Sensory integration and cognitive inflexibility in rat models of neurodevelopmental disorders

Autism spectrum disorder (ASD) and intellectual disabilities (ID) are complex conditions that affect how individuals perceive and interact with the world. A key challenge in understanding these conditions is identifying how changes in brain function translate into altered behavior. One promising approach is to study the head direction (HD) cell system, a network of neurons that helps animals navigate by encoding their orientation relative to landmarks in the environment.

Previous work on a model of Fragile X syndrome (a leading genetic cause of ASD), revealed that these animals have difficulties integrating sensory cues. Unlike typical rats, which combine visual and self-motion information to navigate, Fmr1-/y rats rely almost exclusively on visual landmarks, indicating a fundamental change in how they process spatial information. Additionally, developmental differences in HD cell function were observed: young Fmr1-/y rats show enhanced spatial tuning, but this advantage disappears in adulthood.

The proposed experiments (in collaboration with the University of Edinburgh, McGill University and Harvard University) will explore two prominent and common features of neurodevelopmental disorders: cognitive inflexibility and sensory hypersensitivity (Rais et al., 2018; Rogers et al., 2003).

We will do so in four models of autism/intellectual disability: the Fmr1-/y , Scn2a+/-, Champ1+/-, and Nlgn3-/y rats. These models were chosen based on the prominence of their association with autism and the expression of the associated proteins in brain areas that represent the outside world.

By combining cutting-edge neuroscience techniques, including electrophysiology, optical imaging, and behavioral tracking, this research aims to identify common neural signatures of ASD/ID. The results could pave the way for new biomarkers and therapeutic strategies while promoting data sharing and collaboration across the autism research community.