Acetylcholine Facilitates a Depolarization-Induced Enhancement of Inhibition in Rat CA1 Pyramidal Neurons

Cholinergic mechanisms in the hippocampus regulate forms of synaptic plasticity linked with cognition and spatial navigation, but the underlying mechanisms remain largely unknown. Here, in rat hippocampal CA1 pyramidal cells under blockade of ionotropic glutamate receptors, we report that a single acetylcholine pulse and repeated depolarization activated a robust and enduring postsynaptic depolarization-induced enhancement of inhibition (DEI) that masked a presynaptic depolarization-induced suppression of inhibition (DSI). Increased cytosolic Ca2+ and M1-muscarinic receptor activation caused the rise in voltage-sensitive α5βγ2-containing γ-aminobutyric acid type-A receptors that generated DEI. In summary, this muscarinic-mediated activity-dependent plasticity rapidly transfers depolarization effects on inhibition from presynaptic suppression or DSI to postsynaptic enhancement or DEI, a change potentially relevant in behavior.This work was supported by Ministerio de Ciencia y Tecnología, BFU2005-07486 and Comunidad Autónoma de Madrid, GR/SAL/0877/2004 grants to W.B., and Ministerio de Ciencia y Tecnología, BFU2008-03488, BFU2011-23522, and BFU2013-43668P grants to D.F.d.S. S.D. was a doctoral fellow at the Instituto Cajal supported by grant (BFU2005-07486) and is now a postdoctoral fellow in the team “Synaptic Plasticity and Neural Networks” at Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8118, Université Paris Descartes, France. D.F.d.S was supported by a Ramón y Cajal Contract and is now a Professor at the “Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid”