Localization of M2 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 indicated that a presynaptic receptor on cholinergic terminals plays a key role in regulating ACh release, although the molecular identity of this subtype is uncertain, In this study, the localization of the M-2 receptor is described in detail for the pyramidal cell layer in the CAI region of the hippocampus. Electron microscopic analysis of M-2 immunoreactivity in this area revealed mainly presynaptic expression of this subtype. Double-labeling experiments using antibodies to M-2 and to the vesicular acetylcholine transporter, a novel, specific marker of cholinergic terminals, were used to investigate the nature of these presynaptic receptors. These studies have revealed 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 roles for Mp as a presynaptic heteroreceptor. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.