A quarterly publication of the Autism Research Institute
Summer, 2017 | Number 3, Volume 31
A new study offers strong evidence that autism spectrum disorders (ASD) involve an imbalance in signaling by excitatory and inhibitory neurons in one region of the brain.
In 2011, Karl Deisseroth and colleagues found that activating excitatory neurons in the prefrontal cortex caused mice to lose interest in socializing with other mice, indicating that over-excitation in this brain region can contribute to social impairments. In the new study, Deisseroth and his team—including lead author Aslihan Selimbeyoglu—explored the effects of altering the excitatory-inhibitory balance in the brains of mice with a mutation corresponding to a mutation associated with ASD in humans.
In this study, the researchers used mice lacking both copies of CNTNAP2. These mice are less sociable and more hyperactive than typical mice. In addition, like humans with the equivalent mutation, they have a shortage of a type of inhibitory neurons called parvalbumin neurons.
Deisseroth and his team used a technique called optogenetics to insert genes for two types of light-sensitive proteins, or opsins, into two sets of neurons in the medial prefrontal cortex of the mice. Using an implanted optical fiber that delivered a pulse of blue light, the researchers were able to alter the responses of the neurons. One type of opsin caused inhibitory parvalbumin neurons to become more active, while the other type made excitatory pyramidal neurons less active. In both interventions, the researchers found that the mice became significantly more sociable and less hyperactive.
The researchers, who have previously used optogenetic interventions to reduce anxiety, depression, and obsessive-compulsive symptoms in mice, conclude, “This study highlights the potential for modulating neural circuits in the brain as a strategy for treating autism.”
“Modulation of prefrontal cortex excitation/ inhibition balance rescues social behavior in CNTNAP2-deficient mice,” Aslihan Selimbeyoglu, Christina K. Kim, Masatoshi Inoue, Soo Yeun Lee, Alice S. O. Hong, Isaac Kauvar, Charu Ramakrishnan, Lief E. Fenno, Thomas J. Davidson, Matthew Wright, and Karl Deisseroth, Science Translational Medicine, Vol. 9, Issue 401, August 2, 2017. Address: Karl Deisseroth, [email protected].
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“Autism may reflect excitation-inhibition imbalance in brain,” Bruce Goldman, Stanford University, August 2, 2017.
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“Scientists use light to turn off autism symptoms in mice,” Nicholette Zeliadt, Scientific American, August 3, 2017
