Title: Activity-dependent downregulation of D-type K+ channel subunit Kv1.2 in rat hippocampal CA3 pyramidal neurons.

Authors: Jung Ho Hyun, Kisang Eom, Kyu-Hee Lee, Won-Kyung Ho, Suk-Ho Lee

Journal, date & volume: J. Physiol. (Lond.), 2013 Nov 15 , 591, 5525-40

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23981714

Abstract
The intrinsic excitability of neurons plays a critical role in the encoding of memory at Hebbian synapses and in the coupling of synaptic inputs to spike generation. It has not been studied whether somatic firing at a physiologically relevant frequency can induce intrinsic plasticity in hippocampal CA3 pyramidal cells (CA3-PCs). Here, we show that a conditioning train of 20 action potentials (APs) at 10 Hz causes a persistent reduction in the input conductance and an acceleration of the AP onset time in CA3-PCs, but not in CA1-PCs. Induction of such long-term potentiation of intrinsic excitability (LTP-IE) was accompanied by a reduction in the D-type K(+) current, and was abolished by the inhibition of endocytosis or protein tyrosine kinase (PTK). Consistently, the CA3-PCs from Kv1.2 knock-out mice displayed no LTP-IE with the same conditioning. Furthermore, the induction of LTP-IE depended on the back-propagating APs (bAPs) and intact distal apical dendrites. These results indicate that LTP-IE is mediated by the internalization of Kv1.2 channels from the distal regions of apical dendrites, which is triggered by bAP-induced dendritic Ca(2+) signalling and the consequent activation of PTK.