Neurobehavioral phenotyping of G(αq) knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair.
Many neurotransmitters, hormones, and sensory stimuli elicit their cellular responses through the targeted activation of receptors coupled to the G(αq) family of heterotrimeric G proteins. Nevertheless, we still understand little about the consequences of loss of this signaling activity on brain function. We therefore examined the effects of genetic inactivation of Gnaq, the gene that encode for G(αq), on responsiveness in a battery of behavioral tests in order to assess the contribution of G(αq) signaling capacity in the brain circuits mediating expression of affective behaviors (anxiety and behavioral despair), spatial working memory, and locomotor output (coordination, strength, spontaneous activity, and drug-induced responses). First, we replicated and extended findings showing clear motor deficits in G(αq) knockout mice as assessed on an accelerating rotarod and the inverted screen test. We then assessed the contribution of the basal ganglia motor loops to these impairments, using open field testing and analysis of drug-induced locomotor responses to the psychostimulant cocaine, the benzazepine D(1) receptor agonists SKF83822 and SKF83959, and the NMDA receptor antagonist MK-801. We observed significant increases in drug-induced locomotor activity in G(αq) knockout mice from the dopaminergic agonists but not MK-801, indicating that basal ganglia locomotor circuitry is largely intact in the absence of G(αq). Additionally, we observed normal phenotypes in both the elevated zero maze and the forced swim test indicating that anxiety and depression-related circuitry appears to be largely intact after loss of Gnaq expression. Lastly, use of the Y-maze revealed spatial memory deficits in G(αq) knockout mice, indicating that receptors signaling through G(αq) are necessary in these circuits for proficiency in this task.
Neuroscience Graduate Program, Vanderbilt University School of Medicine, Nashville TN, USA.
Aliya L
AL
Frederick
Tommy P
TP
Saborido
Gregg D
GD
Stanwood