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 (tGABA(A)) and puff-evoked GABA(A) currents (pGABA(A)). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABA(A) and tGABA(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.