Muscarinic Long-Term Enhancement of Tonic and Phasic GABAAInhibition in Rat CA1 Pyramidal Neurons.
Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAAinhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAAcurrents (tGABAA) and puff-evoked GABAAcurrents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses withpGABAAandtGABAA, suggesting the contribution of two different GABAAreceptor pools. The long-term enhancement of GABAAcurrents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals.
Instituto Cajal - Consejo Superior de Investigaciones CientificasMadrid, Spain; Centre National de la Recherche Scientifique, Paris Descartes University, UMR 8118, ParisFrance.
Soledad
S
Domínguez
Instituto Cajal - Consejo Superior de Investigaciones CientificasMadrid, Spain; Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autonoma de MadridMadrid, Spain.
David
D
Fernández de Sevilla
Instituto Cajal - Consejo Superior de Investigaciones Cientificas Madrid, Spain.
Washington
W
Buño
ambient GABA; extrasynaptic receptors; inhibitory feedback; synaptic receptors; tonic current