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A Gαs DREADD mouse for selective modulation of cAMP production in striatopallidal neurons.

Publication ,  Journal Article
Farrell, MS; Pei, Y; Wan, Y; Yadav, PN; Daigle, TL; Urban, DJ; Lee, H-M; Sciaky, N; Simmons, A; Nonneman, RJ; Huang, X-P; Hufeisen, SJ ...
Published in: Neuropsychopharmacology
April 2013

Here, we describe a newly generated transgenic mouse in which the Gs DREADD (rM3Ds), an engineered G protein-coupled receptor, is selectively expressed in striatopallidal medium spiny neurons (MSNs). We first show that in vitro, rM3Ds can couple to Gαolf and induce cAMP accumulation in cultured neurons and HEK-T cells. The rM3Ds was then selectively and stably expressed in striatopallidal neurons by creating a transgenic mouse in which an adenosine2A (adora2a) receptor-containing bacterial artificial chromosome was employed to drive rM3Ds expression. In the adora2A-rM3Ds mouse, activation of rM3Ds by clozapine-N-oxide (CNO) induces DARPP-32 phosphorylation, consistent with the known consequence of activation of endogenous striatal Gαs-coupled GPCRs. We then tested whether CNO administration would produce behavioral responses associated with striatopallidal Gs signaling and in this regard CNO dose-dependently decreases spontaneous locomotor activity and inhibits novelty induced locomotor activity. Last, we show that CNO prevented behavioral sensitization to amphetamine and increased AMPAR/NMDAR ratios in transgene-expressing neurons of the nucleus accumbens shell. These studies demonstrate the utility of adora2a-rM3Ds transgenic mice for the selective and noninvasive modulation of Gαs signaling in specific neuronal populations in vivo.This unique tool provides a new resource for elucidating the roles of striatopallidal MSN Gαs signaling in other neurobehavioral contexts.

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Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

April 2013

Volume

38

Issue

5

Start / End Page

854 / 862

Location

England

Related Subject Headings

  • Red Fluorescent Protein
  • Receptors, Muscarinic
  • Receptors, G-Protein-Coupled
  • Receptors, Dopamine D2
  • Receptors, Dopamine D1
  • Receptor, Adenosine A2A
  • Psychiatry
  • Phosphorylation
  • Neurons
  • Mice, Transgenic
 

Citation

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Chicago
ICMJE
MLA
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Farrell, M. S., Pei, Y., Wan, Y., Yadav, P. N., Daigle, T. L., Urban, D. J., … Roth, B. L. (2013). A Gαs DREADD mouse for selective modulation of cAMP production in striatopallidal neurons. Neuropsychopharmacology, 38(5), 854–862. https://doi.org/10.1038/npp.2012.251
Farrell, Martilias S., Ying Pei, Yehong Wan, Prem N. Yadav, Tanya L. Daigle, Daniel J. Urban, Hyeong-Min Lee, et al. “A Gαs DREADD mouse for selective modulation of cAMP production in striatopallidal neurons.Neuropsychopharmacology 38, no. 5 (April 2013): 854–62. https://doi.org/10.1038/npp.2012.251.
Farrell MS, Pei Y, Wan Y, Yadav PN, Daigle TL, Urban DJ, et al. A Gαs DREADD mouse for selective modulation of cAMP production in striatopallidal neurons. Neuropsychopharmacology. 2013 Apr;38(5):854–62.
Farrell, Martilias S., et al. “A Gαs DREADD mouse for selective modulation of cAMP production in striatopallidal neurons.Neuropsychopharmacology, vol. 38, no. 5, Apr. 2013, pp. 854–62. Pubmed, doi:10.1038/npp.2012.251.
Farrell MS, Pei Y, Wan Y, Yadav PN, Daigle TL, Urban DJ, Lee H-M, Sciaky N, Simmons A, Nonneman RJ, Huang X-P, Hufeisen SJ, Guettier J-M, Moy SS, Wess J, Caron MG, Calakos N, Roth BL. A Gαs DREADD mouse for selective modulation of cAMP production in striatopallidal neurons. Neuropsychopharmacology. 2013 Apr;38(5):854–862.

Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

April 2013

Volume

38

Issue

5

Start / End Page

854 / 862

Location

England

Related Subject Headings

  • Red Fluorescent Protein
  • Receptors, Muscarinic
  • Receptors, G-Protein-Coupled
  • Receptors, Dopamine D2
  • Receptors, Dopamine D1
  • Receptor, Adenosine A2A
  • Psychiatry
  • Phosphorylation
  • Neurons
  • Mice, Transgenic