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The Journal of Neuroscience, December 1, 1998, 18(23):10207-10218
Subcellular Redistribution of m2 Muscarinic Acetylcholine
Receptors in Striatal Interneurons In Vivo after Acute
Cholinergic Stimulation
Véronique
Bernard1,
Ouahiba
Laribi1,
Allan I.
Levey2, and
Bertrand
Bloch1
1 Centre National de la Recherche Scientifique,
Unité Mixte de Recherche 5541, Laboratoire
d'Histologie-Embryologie, Université Victor
Ségalen-Bordeaux 2, 33076 Bordeaux cedex, France, and
2 Emory University, Atlanta, Georgia 30322
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.
Key words:
endocytosis; G-protein-coupled receptors; substance P
receptor; basal ganglia; immunohistochemistry; multivesicular
bodies
Copyright © 1998 Society for Neuroscience 0270-6474/98/182310207-12$05.00/0
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