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Spectrum: Autism Research News

Blinking mice bolster cerebellum’s link to autism

by  /  14 August 2015
Blink link: Researchers can gauge how well a mouse integrates sensory signals by tracking its blinking pattern.
THIS ARTICLE IS MORE THAN FIVE YEARS OLD

This article is more than five years old. Autism research — and science in general — is constantly evolving, so older articles may contain information or theories that have been reevaluated since their original publication date.

Mice carrying any one of five autism-linked mutations struggle to associate a flash of light with an irritating puff of air. The findings, published 9 July in Elife, suggest that the mice have trouble integrating information from multiple senses — a skill governed by the cerebellum1.

The cerebellum, a cauliflower-shaped region at the back of the brain, receives sensory information and translates it into action. Imaging and postmortem studies have found abnormalities in the cerebellum of people with autism, but how these relate to autism symptoms has been unclear.

The new findings suggest that the abnormalities spark some of the sensory difficulties associated with autism, says lead researcher Samuel Wang^, professor of molecular biology at Princeton University. Many people with autism have difficulty integrating information from multiple senses. The air puff test may model this sensory struggle, Wang says.

Wang and his team obtained mice with mutations in SHANK3 or MeCP2, the Rett syndrome gene. They also studied mice missing CNTNAP2 and those with an extra copy of the 15q11-13 chromosomal region. The fifth strain of mice lack the tuberous sclerosis gene, TSC1, in cerebellar neurons called Purkinje cells.

The researchers affixed a tiny magnet to the lower eyelid on each mouse and a detector on the upper eyelid to measure how quickly and fully each mouse blinked. They then showed each mouse a flash of green light, followed by a puff of air in its face.

Control mice learn to associate the light with the air puff, blinking in anticipation about half the time. By contrast, most of the mutant mice have difficulty making this connection. Mice missing TSC1 never learn to anticipate the puff of air, and the SHANK3, 15q duplication and CNTNAP2 mice anticipate it significantly less often than controls do.

Mice with mutant MeCP2 learn to blink, but their timing is off: They close their eyes too late and less fully than controls. SHANK3 and TSC1 mutant mice also close their eyes less than controls, but SHANK3 mice appear to blink a little too early.

These differences fall into two distinct categories: problems either with associating the flash of light with the puff of air, or with translating this information into action.

“The real importance of this study is that it suggests the severity and nature of the cerebellar alterations may vary across the different models,” says Matt Mosconi, assistant professor of psychiatry at the University of Texas, Southwestern in Dallas.

For example, SHANK3 and MeCP2 are expressed in granule cells — neurons in the cerebellum that receive sensory signals. So the findings suggest that granule cells are part of a circuit that controls the timing of blinks. TSC1, on the other hand, is expressed in Purkinje cells, which may belong to a circuit that helps to integrate sensory information.

Some people with autism also have trouble anticipating a puff of air2. Performing this test in young children may reveal problems with sensory integration before other autism symptoms appear, says Wang. “If you think about it, all early-life learning is multisensory,” he says. “What else do babies do other than link the taste of milk with mom’s voice?”


References:
  1. Kloth A.D. et al. Elife 4 PubMed
  2. Oristaglio J. et al. Neuroscience 248, 708-718 (2013) PubMed