Defective motor behavior and neural gene expression in RIIβ-protein kinase A mutant mice

Eugene P. Brandon, Sheree F. Logue, Monique R. Adams, Ming Qi, Sean P. Sullivan, Alvin M. Matsumoto, Daniel Dorsa, Jeanne M. Wehner, G. Stanley McKnight, Rejean L. Idzerda

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Motor behavior is modulated by dopamine-responsive neurons in the striatum, where dopaminergic signaling uses G-protein-coupled pathways, including those that result in the activation of cAMP-dependent protein kinase (PKA). The RIIβ isoform of PKA is highly enriched in the striatum, and targeted disruption of the RIIβ gene in mice leads to a dramatic reduction in total PKA activity in this region. Although the mutant mice show typical locomotor responses after acute administration of dopaminergic drugs, they display abnormalities in two experience-dependent locomotor behaviors: training on the rotarod task and locomotor sensitization to amphetamine. In addition, amphetamine induction of fos is absent, and the basal expression of dynorphin mRNA is reduced in the striatum. These results demonstrate that motor learning and the regulation of neuronal gene expression require RIIβ PKA, whereas the acute locomotor effects of dopaminergic drugs are relatively unaffected by this PKA deficiency.

Original languageEnglish (US)
Pages (from-to)3639-3649
Number of pages11
JournalJournal of Neuroscience
Volume18
Issue number10
StatePublished - May 15 1998
Externally publishedYes

Fingerprint

Cyclic AMP-Dependent Protein Kinases
Protein Kinases
Gene Expression
Dopamine Agents
Amphetamine
Dynorphins
Protein Deficiency
Dopaminergic Neurons
Gene Expression Regulation
GTP-Binding Proteins
Protein Isoforms
Learning
Messenger RNA
Genes

Keywords

  • Amphetamine
  • cAMP-dependent protein kinase
  • Dopamine
  • Dynorphin
  • Fos
  • Knockout
  • Locomotion
  • Mouse
  • PKA
  • Rotarod
  • Se nsitization
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Brandon, E. P., Logue, S. F., Adams, M. R., Qi, M., Sullivan, S. P., Matsumoto, A. M., ... Idzerda, R. L. (1998). Defective motor behavior and neural gene expression in RIIβ-protein kinase A mutant mice. Journal of Neuroscience, 18(10), 3639-3649.

Defective motor behavior and neural gene expression in RIIβ-protein kinase A mutant mice. / Brandon, Eugene P.; Logue, Sheree F.; Adams, Monique R.; Qi, Ming; Sullivan, Sean P.; Matsumoto, Alvin M.; Dorsa, Daniel; Wehner, Jeanne M.; McKnight, G. Stanley; Idzerda, Rejean L.

In: Journal of Neuroscience, Vol. 18, No. 10, 15.05.1998, p. 3639-3649.

