UC Riverside

Autism spectrum disorder (ASD) is currently diagnosed in approximately 1 in 44 children in the United States, based on a wide array of symptoms, including sensory dysfunction and abnormal language development. Auditory temporal processing is crucial for speech recognition and language development. Abnormal development of temporal processing may account for ASD language impairments. Sex differences in the development of temporal processing may underlie the differences in language outcomes in male and female children with ASD. To understand mechanisms of potential sex differences in temporal processing requires a preclinical model. However, there are no studies that have addressed sex differences in temporal processing across development in any animal model of ASD. My dissertation research utilizes two different mouse models of ASD that display sensory abnormalities: the Fmr1 (Fragile X Messenger Ribonucleoprotein 1) knock-out (KO) mouse model of fragile X syndrome (FXS) and a Pten-deletion (phosphatase and tensin homolog missing on chromosome 10) model of autism. I utilized a 40 Hz gap-in-noise ASSR (auditory steady state response) paradigm and in vivo electrophysiology to measure the cortex's reliability in phase locking to brief gaps in noise at varying modulation depths to assess temporal processing acuity. The Fmr1 study results show gap-ASSR deficits in the frontal (FC), but not auditory (AC), cortex in early development (p21, “postnatal day 21”) in male and female KO mice. Unlike male KO mice, female KO mice show wild type-like temporal processing at p30. This research also utilizes a conditional PTEN KO model that displays a specific gene KO pattern, occurring exclusively in the hippocampus and layers III-V of the cortex. Results show that abnormal PTEN expression significantly impacts oscillatory activity in male and female mice, including abnormal resting power distributions and decreased phase-locking compared to controls. Overall, deficits become more prominent in adult mice. Notably, in both ASD models, female KO mice showed increased auditory hypersensitivity compared to males, reflected as increased ERP amplitudes. This dissertation research has identified similarities and differences between two different autism models. Further unraveling these circuits may be the key to understanding and treating ASD pathology.