A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Winter, 2019 | Number 1, Volume 33

Inhibition-excitation alterations in ASD: a surprising finding

The findings of a new study cast doubt on the hypothesis that autism symptoms such as sensory oversensitivity stem from too little inhibition or too much excitation of neurons, causing hyperexcitability or increased “spiking” that interferes with brain function. 

Michelle Antoine and colleagues tested four mouse models of autism, each involving a single genetic defect similar to one found in humans with autism spectrum disorders (ASD). They did find that inhibition was lower than normal in the neurons of the mice and that excitation was reduced to a lesser degree, resulting in an increase in the excitation-inhibition ratio. However, they discovered that the neurons maintained a normal spiking rate because the changes in inhibition and excitation were precisely coordinated to offset each other. The researchers say that this may be how the neurons compensate for the genetic mutations so they can stabilize brain activity.

Lead author Daniel Feldman says, “Many groups are searching for ways to increase inhibition in the brain, either through drugs or gene therapy, on the assumption that increasing inhibition will restore the brain to normal. But actually, our results suggest that loss of inhibition might represent a useful compensation that the brain is doing, or might be unrelated to disease symptoms. And if you go in there and increase inhibition, you might make things worse or you might not affect things at all.”

Feldman says that while decreased inhibition appears to help neurons maintain stable brain activity, it may cause unwanted secondary effects. “Changes in the excitation-inhibition ratio might be successfully compensating to maintain a relatively normal firing rate, but a side effect of that compensation may be that they degrade the precision of the coding information,” he says. “So even though there are not more spikes, the spiking could encode information less precisely.”


Citations

“Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models,” Michelle W. Antoine, Tomer Langberg, Philipp Schnepel, and Daniel E. Feldman, Neuron, January 21, 2019 (online). Address:

Michelle Antoine, [email protected].

—and—

“Mouse studies question ‘inhibition’ theory of autism,” Robert Sanders, Berkeley News, January 21, 2019.