Muscarinic IPSPs in rat striatal cholinergic interneurones

1. Intracellular recordings were made from neurones in slices of rat striatum in vitro. 2. The forty-nine neurones studies were immunoreactive for choline acetyltransferase and had the electrophysiological characteristics typical of large aspiny interneurones. 3. Focal stimulation of the slice elicited a hyperpolarizing inhibitory postsynaptic potential in thirty-five neurones. This IPSP lasted 0.5-1 s and reversed polarity at a membrane potential which was dependent on the logarithm of the extracellular potassium concentration. 4. The IPSP was reversibly blocked by scopolamine and methoctramine, which has some selectivity for the M₂ subtype of muscarinic receptor. It was unaffected by 6-cyano-7-nitroquinoxaline-2,3-dione (10 μM), DL-2-amino-phosphonovaleric acid (30 μM) and bicuculline (30 μM). 5. Exogenous acetylcholine and muscarine also hyperpolarized the neurones, and this was blocked by methoctramine but not by pirenzepine, which is an M₁ receptor-selective antagonist. 6. The findings demonstrate that muscarinic IPSPs occur in the central nervous system. The IPSP may mediate an 'autoinhibition' of striatal cholinergic neurone activity.