کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8517549 | 1556589 | 2018 | 32 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Depolarizing, inhibitory GABA type A receptor activity regulates GABAergic synapse plasticity via ERK and BDNF signaling
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
γ-aminobutyric acid (GABA) begins as the key excitatory neurotransmitter in newly forming circuits, with chloride efflux from GABA type A receptors (GABAARs) producing membrane depolarization, which promotes calcium entry, dendritic outgrowth and synaptogenesis. As development proceeds, GABAergic signaling switches to inhibitory hyperpolarizing neurotransmission. Despite the evidence of impaired GABAergic neurotransmission in neurodevelopmental disorders, little is understood on how agonist-dependent GABAAR activation controls the formation and plasticity of GABAergic synapses. We have identified a weakly depolarizing and inhibitory GABAAR response in cortical neurons that occurs during the transition period from GABAAR depolarizing excitation to hyperpolarizing inhibitory activity. We show here that treatment with the GABAAR agonist muscimol mediates structural changes that diminish GABAergic synapse strength through postsynaptic and presynaptic plasticity via intracellular Ca2+ stores, ERK and BDNF/TrkB signaling. Muscimol decreases synaptic localization of surface γ2 GABAARs and gephyrin postsynaptic scaffold while β2/3 non-γ2 GABAARs accumulate in the synapse. Concurrent with this structural plasticity, muscimol treatment decreases synaptic currents while enhancing the γ2 containing benzodiazepine sensitive GABAAR tonic current in an ERK dependent manner. We further demonstrate that GABAAR activation leads to a decrease in presynaptic GAD65 levels via BDNF/TrkB signaling. Together these data reveal a novel mechanism for agonist induced GABAergic synapse plasticity that can occur on the timescale of minutes, contributing to rapid modification of synaptic and circuit function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 128, January 2018, Pages 324-339
Journal: Neuropharmacology - Volume 128, January 2018, Pages 324-339
نویسندگان
Megan L. Brady, Jyotsna Pilli, Joshua M. Lorenz-Guertin, Sabyasachi Das, Charles E. Moon, Nicholas Graff, Tija C. Jacob,