GPR88 signatures in mouse neuronal connectivity and behavior : a potential therapeutic target for psychiatric disorders

Pathological agitations of the brain and the expression or mutation of single gene affect overall brain connectivity. Here we combined mouse mutagenesis with functional and structural MRI and explored mouse whole brain connectivity maps non-invasively in response to the inactivation of Gpr88 gene. We perceived robust modifications in the default mode network which is considered a hallmark of many psychiatric conditions, followed by sensori-motor network allied to sensorimotor gating deficiency underlying hyperactivity phenotype in Gpr88-/- mice. In addition, hippocampal and dorsal striatum functional connectivity perturbations might underlie learning deficiency and weakened amygdala connectivity with cortex and striatum might suggest triggering of risk-taking behavior previously observed in these animals. Moreover, Gpr88 deletion strongly modifies the reward network leading Gpr88-/- mice vulnerable to alcohol intake. This is the first evidence of Gpr88 involvement in reshaping the mouse brain connectome. The concordance between connectivity alterations and behavior deficits posits Gpr88 as a potential target for psychiatric disorders.