Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors

Albert Quintana, Elisenda Sanz, Wengang Wang, Granville P. Storey, Ali D. Güler, Matthew J. Wanat, Bryan A. Roller, Anna La Torre Vila, Paul S. Amieux, G. Stanley McKnight, Nigel S. Bamford, Richard D. Palmiter

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear. We found that, in the absence of GPR88, MSNs showed increased glutamatergic excitation and reduced GABAergic inhibition, which promoted enhanced firing rates in vivo, resulting in hyperactivity, poor motor coordination and impaired cue-based learning in mice. Targeted viral expression of GPR88 in MSNs rescued the molecular and electrophysiological properties and normalized behavior, suggesting that aberrant MSN activation in the absence of GPR88 underlies behavioral deficits and its dysfunction may contribute to behaviors observed in neuropsychiatric disease.

Original languageEnglish (US)
Pages (from-to)1547-1555
Number of pages9
JournalNature Neuroscience
Volume15
Issue number11
DOIs
StatePublished - Nov 2012
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Quintana, A., Sanz, E., Wang, W., Storey, G. P., Güler, A. D., Wanat, M. J., Roller, B. A., La Torre Vila, A., Amieux, P. S., McKnight, G. S., Bamford, N. S., & Palmiter, R. D. (2012). Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors. Nature Neuroscience, 15(11), 1547-1555. https://doi.org/10.1038/nn.3239