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 M. Dorsa, Jeanne M. Wehner, G. Stanley McKnight, Rejean L. Idzerda

Research output: Contribution to journalArticle

125 Scopus citations

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
DOIs
StatePublished - May 15 1998

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Brandon, E. P., Logue, S. F., Adams, M. R., Qi, M., Sullivan, S. P., Matsumoto, A. M., Dorsa, D. M., Wehner, J. M., McKnight, G. S., & 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. https://doi.org/10.1523/jneurosci.18-10-03639.1998