Subcellular distribution of M2 muscarinic receptors in relation to dopaminergic neurons of the rat ventral tegmental area
- 22 August 2006
- journal article
- research article
- Published by Wiley in Journal of Comparative Neurology
- Vol. 498 (6), 821-839
- https://doi.org/10.1002/cne.21082
Abstract
Acetylcholine can affect cognitive functions and reward, in part, through activation of muscarinic receptors in the ventral tegmental area (VTA) to evoke changes in mesocorticolimbic dopaminergic transmission. Among the known muscarinic receptor subtypes present in the VTA, the M2 receptor (M2R) is most implicated in autoregulation and also may play a heteroreceptor role in regulation of the output of the dopaminergic neurons. We sought to determine the functionally relevant sites for M2R activation in relation to VTA dopaminergic neurons by examining the electron microscopic immunolabeling of M2R and the dopamine transporter (DAT) in the VTA of rat brain. The M2R was localized to endomembranes in DAT‐containing somatodendritic profiles but showed a more prominent, size‐dependent plasmalemmal location in nondopaminergic dendrites. M2R also was located on the plasma membrane of morphologically heterogenous axon terminals contacting unlabeled as well as M2R‐ or DAT‐labeled dendrites. Some of these terminals formed asymmetric synapses resembling those of cholinergic terminals in the VTA. The majority, however, formed symmetric, inhibitory‐type synapses or were apposed without recognized junctions. Our results provide the first ultrastructural evidence that the M2R is expressed, but largely not available for local activation, on the plasma membrane of VTA dopaminergic neurons. Instead, the M2R in this region has a distribution suggesting more indirect regulation of mesocorticolimbic transmission through autoregulation of acetylcholine release and changes in the physiological activity or release of other, largely inhibitory transmitters. These findings could have implications for understanding the muscarinic control of cognitive and goal‐directed behaviors within the VTA. J. Comp. Neurol. 498:821–839, 2006.Keywords
This publication has 112 references indexed in Scilit:
- Muscarinic receptor subtypes mediating central and peripheral antinociception studied with muscarinic receptor knockout miceLife Sciences, 2003
- Muscarinic receptor M2 in cat visual cortex: Laminar distribution, relationship to γ‐aminobutyric acidergic neurons, and effect of cingulate lesionsJournal of Comparative Neurology, 2001
- Major coexpression of κ‐opioid receptors and the dopamine transporter in nucleus accumbens axonal profilesSynapse, 2001
- Localization of the m2 muscarinic acetylcholine receptor protein and mRNA in cortical neurons of the normal and cholinergically deafferented rhesus monkeyJournal of Comparative Neurology, 1998
- Mechanisms of modulation of voltage‐dependent calcium channels by G proteinsThe Journal of Physiology, 1998
- Muscarinic acetylcholine receptor subtype, m2: Diverse functional implications of differential synaptic localizationLife Sciences, 1997
- Extrasynaptic Glutamate Spillover in the Hippocampus: Dependence on Temperature and the Role of Active Glutamate UptakeNeuron, 1997
- Ultrastructural relationships between terminals immunoreactive for enkephalin, GABA, or both transmitters in the rat ventral tegmental areaBrain Research, 1995
- Muscarinic Receptor SubtypesAnnual Review of Pharmacology and Toxicology, 1990
- Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures.Journal of Histochemistry & Cytochemistry, 1981