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

• Published in: Neuroscience letters 2000-04, Vol.284 (3), p.182-186
• Main Authors: Rouse, ST, Edmunds, S M, Yi, H, Gilmor, M L, Levey, AI
• Format: Article
• Language: English
• ISSN: 0304-3940
• DOI: 10.1016/S0304-3940(00)01011-9

The muscarinic receptor family (M sub(1)-M sub(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 sub(2) receptor is described in detail for the pyramidal cell layer in the CAl region of the hippocampus. Electron microscopic analysis of M sub(2) immunoreactivity in this area revealed mainly presynaptic expression of this subtype. Double-labeling experiments using antibodies to M sub(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 sub(2) is located in cholinergic and non-cholinergic terminals. This is the first direct anatomical evidence that suggests that M sub(2) may indeed function as a cholinergic autoreceptor in the hippocampus. The distribution of the M sub(2) receptor in non-cholinergic terminals also suggests functional roles for M sub(2) as a presynaptic heteroreceptor.