Subcellular redistribution of m2 muscarinic acetylcholine receptors in striatal interneurons in vivo after acute cholinergic stimulation

• Type of Material: Article
• Authors: Veronique Bernard, Université Victor Ségalen-Bordeaux 2; Ouahiba Laribi, Université Victor Ségalen-Bordeaux 2; Allan I Levey, Emory University; Bertrand Bloch, Université Victor Ségalen-Bordeaux 2
• Language: English
• Date: 1998-12-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 1998 Society for Neuroscience
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.18-23-10207.1998
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 18
• Issue: 23
• Start Page: 10207
• End Page: 10218
• Grant/Funding Information: This work was supported in part by United States Public Health Service Grant RO1-NS30454.
• Keywords: SUBTYPE-SPECIFIC ANTIBODIES; Science & Technology; SUBSTANCE-P RECEPTOR; Neurosciences; basal ganglia; Neurosciences & Neurology; G-protein-coupled receptors; IMMUNOCYTOCHEMICAL LOCALIZATION; substance P receptor; SYNAPTIC LOCALIZATION; multivesicular bodies; AMPHETAMINE-TREATED RATS; Life Sciences & Biomedicine; BASAL FOREBRAIN; endocytosis; immunohistochemistry; IN-VIVO; FUNCTIONAL IMPLICATIONS; NEUROPEPTIDE MESSENGER-RNA; CORRELATED LIGHT
• Research Categories: Biology, Neuroscience

Abstract

The purpose of our work was to investigate how the cholinergic environment influences the targeting and the intracellular trafficking of the muscarinic receptor m2 (m2R) in vivo. To address this question, we have used immunohistochemical approaches at light and electron microscopic levels to detect the m2R in control rats and rats treated with muscarinic receptor agonists. In control animals, m2Rs were located mostly at postsynaptic sites at the plasma membrane of perikarya and dendrites of cholinergic and NPY- somatostatin interneurons as autoreceptors and heteroreceptors, respectively. Presynaptic receptors were also detected in boutons. The m2Rs were usually detected at extrasynaptic sites, but they could be found rarely in association with symmetrical synapses, suggesting that the cholinergic transmission mediated by m2R occurs via synaptic and nonsynaptic mechanisms. The stimulation of muscarinic receptors with oxotremorine provoked a dramatic alteration of m2R compartmentalization, including endocytosis with a decrease of the density of m2R at the membrane (-63%) and an increase of those associated with endosomes (+86%) in perikarya. The very strong increase of m2R associated with multivesicular bodies (+732%) suggests that oxotremorine activated degradation. The slight increase in the Golgi apparatus (+26%) suggests that the m2R stimulation had an effect on the maturation of m2R. The substance P receptor located at the membrane of the same neurons was unaffected by oxotremorine. Our data demonstrate that cholinergic stimulation dramatically influences the subcellular distribution of m2R in striatal interneurons in vivo. These events may have key roles in controlling abundance and availability of muscarinic receptors via regulation of receptor endocytosis, degradation, and/or neosynthesis. Further, the control of muscarinic receptor trafficking may influence the activity of striatal interneurons, including neurotransmitter release and/or electric activity.