Distinct Roles of GluA2-lacking AMPA Receptor Expression in Dopamine D1 or D2 Receptor Neurons in Animal Behavior. (1st February 2019)

• Record Type: Journal Article
• Authors: Shou, Jiayi; Tran, Angelica; Snyder, Natasha; Bleem, Eric; Kim, Seonil
• Is Part Of: Neuroscience. Volume 398(2019)
• Page Start: 102
• Page End: 112
• Publication Date: 2019-02-01
• Subjects: calcium-permeable AMPA receptor -- D1 receptor -- D2 receptor -- animal behavior; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.12.002
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Neurons expressing dopamine receptors, D1 or D2 receptors (D1Rs or D2Rs) have distinct behavioral effects. GluA2-lacking AMPA receptor expression in these two subpopulations differentially affects animal behavior. GluA2-lacking AMPA receptor expression plays crucial roles in dopaminergic circuit-mediated animal behavior. Abstract: Dopaminergic signaling in the central nervous system regulates several aspects of animal behavior. In the dopaminergic circuits, there are two classes of neurons that can be differentiated by their expression of dopamine receptors, D1 or D2 receptors (D1Rs or D2Rs). Notably, Ca 2+ -permeable GluA2-lacking glutamate AMPA receptors (CP-AMPARs) are important for gating synaptic plasticity and gene expression in neurons, and their expression particularly in the striatum affects various forms of animal behavior. However, differential effects of GluA2-lacking AMPARs in D1R or D2R neurons on animal behavior have not been addressed. Here, we employed the Cre-Lox recombination system to remove GluA2 selectively in D1R or D2R neurons to express CP-AMPARs and carried out multiple behavior assays. First, the open-field assay revealed that D2R GluA2 knockout (KO) mice showed hypoactivity, while GluA2 KO in D1R neurons had no effect on locomotor activity. We also revealed that D1R GluA2 KO mice showed delayed learning in the accelerating rotarod test compared with control animals, whereas D2R GluA2 KO animals exhibited complete loss of motor learning. In the sociability test, GluA2-lacking AMPAR expression in D1R neurons induced hypersociability, whereas D2R GluA2 KO mice elicited loss of sociability. Both D1R and D2R GluA2 KO mice consumed less food compared with control animals, while D1R GluA2 KO animals showed significantly more weight gain. Finally, D1R GluA2 KO induced anti-depressant effects, while GluA2-lacking AMPAR expression in D2R neurons promoted depression-like behavior. Taken together, GluA2-lacking CP-AMPAR expression in D1R and D2R neurons differentially affects animal behavior.