Deletion ofKv4.2Gene Eliminates Dendritic A-Type K+Current and Enhances Induction of Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons

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Abstract
Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increased greatly via downregulation of dendritic A-type K+currents. The channels that underlie these currents thus may represent a key regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by usingKv4.2knock-out mice. Deletion of theKv4.2gene and a loss of Kv4.2 protein resulted in a specific and near-complete elimination of A-type K+currents from the apical dendrites of CA1 pyramidal neurons. The absence of dendriticKv4.2-encoded A-type K+currents led to an increase of bAP amplitude and an increase of concurrent Ca2+influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+currents fromKv4.2knock-out mice exhibited a lower threshold than those of wild-type littermates for LTP induction with the use of a theta burst pairing protocol. LTP triggered with the use of a saturating protocol, on the other hand, remained indistinguishable betweenKv4.2knock-out and wild-type neurons. Our results support the hypothesis that dendritic A-type K+channels, composed of Kv4.2 subunits, regulate action potential backpropagation and the induction of specific forms of synaptic plasticity.