Tweaking Electrical Activity in the Brain Impairs and Restores Mouse Social Behaviors

Researchers pioneer technique to test how changes in brain activity may produce autism symptoms

Researchers altered the social behavior of mice by using light to manipulate electrical activity in a brain region involved in learning and socializing. The study, published this fall in Nature, bolsters the theory that autism may stem from an imbalance in the natural signals that excite or dampen activity within the brain. The study also offers a new approach to creating animal models of autism—crucial for testing promising medicines that might relieve disabling symptoms.

Using a technique he pioneered and dubbed “optogenetics,” Stanford University psychiatrist Karl Deisseroth, M.D., Ph.D., and his colleagues engineered mice to produce light-sensitive proteins in the prefrontal cortex—a region involved in learning and social behavior. In a typical brain, some cells send signals that excite brain activity while other cells send signals that quiet it. In the optogenetic mice, excitatory brain cells respond to blue light and inhibitory brain cells respond to yellow light.

As a result, the researchers could dial up or dial down the level of activity in a mouse’s prefrontal cortex with pulses of light sent through a fiber optic cable implanted in its brain. The light’s effect lasted up to a half hour, enabling the researchers to remove the visible portion of the fiber optic implant and observe how the mice interacted with new mice or objects placed in their enclosures.

When the mice were exposed to blue light alone, they abruptly lost interest in socializing with new mice. By contrast, typical mice readily approach and sniff newcomers. However, the blue-light stimulated mice did not display other deficits such as difficulty adjusting to new objects placed in their cages.

When both excitatory and inhibitory cells were turned on simultaneously (by exposure to blue and yellow light), the mice resumed typical social behaviors.

The findings support a theory that autism stems from a dysregulation of normal brain signaling. Other evidence supporting this idea includes the fact that about one-third of those with autism also suffer seizures, a result of excessive electrical activity in the brain. In addition, several of the altered genes associated with autism play a role in brain signaling. Also, brain imaging studies reveal that some people affected by autism show higher than normal activity in brain regions associated with social behavior.

This latest experimental evidence further suggests that restoring balance to brain activity may be a way to relieve some of autism’s core symptoms. It also provides groundwork for future research investigating the role that specific brain circuits play in autism. Deisseroth and his colleagues are already developing new mouse models that will allow scientists to manipulate the activity of other brain regions and circuits, promising a more precise picture of how brain signaling problems might give rise to autism’s core symptoms.

Yizhar O, Fenno LE, Prigge M, et al. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature. 2011 Jul 27;477(7363):171-8.

 

Next: More Evidence Linking Immune System to Some Forms of Autism...

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