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

Michelle W. Antoine, Christian A. Hübner, Joseph C. Arezzo, Jean M. Hebert

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1120-1123
Number of pages4
JournalScience
Volume341
Issue number6150
DOIs
StatePublished - 2013

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Corpus Striatum
Inner Ear
Extracellular Signal-Regulated MAP Kinases
Hyperkinesis
Nucleus Accumbens
Brain
Response Elements
Adenosine
Neurotransmitter Agents
Carrier Proteins
Mutation

ASJC Scopus subject areas

  • General

Cite this

A causative link between inner ear defects and long-term striatal dysfunction. / Antoine, Michelle W.; Hübner, Christian A.; Arezzo, Joseph C.; Hebert, Jean M.

In: Science, Vol. 341, No. 6150, 2013, p. 1120-1123.

Research output: Contribution to journalArticle

Antoine, Michelle W. ; Hübner, Christian A. ; Arezzo, Joseph C. ; Hebert, Jean M. / A causative link between inner ear defects and long-term striatal dysfunction. In: Science. 2013 ; Vol. 341, No. 6150. pp. 1120-1123.
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