Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons

Xixi Chen, Li Lian Yuan, Cuiping Zhao, Shari G. Birnbaum, Andreas Frick, Wonil E. Jung, Thomas L. Schwarz, J. David Sweatt, Daniel Johnston

Research output: Contribution to journalArticle

214 Citations (Scopus)

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 using Kv4.2 knock-out mice. Deletion of the Kv4.2 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 bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ 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.

Original languageEnglish (US)
Pages (from-to)12143-12151
Number of pages9
JournalJournal of Neuroscience
Volume26
Issue number47
DOIs
StatePublished - Nov 22 2006

Fingerprint

Long-Term Potentiation
Pyramidal Cells
Gene Deletion
Action Potentials
Neuronal Plasticity
Dendrites
Knockout Mice
Carisoprodol
Down-Regulation
Neurons
Proteins

Keywords

  • Backpropagating action potential
  • Dendrites
  • Hippocampus
  • K channels
  • Knock-out mouse
  • Long-term potentiation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons. / Chen, Xixi; Yuan, Li Lian; Zhao, Cuiping; Birnbaum, Shari G.; Frick, Andreas; Jung, Wonil E.; Schwarz, Thomas L.; Sweatt, J. David; Johnston, Daniel.

In: Journal of Neuroscience, Vol. 26, No. 47, 22.11.2006, p. 12143-12151.

Research output: Contribution to journalArticle

Chen, Xixi ; Yuan, Li Lian ; Zhao, Cuiping ; Birnbaum, Shari G. ; Frick, Andreas ; Jung, Wonil E. ; Schwarz, Thomas L. ; Sweatt, J. David ; Johnston, Daniel. / Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 47. pp. 12143-12151.
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AU - Chen, Xixi

AU - Yuan, Li Lian

AU - Zhao, Cuiping

AU - Birnbaum, Shari G.

AU - Frick, Andreas

AU - Jung, Wonil E.

AU - Schwarz, Thomas L.

AU - Sweatt, J. David

AU - Johnston, Daniel

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N2 - 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 using Kv4.2 knock-out mice. Deletion of the Kv4.2 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 bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ 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.

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