A Causative Link Between Inner Ear Defects and Long-Term Striatal Dysfunction

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Science  06 Sep 2013:
Vol. 341, Issue 6150, pp. 1120-1123
DOI: 10.1126/science.1240405

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Deafness and Misbehavior

Behavioral problems accompanied by hyperactivity often occur in children with severe hearing loss and vestibular impairment. Explanations have focused on socioenvironmental factors, but Antoine et al. (p. 1120) found that inner ear defects can cause dysfunction in the striatum, which leads to abnormal behavior—especially hyperactivity—mediated by dopamine and glutamate signals, in an area of the striatum that is instrumental in controlling motor output. The abnormal behavior can be reversed by injection of an extracellular signal-regulated kinase inhibitor, which provides a novel target pathway for the treatment of behavioral disorders.


There is a high prevalence of behavioral disorders that feature hyperactivity in individuals with severe inner ear dysfunction. What remains unknown is whether inner ear dysfunction can alter the brain to promote pathological behavior. Using molecular and behavioral assessments of mice that carry null or tissue-specific mutations of Slc12a2, we found that inner ear dysfunction causes motor hyperactivity by increasing in the nucleus accumbens the levels of phosphorylated adenosine 3′,5′-monophosphate response element–binding protein (pCREB) and phosphorylated extracellular signal-regulated kinase (pERK), key mediators of neurotransmitter signaling and plasticity. Hyperactivity was remedied by local administration of the pERK inhibitor SL327. These findings reveal that a sensory impairment, such as inner ear dysfunction, can induce specific molecular changes in the brain that cause maladaptive behaviors, such as hyperactivity, that have been traditionally considered exclusively of cerebral origin.

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