A causative link between inner ear defects and long-term striatal dysfunction

Abstract

Psychiatric disorders frequently occur with inner ear dysfunction. Although socioenvironmental variables have been proposed as risk-factors, it is unclear, whether inner ear dysfunction can directly change brain function to promote abnormal behavior. Using Slc12a2 mutant mice, a model of inner ear dysfunction and Slc12a2 tissue-specific knockouts, we show that inner ear dysfunction induces a dopamine dependent increase in locomotor and repetitive motor activity by altering ventral neuro-striatal levels of pERK1/2, an intracellular mediator of striatal dopamine and glutamate signaling. Administration of the pERK1/2 inhibitor SL327 to the nucleus accumbens of the ventral striatum reverses this phenotype. Hence this study, in revealing a biological basis for the comorbidity of abnormal behavior and inner ear dysfunction, suggests that sensory impairment can contribute to psychiatric disorders traditionally considered exclusively of cerebral origin.