Elsevier

Neuroscience Letters

Volume 284, Issue 3, 28 April 2000, Pages 182-186
Neuroscience Letters

Localization of M2 muscarinic acetylcholine receptor protein in cholinergic and non-cholinergic terminals in rat hippocampus

https://doi.org/10.1016/S0304-3940(00)01011-9Get rights and content

Abstract

The muscarinic receptor family (M1–M4) 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 M2 receptor is described in detail for the pyramidal cell layer in the CAl region of the hippocampus. Electron microscopic analysis of M2 immunoreactivity in this area revealed mainly presynaptic expression of this subtype. Double-labeling experiments using antibodies to M2 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 M2 is located in cholinergic and non-cholinergic terminals. This is the first direct anatomical evidence that suggests that M2 may indeed function as a cholinergic autoreceptor in the hippocampus. The distribution of the M2 receptor in non-cholinergic terminals also suggests functional roles for M2 as a presynaptic heteroreceptor.

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Acknowledgements

This study was supported by RO1 N530454 (A.I.L.). S.T.R. and M.L.G. were recipients of pre-doctoral National Research Service Awards from the NIMH (F31 MH11186-02, S.T.R.; F31 MH11474-01, M.L.G.). We would like to acknowledge Dr Howard Rees for expert technical assistance.

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