrane-associated periodic skeleton (MPS) that is ubiquitously present in mature axons from all neuronal types evaluated so far. The MPS is a regular supramolecular protein structure consisting of actin "rings" separated by spectrin tetramer "spacers"...
2018: Frontiers in Synaptic Neuroscience
Mellanie Fontes-Dutra, Júlio Santos-Terra, Iohanna Deckmann, Gustavo Brum Schwingel, Gustavo Della-Flora Nunes, Mauro Mozael Hirsch, Guilherme Bauer-Negrini, Rudimar S Riesgo, Victorio Bambini-Júnior, Cecília Hedin-Pereira, Carmem Gottfried
Autism spectrum disorder (ASD) is characterized by impairments in both social communication and interaction and repetitive or stereotyped behaviors. Although its etiology remains unknown, genetic and environmental risk factors have been associated with this disorder, including the exposure to valproic acid (VPA) during pregnancy. Resveratrol (RSV) is an anti-inflammatory and antioxidant molecule known to prevent social impairments in the VPA animal model of autism. This study aimed to analyze the effects of prenatal exposure to VPA, as well as possible preventive effects of RSV, on sensory behavior, the localization of GABAergic parvalbumin (PV+ ) neurons in sensory brain regions and the expression of proteins of excitatory and inhibitory synapses...
2018: Frontiers in Synaptic Neuroscience
Sha-Sha Yang, Yan-Chun Li, Austin A Coley, Linda A Chamberlin, Ping Yu, Wen-Jun Gao
H-current, also known as hyperpolarization-activated current (Ih), is an inward current generated by the hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels. Ih plays an essential role in regulating neuronal properties, synaptic integration and plasticity, and synchronous activity in the brain. As these biological factors change across development, the brain undergoes varying levels of vulnerability to disorders like schizophrenia that disrupt prefrontal cortex (PFC)-dependent function...
2018: Frontiers in Synaptic Neuroscience
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