Sensorimotor gating deficits in transgenic mice expressing a constitutively active form of Gsα

Thomas J. Gould, Scott P. Bizily, Jan Tokarczyk, Michele P. Kelly, Steven J. Siegel, Stephen J. Kanes, Ted Abel

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Abstract

Schizophrenia is a complex disorder characterized by wide-ranging cognitive impairments, including deficits in learning as well as sensory gating. The causes of schizophrenia are unknown, but alterations in intracellular G-protein signaling pathways are among the molecular changes documented in patients with schizophrenia. Using the CaMKIIα promoter to drive expression in neurons within the forebrain, we have developed transgenic mice that express a constitutively active form of Gsα (G sα*), the G protein that couples receptors such as the D1 and D5 dopamine receptors to adenylyl cyclase. We have also generated mice in which the CaMKIIα promoter drives expression of a dominant-negative form of protein kinase A, R(AB). Here, we examine startle responses and prepulse inhibition of the startle reflex (PPI) in these G sα* and R(AB) transgenic mice. Gsα* transgenic mice exhibited selective deficits in PPI, without exhibiting alterations in the startle response, whereas no deficit in startle or PPI was found in the R(AB) transgenic mice. Thus, overstimulation of the cAMP/PKA pathway disrupts PPI, but the cAMP/PKA pathway may not be essential for sensorimotor gating. Gsα* transgenic mice may provide an animal model of certain endophenotypes of schizophrenia, because of the similarities between them and patients with schizophrenia in G-protein function, hippocampus-dependent learning, and sensorimotor gating.

Original languageEnglish (US)
Pages (from-to)494-501
Number of pages8
JournalNeuropsychopharmacology
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 1 2004

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Gould, T. J., Bizily, S. P., Tokarczyk, J., Kelly, M. P., Siegel, S. J., Kanes, S. J., & Abel, T. (2004). Sensorimotor gating deficits in transgenic mice expressing a constitutively active form of Gsα. Neuropsychopharmacology, 29(3), 494-501. https://doi.org/10.1038/sj.npp.1300309