Cellular/Molecular Deletion of Kv4.2 Gene Eliminates Dendritic A-Type K Current and Enhances Induction of Long-Term Potentiation

Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-termpotentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increasedgreatly viadownregulationof dendriticA-typeK currents. The channels that underlie these currents thusmay represent akey regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by using Kv4.2 knock-outmice. Deletion of theKv4.2 gene 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 dendritic Kv4.2-encoded A-type K currents led to an increase of bAPamplitude and an increase of concurrent Ca2 influx. Furthermore, CA1pyramidal neurons lacking dendriticA-typeK currents from Kv4.2 knock-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 between Kv4.2 knock-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