Loss of language gene enhances pitch discrimination in mice

Mice lacking the autism-linked gene CNTNAP2 process sounds more slowly than control mice do but are better at discriminating between tones. The unpublished research was presented Tuesday at the 2013 Society for Neuroscience annual meeting in San Diego.

Mutations in CNTNAP2 are strongly linked to specific language impairment, a disorder in which language difficulties are not accompanied by social or intellectual deficits. The gene has also been implicated in autism.

In the new study, researchers measured how sound cues affect the startle reflex in mice lacking CNTNAP2. The test begins with a mouse placed on a platform. A loud burst of sound plays, startling the mouse and causing it to push down on the platform. The amount of force on the platform reflects how startled the mouse is.

Before some bursts of sound, the researchers give the mice another sound-related cue indicating that the loud noise is imminent. “If the mouse is able to detect the cue before the burst, it won’t be startled,” explains Amanda Rendall, a graduate student in R. Holly Fitch’s lab at the University of Connecticut who presented the work.

The researchers calculated how much a mouse’s startle response diminishes with the cue relative to without. The decrease reflects its auditory processing abilities.

The researchers performed two versions of the startle test. In the first, the cue is a period of silence that interrupts background white noise. Mice that lack CNTNAP2 do worse on this test than controls. In people, poor performance on this test has been shown to reflect delays in sound processing.

In the other version of the test, the researchers play one tone constantly in the background, and the cue is a low tone layered on that background. In this test, the mutant mice outperform controls, indicating that they are better at discriminating pitch.

“We’ve never seen this flip before,” says Rendall. Other mouse models of autism that have shown auditory processing deficits show consistent impairment across different tests, she says.

People with autism have also been reported to have auditory processing delays, and there is some evidence that they are better at detecting differences in pitch than controls are.

The new study’s findings indicate that the mice in the study also “have both a deficit and an enhancement, so that makes it interesting,” says Stephanie White, professor of integrative biology and physiology at the University of California, Los Angeles, who was not involved in the work. “It’s eerily parallel to the reported auditory deficits of autistic individuals.”

It’s not yet clear what role this enhanced pitch discrimination plays in language deficits in autism. “It may be related to overprocessing of auditory information,” Rendall says.

For more reports from the 2013 Society for Neuroscience annual meeting, please click here.