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A detailed study of four models of autism in the mouse challenges the most common badumption about what is wrong with the brain circuits to cause the symptoms of the disease.
The major hypothesis today – a hypothesis supported by numerous animal studies – has been that autistic brain neurons are subject to insufficient inhibition or excessive excitation, causing hyperexcitability or an increase in "pecking". ". This excess of peaks is thought to act as a noise that interferes with the normal functioning of the brain. 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.
The researchers are even looking for ways to increase the overall inhibition of neurons in the brain in order to restore the balance between excitation and inhibition and hopefully , reduce the symptoms.
In a new study, however, neuroscientists at the University of California at Berkeley have demonstrated that, although inhibition is decreasing in the brains of these mice and altering the balance between excitation and inhibition, the modified equilibrium does not affect in no way doping. Instead, this altered balance appears to be a compensatory mechanism that stabilizes brain activity in response to the disease.
"Many groups are looking for ways to increase inhibition in the brain, through drugs or through gene therapy, baduming that increasing inhibition will restore the brain to normal" said Daniel Feldman, director of the study, professor of molecular biology and synthesis at the University of Berkeley. cell biology and a member of the Helen Wills Neuroscience Institute. "But in reality, our results suggest that the loss of inhibition might represent a useful compensation by the brain, or may not be related to the symptoms of the disease." And if you increase inhibition, you risk Make things worse or not affect things at all. "
The discovery should send the researchers back to the lab to determine the real cause of the decrease in inhibition and increased arousal, as well as the role these changes play, if any, in the brain, a- he declared.
Feldman and colleagues at UC Berkeley will report their findings on January 21 in the newspaper neuron.
Autistic mice
"Autism is a big puzzle," Feldman said. "The main breakthrough of the last 10 years has been to show that a very high fraction – at least 50% – of the risks for autism is actually genetic, but it is not a single gene, it is hundreds of genes How do you understand how multiple gene mutations can all lead to types of disorders similar to what we call autism?
Mouse models have helped a lot, he said. Each mouse strain was modified with a single genetic mutation identical to one of the tens already discovered in autistics. Mice exhibit behaviors similar to those of human autism, primarily altered social interactions and repetitive behaviors.
"With these mouse models, researchers want to test different strategies to improve symptoms, but before we can do it effectively, we need to determine what is wrong with the brain mechanically to generate the cognitive, motor and behavioral symptoms of the brain. Autism, "he said.
He chose four well – validated mouse models, each with a single genetic defect mimicking that found in humans, and studied the properties of synapse and neuron firing in order to systematically test the theory of the mouse. balance excitation-inhibition. In all mice, the inhibition was lower than normal and the excitation was also lower, although less strong, which resulted in an increase in the excitation-inhibition ratio. The standard hypothesis predicts that this increase in the ratio should have led to more triggers or peaks of neurons.
He found, however, that although the excitation / inhibition ratio was higher than in the normal mouse brain, the neurons maintained a normal doping level. Indeed, the changes of inhibition and excitation were precisely coordinated to compensate each other.
He sees this as a very effective adaptation of neurons to these genetic mutations, representing the normal clearing mechanism of the brain to restore neuronal activity. But reduced inhibition may have undesirable side effects that interfere with other aspects of neuronal information processing, such as the adaptation of each neuron to specific stimuli.
"Changes in the excitation-inhibition ratio could help to successfully offset the maintenance of a relatively normal trigger rate, but one of the side effects of this compensation could be that" they degrade the accuracy of the coding information, "he suggests. "So, even if there are no more spikes, these could code information less precisely."
He is continuing his studies to determine what other effects might have on the symptoms of autism, which could explain the symptoms of autism. It focuses on mice also showing sensory impairment, such as hypersensitivity to sound or touch, as well as antisocial and repetitive behaviors.
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