Abstract
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 CAl 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 non-cholinergic terminals also suggests functional roles for M 2 as a presynaptic heteroreceptor.
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