The A-current modulates learning via NMDA receptors containing the NR2B subunit

PLoS One. 2011;6(9):e24915. doi: 10.1371/journal.pone.0024915. Epub 2011 Sep 26.

Abstract

Synaptic plasticity involves short- and long-term events, although the molecular mechanisms that underlie these processes are not fully understood. The transient A-type K(+) current (I(A)) controls the excitability of the dendrites from CA1 pyramidal neurons by regulating the back-propagation of action potentials and shaping synaptic input. Here, we have studied how decreases in I(A) affect cognitive processes and synaptic plasticity. Using wild-type mice treated with 4-AP, an I(A) inhibitor, and mice lacking the DREAM protein, a transcriptional repressor and modulator of the I(A), we demonstrate that impairment of I(A) decreases the stimulation threshold for learning and the induction of early-LTP. Hippocampal electrical recordings in both models revealed alterations in basal electrical oscillatory properties toward low-theta frequencies. In addition, we demonstrated that the facilitated learning induced by decreased I(A) requires the activation of NMDA receptors containing the NR2B subunit. Together, these findings point to a balance between the I(A) and the activity of NR2B-containing NMDA receptors in the regulation of learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Behavior, Animal
  • CA1 Region, Hippocampal / metabolism*
  • Electrophysiology / methods
  • Memory
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Models, Genetic
  • Neuronal Plasticity*
  • Oscillometry / methods
  • Potassium / metabolism
  • Protein Structure, Tertiary
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Transmission

Substances

  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Potassium