Altered stimulus-specific adaptation at the auditory cortex of a mouse model of Fragile X Syndrome

Auditory hypersensitivity or decreased sound tolerance is a common phenotype of Fragile X Syndrome (FXS). Impairments in adaptation, defined as the reduction in the neuronal responsiveness to repeating sounds, can contribute to this prevalent phenotype. Previous studies on event-related potential observed impairments in mismatch negativity (MMN) in both FXS individuals and in the FMR1-knockout (KO) mouse model of FXS. Therefore, in the present study we characterized stimulus-specific adaptation (SSA), a neural correlate of MMN, at the auditory cortex (AC) of anesthetized (with ketamine/xylazine) female and male postnatal day 20 (P20) wild-type (WT) and FMR1-KO mice, using the oddball paradigm with either 4 Hz or 1 Hz repetition rate. We observed robust SSA at the 4 Hz repetition rate of the oddball paradigm in the AC neurons of all four groups of animals. We also noted that the strength of SSA diminished between 4 to 1 Hz repetition rate. In addition, at both the 4 Hz and 1 Hz repetition rate, reduced SSA was observed particularly in the male FMR1-KO mice compared to their WT counterparts, while female WT and FMR1-KO mice displayed similar SSA. In terms of sex differences, male FMR1-KO mice had lower SSA than female FMR1-KO mice, while SSA was similar in male and female WT mice. Overall, our observation of reduced SSA in the male FMR1-KO mice suggests that impairments in neuronal adaptation potentially contribute to the auditory hypersensitivity phenotype particularly within the male population.