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Autism and the insula: genomic and neural circuits

John Allman, Ph.D.
California Institute of Technology


People with autism spectrum disorders often lack self-awareness, making it difficult for them to interact and empathize with others. Using new genomics methods to study the neurons that are active during self-awareness and empathy, John Allman and Barbara Wold of the California Institute of Technology are learning how these processes are different in people with autism.

Empathy is the physiological mirroring of another’s feelings by observing that individual. For example, when another person is in pain, the observer’s peripheral neurons are activated, creating a similar feeling in his or her own body. Empathy also activates a brain region known as the anterior insular cortex, which is active when people are self-aware, such as when they describe their feelings. Indeed, individuals with autism tend not to have strong physiological reactions in either their muscles or in the anterior insular cortex when they observe others in pain. The ventral part of anterior insular cortex, the fronto-insular cortex, contains a group of neurons known as the Von Economo neurons, which Allman and Wold hypothesize are involved in self-monitoring and self-regulation.

The researchers are using a technique recently developed in the Wold lab, called RNA-Seq, to study gene expression in the anterior insular cortex of the brains of individuals with autism. In RNA-Seq, messenger RNA is extracted from tissues and analyzed with high-throughput sequencing technologies. This technique can be used to quickly identify all of the expressed genes in a tissue, and it provides information on the strength of expression as well. In the researchers’ pilot study, RNA-Seq data revealed the abnormal expression of genes involved in inflammation and neuronal function.

Allman and Wold are using laser microdissection to isolate specific cell types within the fronto-insular cortex — including the Von Economo neurons — for RNA-Seq analysis, which may allow them to detect gene expression that would otherwise be masked in a tissue sample with many cell types. Using these techniques, the researchers hope to develop detailed gene expression profiles of the various brain structures and cell types that have been strongly linked to autism.