Inhibition of α7-containing nicotinic ACh receptors by muscarinic M1 ACh receptors in rat hippocampal CA1 interneurones in slices

Cys-loop ligand-gated nicotinic ACh receptors (nAChRs) and G protein-coupled muscarinic ACh receptors (mAChRs) are expressed on rat hippocampal interneurones where they can regulate excitability, synaptic communication and cognitive function. Even though both nAChRs and mAChRs appear to co-localize to the same interneurones, it is not clear whether there is crosstalk between them. We utilized patch-clamp techniques to investigate this issue in rat hippocampal CA1 interneurones in slices under conditions where synaptic transmission was blocked. The alpha 7 nAChR-mediated currents were activated by choline, and when the activation of this receptor was preceded by the activation of the M-1 mAChR subtype, the amplitude of alpha 7 responses was significantly reduced in a rapidly reversible and voltage-independent manner, without any change in the kinetics of responses. This M-1 mAChR-mediated inhibition of alpha 7 nAChRs was through a PLC-, calcium- and PKC-dependent signal transduction cascade. These data show that M-1 mAChRs and alpha 7 nAChRs are functionally co-localized on individual rat hippocampal interneurones where the activation of these particular mAChRs inhibits alpha 7 nAChR function. This information will help to understand how these cholinergic receptor systems might be regulating neuronal excitability in the hippocampus in a manner that has relevance for synaptic plasticity and cognition.