Muscarinic Long-Term Enhancement of Tonic and Phasic GABA A Inhibition 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 (GABA _A Rs). Although, the enhancing effects of ACh on GABA _A Rs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABA _A inhibition 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 GABA _A Rs. 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 GABA _A currents ( t GABA _A ) and puff-evoked GABA _A currents ( p GABA _A ). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with p GABA _A and t GABA _A , suggesting the contribution of two different GABA _A receptor pools. The long-term enhancement of GABA _A currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals.