scholarly journals Single and Repeated Administration of Methylphenidate Modulates Synaptic Plasticity in Opposite Directions via Insertion of AMPA Receptors in Rat Hippocampal Neurons

2018 ◽  
Vol 9 ◽  
Author(s):  
Claudia Carvallo ◽  
Darwin Contreras ◽  
Gonzalo Ugarte ◽  
Ricardo Delgado ◽  
Floria Pancetti ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Repeated Administration ◽  
Single And Repeated Administration

scholarly journals Constitutive ghrelin receptor activity modulates AMPA receptor traffic and supports memory formation

2020 ◽  
Author(s):  
Luís F. Ribeiro ◽  
Tatiana Catarino ◽  
Mário Carvalho ◽  
Sandra D. Santos ◽  
Luísa Cortes ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Physiological Role ◽  
Long Term Potentiation ◽  
Receptor Activity ◽  
Constitutive Activity ◽  
Ghrelin Receptor

AbstractThe ability of animals to store and retrieve food caches in the wild requires the integration of biological signals of hunger, satiety and memory. The role of ghrelin in regulating feeding and memory makes ghrelin receptors an important target to shape the required cellular and molecular responses. We investigated the effects of the high ligand-independent activity of the ghrelin receptor on the physiology of excitatory synapses. Blocking this type of activity produced a decrease in the synaptic content of AMPA receptors in hippocampal neurons and a reduction in GluA1 phosphorylation at Ser845. Impaired constitutive activity from the ghrelin receptor increased surface diffusion of AMPA receptors and impaired AMPA receptor synaptic delivery mediated by chemical long-term potentiation. These observations support a role for the constitutive activity of the ghrelin receptor in regulating AMPA receptor trafficking under basal conditions and synaptic plasticity. Accordingly, we found that blocking the ghrelin receptor constitutive activity impairs spatial and recognition memory.Impact statementThis work uncovers a role for the constitutive activity of the ghrelin receptor in memory, and in the regulation of the synaptic levels of AMPA receptors, their mobility and synaptic plasticity. Underscoring the importance of deciphering the physiological role of constitutive ghrelin receptor activity, ghrelin receptor inverse agonism is now being considered as a therapy to treat alcohol use disorder.

scholarly journals Imbalanced post- and extrasynaptic SHANK2A functions during development affect social behavior in SHANK2-mediated neuropsychiatric disorders

2021 ◽  
Author(s):  
Ahmed Eltokhi ◽  
Miguel A. Gonzalez-Lozano ◽  
Lars-Lennart Oettl ◽  
Andrey Rozov ◽  
Claudia Pitzer ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Social Interaction ◽  
Social Behavior ◽  
Ampa Receptors ◽  
Signal To Noise Ratio ◽  
Signal Transmission ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Strong Impact ◽  
Odor Processing

AbstractMutations in SHANK genes play an undisputed role in neuropsychiatric disorders. Until now, research has focused on the postsynaptic function of SHANKs, and prominent postsynaptic alterations in glutamatergic signal transmission have been reported in Shank KO mouse models. Recent studies have also suggested a possible presynaptic function of SHANK proteins, but these remain poorly defined. In this study, we examined how SHANK2 can mediate electrophysiological, molecular, and behavioral effects by conditionally overexpressing either wild-type SHANK2A or the extrasynaptic SHANK2A(R462X) variant. SHANK2A overexpression affected pre- and postsynaptic targets and revealed a reversible, development-dependent autism spectrum disorder-like behavior. SHANK2A also mediated redistribution of Ca2+-permeable AMPA receptors between apical and basal hippocampal CA1 dendrites, leading to impaired synaptic plasticity in the basal dendrites. Moreover, SHANK2A overexpression reduced social interaction and increased the excitatory noise in the olfactory cortex during odor processing. In contrast, overexpression of the extrasynaptic SHANK2A(R462X) variant did not impair hippocampal synaptic plasticity, but still altered the expression of presynaptic/axonal signaling proteins. We also observed an attention-deficit/hyperactivity-like behavior and improved social interaction along with enhanced signal-to-noise ratio in cortical odor processing. Our results suggest that the disruption of pre- and postsynaptic SHANK2 functions caused by SHANK2 mutations has a strong impact on social behavior. These findings indicate that pre- and postsynaptic SHANK2 actions cooperate for normal neuronal function, and that an imbalance between these functions may lead to different neuropsychiatric disorders.

Molecular Basis for Functional Differences of AMPA-Subtype Glutamate Receptors

Physiology ◽  
1996 ◽  
Vol 11 (2) ◽  
pp. 77-82 ◽  
Author(s):  
S Ozawa ◽  
J Rossier
Keyword(s):  
Polymerase Chain Reaction ◽  
Ampa Receptors ◽  
Molecular Basis ◽  
Hippocampal Neurons ◽  
Polymerase Chain Reaction Amplification ◽  
Inward Rectification ◽  
Chain Reaction ◽  
Functional Differences ◽  
Reaction Amplification ◽  
Polymerase Chain

To trace the molecular basis of functional properties of native a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, we have coupled patch-clamp recordings and reverse transcription followed by polymerase chain reaction amplification. AMPA receptors lacking the GluR2 subunit in a population of hippocampal neurons exhibited a strong inward rectification and were highly permeable to Ca2+.

scholarly journals Regulation of GABAergic synapse formation and plasticity by GSK3β-dependent phosphorylation of gephyrin

2010 ◽  
Vol 108 (1) ◽  
pp. 379-384 ◽  
Author(s):  
Shiva K. Tyagarajan ◽  
Himanish Ghosh ◽  
Gonzalo E. Yévenes ◽  
Irina Nikonenko ◽  
Claire Ebeling ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Neurons ◽  
Glycogen Synthase ◽  
Phosphorylation Site ◽  
Scaffolding Protein ◽  
Scaffolding Proteins ◽  
Gabaergic Synapse ◽  
Gabaergic Synapses

Postsynaptic scaffolding proteins ensure efficient neurotransmission by anchoring receptors and signaling molecules in synapse-specific subcellular domains. In turn, posttranslational modifications of scaffolding proteins contribute to synaptic plasticity by remodeling the postsynaptic apparatus. Though these mechanisms are operant in glutamatergic synapses, little is known about regulation of GABAergic synapses, which mediate inhibitory transmission in the CNS. Here, we focused on gephyrin, the main scaffolding protein of GABAergic synapses. We identify a unique phosphorylation site in gephyrin, Ser270, targeted by glycogen synthase kinase 3β (GSK3β) to modulate GABAergic transmission. Abolishing Ser270 phosphorylation increased the density of gephyrin clusters and the frequency of miniature GABAergic postsynaptic currents in cultured hippocampal neurons. Enhanced, phosphorylation-dependent gephyrin clustering was also induced in vitro and in vivo with lithium chloride. Lithium is a GSK3β inhibitor used therapeutically as mood-stabilizing drug, which underscores the relevance of this posttranslational modification for synaptic plasticity. Conversely, we show that gephyrin availability for postsynaptic clustering is limited by Ca2+-dependent gephyrin cleavage by the cysteine protease calpain-1. Together, these findings identify gephyrin as synaptogenic molecule regulating GABAergic synaptic plasticity, likely contributing to the therapeutic action of lithium.

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