Mouse studies show 'inhibition' theory of autism wrong

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The major hypothesis today—one supported by many animal studies—has been that in the receive too little or too much excitation, which causes hyperexcitability or increased "spiking." This excess spiking is thought to act as noise that interferes with normal function. Such noise could lead to the characteristic symptoms of autism in humans: problems with social interactions, language deficits, repetitive thoughts and behaviors and hypersensitivity to sensory stimuli.


In a new study, however, University of California, Berkeley, neuroscientists demonstrated that while inhibition does decrease in the brains of these mice, altering the balance between excitation and inhibition, the changed balance does not affect spiking at all. Instead, this altered balance seems to be a compensatory mechanism that stabilizes brain activity in response to the disorder.

"Many groups are searching for ways to increase inhibition in the brain, either through drugs or through gene therapy, on the assumption that increasing inhibition will restore the brain back to normal," said study leader Daniel Feldman, a UC Berkeley professor of molecular and cell biology and member of the Helen Wills Neuroscience Institute. "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."



Autistic mice

"Autism is a big puzzle," Feldman said. "The main advance in the past 10 years has been to show that a very high fraction—at least 50 percent—of the risk for autism is actually genetic. But it is not a , it is hundreds of genes. How do you understand how multiple gene mutations can all lead to similar—not the same, but similar—kinds of disorders along the spectrum that we call autism?"





He views this as a highly effective accommodation by neurons to these genetic mutations, representing the brain's normal compensation mechanism for restoring neuronal activity. But decreased inhibition may have unwanted secondary effects that impair other aspects of neural information processing, such as the tuning each neuron has to specific stimuli.

"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 suggests. "So even though there are not more spikes, the spiking could encode information less precisely."

He is continuing his studies to determine what other effects lowered inhibition have that could explain symptoms. He is focusing on mice that also have sensory impairment, such as hypersensitivity to sound or touch, in addition to antisocial and repetitive behaviors.

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Autism may reflect excitation-inhibition imbalance in brain, study finds

Journal information: Neuron

Citation: Mouse studies show 'inhibition' theory of autism wrong (2019, January 21) retrieved 13 October 2019 from https://medicalxpress.com/news/2019-01-mouse-inhibition-theory-autism-wrong.html

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