自闭症之突变基因影响大脑听觉区域

New research from Cold Spring Harbor Laboratory (CSHL) might help explain how a gene¹ mutation² found in some autistic individuals leads to difficulties in processing auditory cues and paying spatial³（空间的） attention to sound. The study has found that when a suspected autism gene called PTEN is deleted from auditory cortical neurons -- the main workhorses of the brain's sound-processing center -- the signals that these neurons receive from local as well as long-distance sources are strengthened beyond normal levels. These effects, the study shows, can be blocked by a drug currently in use as an immunosuppressant.

"It's long been hypothesized that autism spectrum⁴ disorders⁵ (ASDs) arise from a partial disruption of long-range connections in the brain during development," explains Professor Tony Zador, who led the study. "Our finding that PTEN-deficient neurons receive stronger inputs⁶ suggests that one way this disruption can be caused is by signal enhancement." His team's work appears in the Journal of Neuroscience on February 1.

Although ASDs could arise from mutations in any of dozens of candidate genes⁷, a core triad（三个一组） of symptoms defines all cases: impaired⁸ language, impaired social interaction, and restricted and repetitive behaviors. "The challenge therefore has been to understand how this diverse set of candidate genes and the pathways they control converge⁹ to cause the common signature of ASDs," Zador says.

The auditory cortex, which plays a critical role in auditory attention and perception, forms functional¹⁰ connections with other sensory¹¹ cortices and critical brain areas. The neural¹² network within the auditory cortex has therefore been a target of studies aimed at understanding how alterations¹³ in neural circuits contribute to dysfunction in ASDs.

Zador's team focused for several reasons on the role of one suspected autism candidate gene, PTEN, on circuit alterations within the auditory cortex. Well known for its role as an anti-cancer gene that powers down cell growth, proliferation and survival, this gene has also been linked to ASDs by a slew¹⁴ of studies in humans and mice. PTEN mutations have been found in autistic individuals with extreme macroencephaly（巨脑） -- an increase in brain volume. PTEN loss in mice has been found to boost cell size and the number of neuronal connections in the brain.