Representation of high and low frequency mouse vocalizations in the auditory midbrain and amygdala of Fragile X mice

Fragile X syndrome (FXS), is the most common monogenetic cause of mental impairment and autistic traits. Symptoms in people with FXS include auditory hypersensitivity and communication problem, which is recapitulated in the FXS mouse model. Previous studies in FXS mice showed only moderate increased neural activity levels in different parts of the ascending auditory pathways in response to simple tones. Here we characterized whether complex sounds with a behavioural relevance, such as vocalizations, evoke neural activity patterns that differ between FXS KO and WT mice. We used playback of low- frequency broadband vocalizations (squeaks), ultra-sonic vocalizations (USVs), frequency matched pure tones and silence and compared neural activity levels in the auditory midbrain and the amygdala by immunohistochemically labelling the immediate-early gene c-fos directly after sound exposure. In the auditory midbrain the number of c-fos positive neurons was elevated in FXS mice in response to squeaks, but not in response to a pure tone with a similar frequency. A similar trend was observed in the anterior part of the basolateral amygdala of FXS mice This was also true for USV presentation. A second set of experiments compared multiunit activity levels in response to vocalization playbacks in the auditory midbrain of FXS and WT mice using neuropixel probes. Preliminary analysis comparing genotypes shows a spatial shift of neural activity within the auditory midbrain in the representation of squeaks and USVs. To what extend playback of different vocalizations affects the behaviour of FXS mice is being analysed at the moment.