NMDA receptors and L-type voltage-gated Ca2+ channels mediate the expression of bidirectional homeostatic intrinsic plasticity in cultured hippocampal neurons

Research output: Contribution to journalArticlepeer-review

Abstract

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 Kv1 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.

Original languageEnglish (US)
Pages (from-to)610-623
Number of pages14
JournalNeuroscience
Volume277
DOIs
StatePublished - Sep 26 2014

Keywords

  • Action potential
  • Hippocampus
  • Homeostatic intrinsic plasticity
  • NMDA receptor
  • Potassium channel

ASJC Scopus subject areas

  • Neuroscience(all)

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