The A-Current Modulates Learning via NMDA Receptors Containing the NR2B Subunit

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.