Muscarinic receptor activity induces an afterdepolarization in a subpopulation of hippocampal CA1 interneurons

Cholinergic input to the hippocampus may be involved in important behaviora l functions and the pathophysiology of neurodegenerative diseases. Muscarin ic receptor activity in interneurons of the hippocampus may play a role in these actions. In this study, we investigated the effects of muscarinic rec eptor activity on the excitability of different subtypes of interneurons in rat hippocampal CA1. Most interneurons displayed an afterhyperpolarizing p otential (AHP) after depolarization by injected current or synaptic stimula tion. In the presence of a muscarinic agonist, the AHP of a subset of these interneurons was replaced by an afterdepolarization (ADP), often of suffic ient magnitude to evoke action potentials in the absence of further stimula tion. The ADP was insensitive to cadmium and low extracellular calcium. It was blocked by low extracellular sodium but not by tetrodotoxin or low conc entrations of amiloride. Muscarinic ADPs were sometimes observed in isolati on but were often accompanied by depolarizing, hyperpolarizing, or biphasic changes in the membrane potential. Interneurons with muscarinic ADPs were found in all strata of CA1 and did not fall into a single morphological cla ssification. The potential functions of the prolonged action potential outp ut of interneurons produced by the ADP could include changes in hippocampal circuit properties and facilitation of the release of peptide cotransmitte rs in these interneurons.