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PubMed · 16234810

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

Yuan Fan·Desdemona Fricker·Darrin H Brager·Xixi Chen·Hui-Chen Lu·Raymond A Chitwood·Daniel Johnston
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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.

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BibTeXRIS

Yuan Fan, Desdemona Fricker, Darrin H Brager, Xixi Chen, Hui-Chen Lu, Raymond A Chitwood, Daniel Johnston. 2005-10-23. Activity-dependent decrease of excitability in rat hippocampal neurons through increases in I(h).. https://doi.org/10.1038/nn1568

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