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

doi:10.1038/sj.npp.1300309

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Sensorimotor Gating Deficits in Transgenic Mice Expressing a Constitutively Active Form of Gsα

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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 and Ted Abel

Neuropsychopharmacology (New York, N.Y.), Vol.29(3), pp.494-501

03/2004

DOI: 10.1038/sj.npp.1300309

PMCID: PMC3348581

PMID: 14694347

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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 CaMKII α promoter to drive expression in neurons within the forebrain, we have developed transgenic mice that express a constitutively active form of G s α (G s α *), the G protein that couples receptors such as the D 1 and D 5 dopamine receptors to adenylyl cyclase. We have also generated mice in which the CaMKII α 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 s α * and R(AB) transgenic mice. G s α * 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. G s α * 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.

startle response

G proteins

prepulse inhibition

schizophrenia

protein kinase A

animal model

Details

Title: Subtitle: Sensorimotor Gating Deficits in Transgenic Mice Expressing a Constitutively Active Form of Gsα
Creators: Thomas J Gould - Department of Psychology, Temple University, Weiss Hall, Philadelphia, PA, USA
Scott P Bizily - Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
Jan Tokarczyk - Division of Neuropsychiatry, University of Pennsylvania, Philadelphia, PA, USA
Michele P Kelly - Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
Steven J Siegel - Division of Neuropsychiatry, University of Pennsylvania, Philadelphia, PA, USA
Stephen J Kanes - Division of Neuropsychiatry, University of Pennsylvania, Philadelphia, PA, USA
Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
Resource Type: Journal article
Publication Details: Neuropsychopharmacology (New York, N.Y.), Vol.29(3), pp.494-501
DOI: 10.1038/sj.npp.1300309
PMID: 14694347
PMCID: PMC3348581
ISSN: 0893-133X
eISSN: 1740-634X
Grant note: T32 MH019112-10 || MH / National Institute of Mental Health : NIMH R01 MH060244-02 || MH / National Institute of Mental Health : NIMH P50 MH064045-01 || MH / National Institute of Mental Health : NIMH
Language: English
Date published: 03/2004
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065739002771

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