Roberto Araya
Credit: Courtesy Photo
The results of a new study led by neuroscientist Roberto Araya, researcher at the CHU Sainte-Justine Research Center and professor in the Department of Neurosciences at the University of Montreal, show that in fragile X syndrome, the cause the most common feature of autism, sensory signals from the outside world are integrated differently, causing them to be underrepresented by cortical pyramidal neurons in the brain. This phenomenon could provide important clues to the origin of the manifestations of this syndrome. The work of the research team not only makes it possible to understand the mechanism at the cellular level, but it also opens the door to new targets for therapeutic strategies.
L’study was published on January 3 in the American journal Proceedings of the National Academy of Sciences.
Autism is characterized by a wide range of symptoms that could stem from different brain development. Thanks to technological advances in brain imaging and genetics, the CHU Sainte-Justine team was able to observe the functioning of individual neurons and focus on the pyramidal neurons of cortical layer 5 – which are among the main Brain output neurons in the cortex (that thin layer of brain tissue that covers the brain).
She then noticed a difference in the way sensory signals are processed in these neurons. “Previous work suggested that fragile X syndrome was characterized by a hyperexcitable cortex, considered the main contributor to the sensory hypersensitivity observed in people with autism,” explains Roberto Araya.
Credit: Roberto Araya and Soledad Miranda-Rottmann
“To our surprise, our results challenge this generalized view. They show that the integration of sensory signals in the neurons of the cortex is underrepresented in a mouse model with Fragile X”, continues Diana E. Mitchell, first co-author of the study and recipient of a research grant. postdoctoral fellowship of the Autism Research Training Program – Quebec.
The tree image illustrates the morphology and function of pyramidal neurons in fragile X syndrome. These neurons are one of the main information integrators in the cerebral cortex, with long “branches” and “roots” representing dendrites. The little “leaf-like” protrusions are the dendritic spines, where the excitatory synapses are located — connecting one neuron to another. The blurred sections of the image illustrate the impaired integration and perception of sensory information from the outside world discovered by Diana E. Mitchell, Soledad Miranda-Rottmann and their colleagues.
How to explain this difference?
A protein, FMRP, absent from the brains of people with fragile X syndrome, modulates the activity of a type of potassium channel in the brain. According to the research group’s work, it is the absence of this protein that alters the way sensory inputs are combined and causes their under-representation by outgoing signals from cortical pyramidal neurons in the brain.
Soledad Miranda-Rottmann, also the first co-author of the study, managed to restore the situation with genetic and molecular biology techniques. “Even in the absence of the FMRP protein, which has multiple functions in the brain, we demonstrated how the representation of sensory signals can be restored by reducing the expression of a single molecule,” she says.
“This discovery opens the door to new therapies to help people with fragile X syndrome correctly perceive signals from the outside world. Even if the overrepresentation of internal brain signals causing hyperactivity remains unaddressed, the correct representation of sensory signals may prove sufficient to allow better integration of signals from the outside world and better learning. adapted to decision-making and commitment to action,” says Roberto Araya.