Topography and ensemble activity in auditory cortex of a mouse model of Fragile-X-Syndrome.

Autism spectrum disorder (ASD) is often associated with social communication impairments and specific sound processing deficits, for example problems in following speech in noisy environments. To investigate underlying neuronal processing defects located in the auditory neocortex (AC), we performed two-photon Ca2+ imaging in FMR1 (Fragile X Messenger Ribonucleoprotein 1) knockout (KO) mice, a model for Fragile-X-Syndrome (FXS), the most common cause of hereditary ASD in humans. For primary AC (A1) and the anterior auditory field (AAF), topographic frequency representation was less ordered compared to control animals. We additionally analyzed ensemble AC activity in response to various sounds and found subfield-specific differences. In A1, ensemble correlations were lower in general, while in secondary AC (A2), correlations were higher in response to complex sounds, yet not to pure tones (PT). Furthermore, sound specificity of ensemble activity was decreased in AAF. Repeating these experiments one week later revealed no major differences regarding representational drift. Nevertheless, we found subfield- and genotype-specific changes in ensemble correlation values between the two times points, hinting at alterations in network stability in FMR1 KO mice. These detailed insights into AC networks activity and topography in FMR1 KO mice add to the understanding of auditory processing defects in FXS.Significance statement Communicative challenges often observed in people with autism spectrum disorder might be due to defects in cortical brain circuits responsible for sound analysis. To investigate these in detail, we used a mouse model of Fragile-X-Syndrome, which often is associated with autism spectrum disorder in humans. We found several alterations compared to control animals, including a less well-ordered topography of frequency analysis in auditory cortex. Furthermore, neuronal population activity patterns in response to various sounds were altered. This was also highly dependent on whether pure tones or complex sounds were presented. These data help to understand the causes of sound processing defects in Fragile-X-Syndrome.