Researchers have made a huge step forward in understanding autism

In Fragile X Syndrome (FXS), the most common cause of autism, sensory signals from the outside world are integrated differently. (Credit: Getty Images)

In Fragile X Syndrome (FXS), the most common cause of autism, sensory signals from the outside world are integrated differently, resulting in them being underrepresented by cortical pyramidal neurons in the brain.

That is the conclusion of a new study led by a team led by University of Montreal neuroscience professor Roberto Araya, a biophysicist and researcher at UdeM-affiliated CHU Sainte-Justine Research Center.

The phenomenon the team observed could provide important insights into the underlying cause of FXS symptoms and not only provide insight into the mechanism at the cellular level, but also open doors to new targets for therapeutic strategies.

The study was published in the prestigious journal Proceedings of the National Academy of Sciences.

Autism is characterized by a wide range of symptoms that may be related to differences in brain development. Using advanced visualization tools and genetic manipulation of neurons, a team of researchers from the CHU Sainte-Justine Research Center was able to observe the functioning of individual neurons, in particular the pyramidal neurons of cortical layer 5, one of the main neurons for information output to the brain. cortex (a thin layer of tissue on the surface of the brain).

Similar stories

The researchers found a difference in how sensory signals are processed in these neurons.

“Previous work has suggested that FXS and autism spectrum disorders are characterized by cortical hyperexcitability, which is thought to be a major cause of the sensory hypersensitivity seen in autistic people,” said Araya, also a professor in the Department of Neurology at New York University. University of Montreal.

“To our surprise, our experimental results challenge this generalized view that there is a global hypersensitivity associated with FXS in the neocortex. They show that the integration of sensory inputs in cortical neurons is underrepresented in the FXS mouse model,” added Diane E. Michell, first co-author of the study.

The tree image helps illustrate pyramidal neuron morphology and function in Fragile X syndrome. (PREDICTION: Roberto Araya and Soledad Miranda-Rottmann)

The tree image helps illustrate the morphology and function of the 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. Small, leaf-like processes are dendritic spines that contain excitatory synapses that connect one neuron to another. Blurred areas of the image illustrate the altered integration and perception of sensory information from the outside world, discovered by Diana E. Mitchell, Soledad Miranda-Rothmann and colleagues.

missing protein

A protein called FMRP, which is absent from the brains of people with FXS, modulates potassium channel activity in the brain. According to the research team’s work, it is the absence of this protein that changes the way sensory inputs are combined, causing them to be underrepresented by signals from cortical pyramidal neurons in the brain.

Roberto Araya, Soledad Miranda-Rottmann, and Diana E. Mitchell. (CREDIT: Charlene Provost)

Soledad Miranda-Rottmann, also the first co-author of the study, tried to remedy the situation with the help of genetics and molecular biology.

“Even in the absence of the FMRP protein, which performs several functions in the brain, we were able to demonstrate how it is possible to restore the representation of sensory signals in cortical neurons by reducing the expression of a single molecule,” she said.

Altered integration of excitatory inputs into the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X syndrome. (Credit: PNAS)

“This discovery opens the door to new strategies to offer support to people with FXS and possibly other autism spectrum disorders to correctly perceive sensory inputs from the outside world at the level of pyramidal neurons in the cortex,” Araya concluded.

“Even if the over-representation of internal brain signals that cause hyperactivity is not eliminated, correct representation of sensory signals may be sufficient for better processing of signals from the outside world and learning that is better suited to decision making and participation in action. .”

For more good news, check out our Good News section at The bright side of the news.

Note: Materials provided above by the University of Montreal. Content can be edited for style and length.

Do you like such pleasant stories? Get Brighter Side of News Newsletter.