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 studied 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 M-2 subtype of muscarinic receptor. It was unaffected by 6-cyano-7-nitroquinoxaline-2,3-dione (10 rho M), DL-2-amino-phosphonovaleric acid (30 mu M) and bicuculline (30 mu M). 5. Exogenous acetylcholine and muscarine also hyperpolarized the neurones, and this was blocked by methoctramine but not by pirenzepine, which is an M-1 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.