Localization of M-2 muscarinic acetylcholine receptor protein in cholinergic and non-cholinergic terminals in rat hippocampus

The muscarinic receptor family (M-1-M-4) mediates cholinergic modulation of hippocampal transmission. Pharmacological and physiological studies have i ndicated that a presynaptic receptor on cholinergic terminals plays a key r ole in regulating ACh release, although the molecular identity of this subt ype is uncertain, In this study, the localization of the M-2 receptor is de scribed in detail for the pyramidal cell layer in the CAI region of the hip pocampus. Electron microscopic analysis of M-2 immunoreactivity in this are a revealed mainly presynaptic expression of this subtype. Double-labeling e xperiments using antibodies to M-2 and to the vesicular acetylcholine trans porter, a novel, specific marker of cholinergic terminals, were used to inv estigate the nature of these presynaptic receptors. These studies have reve aled that M-2 is located in cholinergic and non-cholinergic terminals. This is the first direct anatomical evidence that suggests that M-2 may indeed function as a cholinergic autoreceptor in the hippocampus. The distribution of the M-2 receptor in noncholinergic terminals also suggests functional r oles for Mp as a presynaptic heteroreceptor. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.