Deletion of Gαq in the telencephalon alters specific neurobehavioral outcomes

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. Synapse 69:434–445, 2015. © 2015 Wiley Periodicals, Inc.