IS ASTROCYTE ACTIVITY ALTERED IN THE DEVELOPING AUTISTIC-LIKE BRAIN?

Autism spectrum disorder (ASD) is characterised by disruptive sensory processing patterns that include intense hypersensitivities and atypical sensory gating. The neurobiological basis of these abnormalities however remains poorly understood. Emerging evidence links astrocytes, which interact closely with neurons during early development, as potential key players in activity-dependent circuit maturation, particularly within the auditory system. In this project, we investigate astrocyte activity in the developing auditory circuit in vivo in two well-established ASD mouse models: Fragile-X Syndrome knockout (FMR1 KO) and the inducible valproic acid model. Leveraging the postnatal onset of hearing in mice, we compare astrocytic circuit dynamics in these models before hearing onset and correlate them to their ultrasonic vocalisations (USVs), which are known to be altered in ASD mouse models. By using unanesthetised transgenic mice expressing calcium indicators such as GCaMP, we can perform in vivo calcium imaging through cranial windows to analyse astrocyte activity. We hypothesize that greater deviations in astrocyte activity would correlate with more pronounced alterations in USV patterns. By characterising astrocytic function within these models, we aim to shed light on the developmental origins of sensory processing deficits in ASD, specifically focusing on the contribution of astrocytes, and pave the way to identify new therapeutic approaches for managing these debilitating symptoms.