Hyperactivity can be a frustrating experience for children as well as for their parents, teachers and other caregivers. The state typically is viewed simply as abnormal behavior, with little understanding of its causes. Now, research with mice points to an unlikely source: a defective inner ear. The physiological link between hyperactivity and the inner ear lies within a mutation in a gene called Slc12a2. Normally, the gene encodes an SLC12A2 protein important in maintaining proper ionic balance and cell volume. This protein is broadly expressed in tissues, including in the central nervous system (CNS) and the inner ear. The mechanism behind the biological link occurs when Slc12a2 holds a specific mutation that turns a codon (a genetic sequence) for potassium lysine into a stop codon (which terminates protein production). Researchers at Albert Einstein College of Medicine in New York City found that when this mutation took place there was a loss of detectable SLC12A2 protein. Its deficit in the inner ear resulted in a collapse of Reissner’s membrane inside the cochlea as well as additional membranes in the inner ear’s vestibular compartments (which deal with balance and spatial orientation). They were surprised to find, however, that when the mutation occurred in the genes within the particular brain regions such as the cortex, striatum (forebrain), cerebellum or throughout the CNS, neither abnormal behavior nor inner ear dysfunction resulted. Michelle Antoine, then a neuroscience PhD student, suspected a physiological link when she noticed a set of mice in geneticist Jean Hébert’s lab behaving abnormally—chasing their tails and almost always moving. After analyzing the mice’s CNS and peripheral nervous systems, she found that the animals’ inner ears were defective and their brains exhibited some abnormalities. She realized the mice provided an opportunity to study the association between ear defects and abnormal behavior. Hébert hopes that the finding could shift the focus of hyperactivity treatment from altering simple behavior to biology. Still, he thinks further research must be done before the gap can be bridged between treating mice and treating humans. Questions that remain unaddressed include the severity of the ear dysfunction and its timing. “We also don’t know whether the hyperactivity lies primarily in the auditory portion of the ear or the vestibular component,” Hébert says. Coming up with answers may prove difficult. Researchers currently know little about the way in which auditory and vestibular input affect the striatum, but Hébert and his team are pursuing these answers. “I think this project could have a big impact in solving the fundamental question of how hyperactivity could be treated in the many children born with chronic vestibular and auditory dysfunctions,” Harvard Medical School otologist and neurobiologist Ruth Anne Eatock says. The research has provided a mechanism for the mutation, and thus a target for drug treatment. Follow Scientific American on Twitter @SciAm and @SciamBlogs. Visit ScientificAmerican.com for the latest in science, health and technology news.
© 2013 ScientificAmerican.com. All rights reserved.