title: The A-current modulates learning via NMDA receptors containing the NR2B subunit.
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.
authors.affiliation: División de Neurociencias, Universidad Pablo de Olavide de Sevilla, Sevilla, Spain. angela.fontan@cabimer.es
authors.forename: Ángela
authors.initials: Á
authors.lastname: Fontán-Lozano
authors.forename: Irene
authors.initials: I
authors.lastname: Suárez-Pereira
authors.forename: David
authors.initials: D
authors.lastname: González-Forero
authors.forename: Angel Manuel
authors.initials: AM
authors.lastname: Carrión
mesh_terms: D000200:Action Potentials; D000818:Animals; D001522:Behavior, Animal; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D004594:Electrophysiology / Q000379:methods; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008957:Models, Genetic; D009473:Neuronal Plasticity; D009991:Oscillometry / Q000379:methods; D011188:Potassium / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D011188:Potassium