title: Exercise modifies α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor expression in striatopallidal neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse.
abstract: The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid-type glutamate receptor (AMPAR) plays a critical role in modulating experience-dependent neuroplasticity, and alterations in AMPAR expression may underlie synaptic dysfunction and disease pathophysiology. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of dopamine (DA) depletion, our previous work showed exercise increases total GluA2 subunit expression and the contribution of GluA2-containing channels in MPTP mice. The purpose of this study was to determine whether exercise-dependent changes in AMPAR expression after MPTP are specific to the striatopallidal (D2 R) or striatonigral (D1 R) medium spiny neuron (MSN) striatal projection pathways. Drd2 -eGFP-BAC transgenic mice were used to delineate differences in AMPAR expression between striatal D2 R-MSNs and D1 R-MSNs. Striatal AMPAR expression was assessed by immunohistochemical (IHC) staining, Western immunoblotting (WB) of preparations enriched for postsynaptic density (PSD), and alterations in the current-voltage relationship of MSNs. We found DA depletion results in the emergence of GluA2-lacking AMPARs selectively in striatopallidal D2 R-MSNs and that exercise reverses this effect in MPTP mice. Exercise-induced changes in AMPAR channels observed after DA depletion were associated with alterations in GluA1 and GluA2 subunit expression in postsynaptic protein, D2 R-MSN cell surface expression, and restoration of corticostriatal plasticity. Mechanisms regulating experience-dependent changes in AMPAR expression may provide innovative therapeutic targets to increase the efficacy of treatments for basal ganglia disorders, including Parkinson's disease.
authors.affiliation: The George and MaryLou Boone Center for Parkinson's Disease Research, Department of Neurology, University of Southern California, Los Angeles, California.
authors.forename: N
authors.initials: N
authors.lastname: Kintz
authors.forename: G M
authors.initials: GM
authors.lastname: Petzinger
authors.forename: G
authors.initials: G
authors.lastname: Akopian
authors.forename: S
authors.initials: S
authors.lastname: Ptasnik
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.forename: M W
authors.initials: MW
authors.lastname: Jakowec
authors.forename: J P
authors.initials: JP
authors.lastname: Walsh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010805:Physical Conditioning, Animal / Q000502:physiology*; D018091:Receptors, AMPA / Q000096:biosynthesis*
chemical_list: D018091:Receptors, AMPA
keywords: AMPA receptors; MPTP; Parkinson's disease; exercise; plasticity