title: Deletion of Gαq in the telencephalon alters specific neurobehavioral outcomes.
abstract: G(αq) -coupled receptors are ubiquitously expressed throughout the brain and body, and it has been shown that these receptors and associated signaling cascades are involved in a number of functional outputs, including motor function and learning and memory. Genetic alterations to G(αq) have been implicated in neurodevelopmental disorders such as Sturge-Weber syndrome. Some of these associated disease outcomes have been modeled in laboratory animals, but as G(αq) is expressed in all cell types, it is difficult to differentiate the underlying circuitry or causative neuronal population. To begin to address neuronal cell type diversity in G(αq) function, we utilized a conditional knockout mouse whereby G(αq) was eliminated from telencephalic glutamatergic neurons. Unlike the global G(αq) knockout mouse, we found that these conditional knockout mice were not physically different from control mice, nor did they exhibit any gross motor abnormalities. However, similarly to the constitutive knockout animal, G(αq) conditional knockout mice demonstrated apparent deficits in spatial working memory. Loss of G(αq) from glutamatergic neurons also produced enhanced sensitivity to cocaine-induced locomotion, suggesting that cortical G(αq) signaling may limit behavioral responses to psychostimulants. Screening for a variety of markers of forebrain neuronal architecture revealed no obvious differences in the conditional knockouts, suggesting that the loss of G(αq) in telencephalic excitatory neurons does not result in major alterations in brain structure or neuronal differentiation. Taken together, our results define specific modulation of spatial working memory and psychostimulant responses through disruptions in G(αq) signaling within cerebral cortical glutamatergic neurons.
authors.affiliation: Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, 32303.
authors.forename: Devon L
authors.initials: DL
authors.lastname: Graham
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Buendia
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Chapman
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Durai
authors.affiliation: Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, 32303.
authors.forename: Gregg D
authors.initials: GD
authors.lastname: Stanwood
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000172:deficiency* / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018765:Dopamine Uptake Inhibitors; D018698:Glutamic Acid; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D003042:Cocaine
keywords: Emx1; Gnaq; anxiety; conditional knockout; glutamate; locomotor activity; spatial working memory