Many people with autism spectrum disorders are highly sensitive to light, noise, and other sensory input.
In a new study, researchers found a neural circuit that appears to underlie this hypersensitivity, offering a possible strategy for developing new treatments.
The research was conducted by MIT and Brown University neuroscientists.
In the study, the team found that mice lacking a protein called Shank3, which has been previously linked with autism, were more sensitive to a touch on their whiskers than genetically normal mice.
These Shank3-deficient mice also had overactive excitatory neurons in a region of the brain called the somatosensory cortex, which the researchers believe accounts for their over-reactivity.
There are currently no treatments for sensory hypersensitivity, but the researchers believe that uncovering the cellular basis of this sensitivity may help scientists to develop potential treatments.
They hope the research can point to the right direction for the next generation of treatment development.
The Shank3 protein is important for the function of synapses—connections that allow neurons to communicate with each other.
The team has previously shown that mice lacking the Shank3 gene display many traits associated with autism, including avoidance of social interaction, and compulsive, repetitive behavior.
In the study, they wanted to know whether these mice also show sensory hypersensitivity.
For mice, one of the most important sources of sensory input is the whiskers, which help them to navigate and to maintain their balance, among other functions.
The researchers developed a way to measure the mice’s sensitivity to slight deflections of their whiskers, and then trained the mutant Shank3 mice and normal (“wild-type”) mice to display behaviors that signaled when they felt a touch to their whiskers.
They found that mice that were missing Shank3 accurately reported very slight deflections that were not noticed by the normal mice.
Once they had established that the mutant mice experienced sensory hypersensitivity, the researchers set out to analyze the underlying neural activity.
To do that, they used an imaging technique that can measure calcium levels, which indicate neural activity, in specific cell types.
They found that when the mice’s whiskers were touched, excitatory neurons in the somatosensory cortex were overactive. This was somewhat surprising because when Shank3 is missing, synaptic activity should drop.
That led the researchers to hypothesize that the root of the problem was low levels of Shank3 in the inhibitory neurons that normally turn down the activity of excitatory neurons.
Under that hypothesis, diminishing those inhibitory neurons’ activity would allow excitatory neurons to go unchecked, leading to sensory hypersensitivity.
To test this idea, the researchers genetically engineered mice so that they could turn off Shank3 expression exclusively in inhibitory neurons of the somatosensory cortex.
As they had suspected, they found that in these mice, excitatory neurons were overactive, even though those neurons had normal levels of Shank3.
The results suggest that reestablishing normal levels of neuron activity could reverse this kind of hypersensitivity.
Many other studies in mice have linked defects in inhibitory neurons to neurological disorders, including Fragile X syndrome and Rett syndrome, as well as autism.
The team now plans to study the timing of when these impairments arise during an animal’s development, which could help to guide the development of possible treatments.
There are existing drugs that can turn down excitatory neurons, but these drugs have a sedative effect if used throughout the brain, so more targeted treatments could be a better option.
The lead author of the study is Guoping Feng, the James W. and Patricia Poitras Professor of Neuroscience at MIT.
The study is published in Nature Neuroscience.
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