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Mouse models of autism respond to therapy targeting the ‘social brain’

by Lindsay Jolivet Aug 25 / 14

Image above: The insular cortex of an autism mouse model is already so strongly activated by a single sensory modality (here a sound) that it is unable to perform its role in integrating information from multiple sources. Image courtesy of MPI of Neurobiology / Gogolla

Mice with behaviour similar to autism have brain abnormalities in an area of the brain tied to empathy, the control of impulses and other social aspects of behaviour.

But some of the abnormality can be repaired with drug therapy during a critical period of brain development, according to a new study  in Neuron co-authored by CIFAR Senior Fellow Takao K. Hensch and CIFAR Global Scholar Alumna Anne Takesian (both Harvard University).

The researchers developed a procedure to measure neuronal activity in an area of the brain known as the insular cortex, and used it to study four existing mouse models of autism. They found that a group of cells scientists already believe to be tied to autism in humans was damaged. The damage impaired the ability of the mice’s brains to process sounds and touch together. These mice are hyper-sensitive to sounds but their brains respond poorly when they are presented with sound and touch stimuli together.

However, treating the mice when they were very young with a type of psychoactive drug, a benzodiazepine, prevented this sensory impairment. Treating adult mice did not work, which suggests there could be a critical period of development for the integration of sound and touch processing. The critical period occurs in young mice, but mice that are older than researchers expected.

The study illuminates brain functions associated with autism that were previously very poorly understood, says Hensch, a fellow of CIFAR’s program in Child & Brain Development and the director of Harvard University’s Conte Center.

In addition, mice that received drug therapy groomed themselves repetitively less often than those that were not treated. The study suggests that the mice could be grooming themselves more often to reduce their hyper-sensitivity to sound or visuals. Hensch says this element could give scientists insight into why humans with autism, who may have similar sensory processing abnormalities, often exhibit repetitive behaviours.

Hensch says this work ties directly to the questions explored in CIFAR’s program in Child & Brain Development.

“Child & Brain Development is devoted to understanding ‘how our earliest experiences play a pivotal role in mental and physical health and adaptive development throughout life.’ Our work lies at the heart of this,” Hensch says.

“The insular cortex remains one of the most mysterious parts of the human brain, responsible for empathy, controlling urges, pain and other aspects of the social brain. It is no wonder that it is routinely impaired in autistic subjects.”

CIFAR’s program in Child & Brain Development explores the core question of how social experiences and settings affect developmental biology and help set early trajectories of lifelong development and health.

“This work is a stunning example of how basic animal research on brain development and function has led to a deeper understanding of autism,” says Program Co-Director Marla Sokolowski (University of Toronto).

The researchers received support from the National Institutes of Mental Health, National Institute of General Medical Sciences, the Human Frontier Science Program, the Charles A. King Trust, and the Nancy Lurie Marks Family Foundation.