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

56 Citations (Scopus)

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

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Cues
Motor Activity
Neurons
Learning
Hyperkinesis
Corpus Striatum
G-Protein-Coupled Receptors
Reward
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Quintana, A., Sanz, E., Wang, W., Storey, G. P., Güler, A. D., Wanat, M. J., ... 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

Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors. / Quintana, Albert; Sanz, Elisenda; Wang, Wengang; Storey, Granville P.; Güler, Ali D.; Wanat, Matthew J.; Roller, Bryan A.; La Torre Vila, Anna; Amieux, Paul S.; McKnight, G. Stanley; Bamford, Nigel S.; Palmiter, Richard D.

In: Nature Neuroscience, Vol. 15, No. 11, 11.2012, p. 1547-1555.

Research output: Contribution to journalArticle

Quintana, A, Sanz, E, Wang, W, Storey, GP, Güler, AD, Wanat, MJ, Roller, BA, La Torre Vila, A, Amieux, PS, McKnight, GS, Bamford, NS & Palmiter, RD 2012, 'Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors', Nature Neuroscience, vol. 15, no. 11, pp. 1547-1555. https://doi.org/10.1038/nn.3239
Quintana, Albert ; Sanz, Elisenda ; Wang, Wengang ; Storey, Granville P. ; Güler, Ali D. ; Wanat, Matthew J. ; Roller, Bryan A. ; La Torre Vila, Anna ; Amieux, Paul S. ; McKnight, G. Stanley ; Bamford, Nigel S. ; Palmiter, Richard D. / Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors. In: Nature Neuroscience. 2012 ; Vol. 15, No. 11. pp. 1547-1555.
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