Research output: Contribution to journalArticle

Brandon, EP, Logue, SF, Adams, MR, Qi, M, Sullivan, SP, Matsumoto, AM, Dorsa, D, Wehner, JM, McKnight, GS & Idzerda, RL 1998, 'Defective motor behavior and neural gene expression in RIIβ-protein kinase A mutant mice', Journal of Neuroscience, vol. 18, no. 10, pp. 3639-3649.
Brandon EP, Logue SF, Adams MR, Qi M, Sullivan SP, Matsumoto AM et al. Defective motor behavior and neural gene expression in RIIβ-protein kinase A mutant mice. Journal of Neuroscience. 1998 May 15;18(10):3639-3649.
Brandon, Eugene P. ; Logue, Sheree F. ; Adams, Monique R. ; Qi, Ming ; Sullivan, Sean P. ; Matsumoto, Alvin M. ; Dorsa, Daniel ; Wehner, Jeanne M. ; McKnight, G. Stanley ; Idzerda, Rejean L. / Defective motor behavior and neural gene expression in RIIβ-protein kinase A mutant mice. In: Journal of Neuroscience. 1998 ; Vol. 18, No. 10. pp. 3639-3649.
@article{90b6b73ec4bd45c28c02528485376350,
title = "Defective motor behavior and neural gene expression in RIIβ-protein kinase A mutant mice",
abstract = "Motor behavior is modulated by dopamine-responsive neurons in the striatum, where dopaminergic signaling uses G-protein-coupled pathways, including those that result in the activation of cAMP-dependent protein kinase (PKA). The RIIβ isoform of PKA is highly enriched in the striatum, and targeted disruption of the RIIβ gene in mice leads to a dramatic reduction in total PKA activity in this region. Although the mutant mice show typical locomotor responses after acute administration of dopaminergic drugs, they display abnormalities in two experience-dependent locomotor behaviors: training on the rotarod task and locomotor sensitization to amphetamine. In addition, amphetamine induction of fos is absent, and the basal expression of dynorphin mRNA is reduced in the striatum. These results demonstrate that motor learning and the regulation of neuronal gene expression require RIIβ PKA, whereas the acute locomotor effects of dopaminergic drugs are relatively unaffected by this PKA deficiency.",
keywords = "Amphetamine, cAMP-dependent protein kinase, Dopamine, Dynorphin, Fos, Knockout, Locomotion, Mouse, PKA, Rotarod, Se nsitization, Striatum",
author = "Brandon, {Eugene P.} and Logue, {Sheree F.} and Adams, {Monique R.} and Ming Qi and Sullivan, {Sean P.} and Matsumoto, {Alvin M.} and Daniel Dorsa and Wehner, {Jeanne M.} and McKnight, {G. Stanley} and Idzerda, {Rejean L.}",
year = "1998",
month = "5",
day = "15",
language = "English (US)",
volume = "18",
pages = "3639--3649",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "10",

}

TY - JOUR

T1 - Defective motor behavior and neural gene expression in RIIβ-protein kinase A mutant mice

AU - Brandon, Eugene P.

AU - Logue, Sheree F.

AU - Adams, Monique R.

AU - Qi, Ming

AU - Sullivan, Sean P.

AU - Matsumoto, Alvin M.

AU - Dorsa, Daniel

AU - Wehner, Jeanne M.

AU - McKnight, G. Stanley

AU - Idzerda, Rejean L.

PY - 1998/5/15

Y1 - 1998/5/15

N2 - Motor behavior is modulated by dopamine-responsive neurons in the striatum, where dopaminergic signaling uses G-protein-coupled pathways, including those that result in the activation of cAMP-dependent protein kinase (PKA). The RIIβ isoform of PKA is highly enriched in the striatum, and targeted disruption of the RIIβ gene in mice leads to a dramatic reduction in total PKA activity in this region. Although the mutant mice show typical locomotor responses after acute administration of dopaminergic drugs, they display abnormalities in two experience-dependent locomotor behaviors: training on the rotarod task and locomotor sensitization to amphetamine. In addition, amphetamine induction of fos is absent, and the basal expression of dynorphin mRNA is reduced in the striatum. These results demonstrate that motor learning and the regulation of neuronal gene expression require RIIβ PKA, whereas the acute locomotor effects of dopaminergic drugs are relatively unaffected by this PKA deficiency.

AB - Motor behavior is modulated by dopamine-responsive neurons in the striatum, where dopaminergic signaling uses G-protein-coupled pathways, including those that result in the activation of cAMP-dependent protein kinase (PKA). The RIIβ isoform of PKA is highly enriched in the striatum, and targeted disruption of the RIIβ gene in mice leads to a dramatic reduction in total PKA activity in this region. Although the mutant mice show typical locomotor responses after acute administration of dopaminergic drugs, they display abnormalities in two experience-dependent locomotor behaviors: training on the rotarod task and locomotor sensitization to amphetamine. In addition, amphetamine induction of fos is absent, and the basal expression of dynorphin mRNA is reduced in the striatum. These results demonstrate that motor learning and the regulation of neuronal gene expression require RIIβ PKA, whereas the acute locomotor effects of dopaminergic drugs are relatively unaffected by this PKA deficiency.

KW - Amphetamine

KW - cAMP-dependent protein kinase

KW - Dopamine

KW - Dynorphin

KW - Fos

KW - Knockout

KW - Locomotion

KW - Mouse

KW - PKA

KW - Rotarod

KW - Se nsitization

KW - Striatum

UR - http://www.scopus.com/inward/record.url?scp=0032525114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032525114&partnerID=8YFLogxK

M3 - Article

C2 - 9570795

AN - SCOPUS:0032525114

VL - 18

SP - 3639

EP - 3649

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 10

ER -