Journal
NEUROSCIENCE
Volume 277, Issue -, Pages 610-623Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2014.07.038
Keywords
hippocampus; homeostatic intrinsic plasticity; action potential; NMDA receptor; L-type voltage-gated Ca2+ channel; potassium channel
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Funding
- ICR Start-up fund from University of Illinois at Urbana Champaign
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Homeostatic plasticity is engaged when neurons need to stabilize their synaptic strength and excitability in response to acute or prolonged destabilizing changes in global activity. Compared to the extensive studies investigating the molecular mechanisms for homeostatic synaptic plasticity, the mechanism underlying homeostatic intrinsic plasticity is largely unknown. Through whole-cell patch-clamp recording in low-density cultures of dissociated hippocampal neurons, we demonstrate here that prolonged activity blockade induced by the sodium channel blocker tetrodotoxin (TTX) leads to increased action potential firing rates. Conversely, prolonged activity enhancement induced by the A-type gamma-aminobutyric acid receptor antagonist bicuculline (BC) results in decreased firing rates. Prolonged activity enhancement also enhanced potassium (K+) current through K(v)1 channels, suggesting that changes in K+ current, in part, mediate stabilization of hippocampal neuronal excitability upon prolonged activity elevation. In contrast to the previous reports showing that L-type voltage-gated calcium (Ca2+) channels solely mediate homeostatic regulation of excitatory synaptic strength (Ibata et al., 2008; Goold and Nicoll, 2010), inhibition of N-Methyl-d-aspartate (NMDA) receptors alone mimics the elevation in firing frequency driven by prolonged TTX application, while the decrease in firing rates induced by prolonged BC treatment involves the activity of NMDA receptors and L-type voltage-gated Ca2+ channels. These results collectively provide strong evidence that alterations in Ca2+ influx through NMDA receptors and L-type voltage-gated Ca2+ channels mediate homeostatic intrinsic plasticity in hippocampal neurons in response to prolonged activity changes. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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