학술논문
Tonic GABA A Conductance Favors Spike-Timing-Dependent over Theta-Burst-Induced Long-Term Potentiation in the Hippocampus.
Document Type
Academic Journal
Author
Dembitskaya Y; RIKEN Brain Science Institute, Saitama 351-0198, Japan.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.; Wu YW; RIKEN Brain Science Institute, Saitama 351-0198, Japan.; Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.; Semyanov A; RIKEN Brain Science Institute, Saitama 351-0198, Japan alexeysemyanov@gmail.com.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.; Sechenov First Moscow State Medical University, Moscow, 119146, Russia.
Source
Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE
Subject
Language
English
Abstract
Synaptic plasticity is triggered by different patterns of network activity. Here, we investigated how LTP in CA3-CA1 synapses induced by different stimulation patterns is affected by tonic GABA A conductances in rat hippocampal slices. Spike-timing-dependent LTP was induced by pairing Schaffer collateral stimulation with antidromic stimulation of CA1 pyramidal neurons. Theta-burst-induced LTP was induced by theta-burst stimulation of Schaffer collaterals. We mimicked increased tonic GABA A conductance by bath application of 30 μm GABA. Surprisingly, tonic GABA A conductance selectively suppressed theta-burst-induced LTP but not spike-timing-dependent LTP. We combined whole-cell patch-clamp electrophysiology, two-photon Ca 2+ imaging, glutamate uncaging, and mathematical modeling to dissect the mechanisms underlying these differential effects of tonic GABA A conductance. We found that Ca 2+ transients during pairing of an action potential with an EPSP were less sensitive to tonic GABA A conductance-induced shunting inhibition than Ca 2+ transients induced by EPSP burst. Our results may explain how different forms of memory are affected by increasing tonic GABA A conductances under physiological or pathologic conditions, as well as under the influence of substances that target extrasynaptic GABA A receptors (e.g., neurosteroids, sedatives, antiepileptic drugs, and alcohol). SIGNIFICANCE STATEMENT Brain activity is associated with neuronal firing and synaptic signaling among neurons. Synaptic plasticity represents a mechanism for learning and memory. However, some neurotransmitters that escape the synaptic cleft or are released by astrocytes can target extrasynaptic receptors. Extrasynaptic GABA A receptors mediate tonic conductances that reduce the excitability of neurons by shunting. This results in the decreased ability for neurons to fire action potentials, but when action potentials are successfully triggered, tonic conductances are unable to reduce them significantly. As such, tonic GABA A conductances have minimal effects on spike-timing-dependent synaptic plasticity while strongly attenuating the plasticity evoked by EPSP bursts. Our findings shed light on how changes in tonic conductances can selectively affect different forms of learning and memory.
(Copyright © 2020 the authors.)
(Copyright © 2020 the authors.)