Referenced in: none

Automatically associated channels: HCN1

Title: Activity-dependent decrease of excitability in rat hippocampal neurons through increases in I(h).

Authors: Yuan Fan, Desdemona Fricker, Darrin H Brager, Xixi Chen, Hui-Chen Lu, Raymond A Chitwood, Daniel Johnston

Journal, date & volume: Nat. Neurosci., 2005 Nov , 8, 1542-51

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16234810

Abstract
Hippocampal long-term potentiation (LTP) induced by theta-burst pairing of Schaffer collateral inputs and postsynaptic firing is associated with localized increases in synaptic strength and dendritic excitability. Using the same protocol, we now demonstrate a decrease in cellular excitability that was blocked by the h-channel blocker ZD7288. This decrease was also induced by postsynaptic theta-burst firing alone, yet it was blocked by NMDA receptor antagonists, postsynaptic Ca2+ chelation, low concentrations of tetrodotoxin, omega-conotoxin MVIIC, calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors and a protein synthesis inhibitor. Increasing network activity with high extracellular K+ caused a similar reduction of cellular excitability and an increase in h-channel HCN1 protein. We propose that backpropagating action potentials open glutamate-bound NMDA receptors, resulting in an increase in I(h) and a decrease in overall excitability. The occurrence of such a reduction in cellular excitability in parallel with synaptic potentiation would be a negative feedback mechanism to normalize neuronal output firing and thus promote network stability.