Fragile X Syndrome: New Insights into Autism Neurology

Author: University of Montreal
Published: 2023/02/16 - Updated: 2026/01/14
Publication Details: Peer-Reviewed, Findings
Category Topic: Autism - Related Publications

Page Content: Synopsis - Introduction - Main - Insights, Updates

Synopsis: This research represents a peer-reviewed study from the University of Montreal that challenges previous assumptions about autism and Fragile X syndrome. Published in the Proceedings of the National Academy of Sciences, the findings demonstrate that sensory signals from the external environment are underrepresented rather than over-represented in cortical pyramidal neurons of individuals with Fragile X syndrome, the most common genetic cause of autism. The work provides valuable insight for families, caregivers, and healthcare professionals supporting autistic individuals, as it identifies specific cellular mechanisms that could lead to new therapeutic approaches for improving sensory signal processing. The research is particularly relevant for those seeking evidence-based explanations for sensory processing differences commonly experienced by people with autism spectrum disorders - Disabled World (DW).

Definition: Fragile X Messenger Ribonucleoprotein 1 (FMR1) - Fragile X Messenger Ribonucleoprotein (FMRP): FMR1 (Fragile X Messenger Ribonucleoprotein 1) is a human gene that codes for a protein called fragile X messenger ribonucleoprotein, or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development and female reproductive function. Mutations of this gene can lead to fragile X syndrome, intellectual disability, premature ovarian failure, autism, Parkinson's disease, developmental delays, and other cognitive deficits. In healthy neurons, FMRP modulates the local translation of numerous synaptic proteins. Synthesis of these proteins is required for the maintenance and regulation of long-lasting changes in synaptic strength. FMRP exerts profound effects on synaptic plasticity in this role as a translational inhibitor.

Introduction

Altered Integration of Excitatory Inputs onto the Basal Dendrites of Layer 5 Pyramidal Neurons In a Mouse Model of Fragile X Syndrome - Proceedings of the National Academy of Sciences

Results of a new study led by Roberto Araya, a Canadian neuroscientist, biophysicist, and researcher at the CHU Sainte-Justine Research Centre in Montreal, show that in Fragile X syndrome (FXS), the most common cause of autism, sensory signals from the outside world are integrated differently, causing them to be underrepresented by cortical pyramidal neurons in the brain.

Main Content

This phenomenon could provide important clues to the underlying cause of the symptoms of this syndrome. The research team's work not only provides insight into the mechanism at the cellular level but also opens the door to new targets for therapeutic strategies.

The study was published on January 3, 2023, in the prestigious journal Proceedings of the National Academy of Sciences.

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

An image of the tree illustrates the morphology and function of pyramidal neurons in autism spectrum disorders. These neurons are one of the main integrators of information in the cerebral cortex, with long branches and roots representing dendrites. The small leaf-like projections are the dendritic spines, where the excitatory synapses are located - connecting one neuron to another. The blurred sections of the image represent the altered integration and perception of sensory information from the outside world, discovered by Diana E. Mitchell, Soledad Miranda-Rottmann, and colleagues. Image Credit: Photo and drawing by Roberto Araya and Soledad Miranda-Rottmann. The photo was taken at Westmount Park, Montreal, Canada.

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 a hyperexcitable cortex, which is considered to be the main contributor to the hypersensitivity to sensory stimuli observed in autistic individuals," said Araya, also a professor in the Department of Neurosciences at Université de Montréal.

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

A protein, FMRP, that is absent in the brains of people with FXS modulates the activity of a type of potassium channel in the brain. According to the research group's work, the absence of this protein alters the way sensory inputs are combined, causing them to be underrepresented by the signals coming out of the cortical pyramidal neurons in the brain.

Soledad Miranda-Rottmann, also the first co-author of the study, attempted to rectify the situation with genetic and molecular biology techniques. "Even in the absence of the FMRP protein, which has several functions in the brain, we were able to demonstrate how the representation of sensory signals can be restored in cortical neurons by reducing the expression of a single molecule," she said.

"This finding opens the door to new strategies to offer support to those with FXS and possibly other autism spectrum disorders to correctly perceive sensory signals from the outside world at the level of pyramidal neurons in the cortex," concluded Araya.

"Even if the over-representation of internal brain signals causing hyperactivity is not addressed, the correct representation of sensory signals may be sufficient to allow better processing of signals from the outside world and of learning that is better suited to decision making and engagement in action."

Insights, Analysis, and Developments

Editorial Note: The implications of this neuroscience research extend well beyond the laboratory. By pinpointing how a single protein's absence alters the way neurons process sensory information, scientists have opened a pathway toward treatments that could help autistic individuals better interpret their sensory environment. What makes this work particularly significant is its shift away from the long-held belief in cortical hyperexcitability as the primary mechanism behind sensory sensitivities in autism. Instead, the team discovered an under-representation of sensory signals in key brain regions - a finding that could reshape how we approach both diagnosis and intervention. For families navigating the complexities of Fragile X syndrome and autism, this research offers something increasingly rare in medical science: a clear, measurable target for future therapies that might meaningfully improve daily functioning and quality of life - Disabled World (DW).

Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by University of Montreal and published on 2023/02/16, this content may have been edited for style, clarity, or brevity.