| Autism spectrum disorder(ASD)is a lifelong neurodevelopmental disorder characterized by impaired social(language)interaction,narrow interests,and repetitive stereotypic behaviors.Importantly,most of individuals with autism have cognitive and developmental abnormalities.Due to the wide range of causes and the complexity of the pathology,the pathogenesis of autism is not fully understood and there is a lack of effective clinical treatments.Therefore,research on the mechanisms based on animal models is extremely important for understanding the pathogenesis of autism.Current research on animal models of autism has focused on the genetic,neurological,and pathological mechanisms associated with the phenotypes of social impairment,stereotyped behavior,and abnormal cognitive function.Hearing disorders,such as abnormal speech perception,are frequently reported in individuals with autism.However,the mechanisms underlying these auditory-associated signature deficits in autism remain largely unknown.The BTBR T~+Itpr3tf/J(BTBR)mouse is an idiopathic inbred mouse that stably exhibits a variety of autistic-like behavioral phenotypes,and is now a well-validated animal model for studying the pathology of autism.In this study,we found that BTBR mice displayed significant behavioral impairments while performing the sound frequency discrimination task.Subsequent extra-cellular electrophysiological recordings demonstrated a significant degradation in frequency tuning of neurons in the primary auditory cortex(A1)of these BTBR mice.Further in vitro slice patch-clamp recordings of A1 pyramidal neurons revealed increased neuronal excitability associated with altered excitatory/inhibitory postsynaptic currents.Lastly,substantially altered dendritic spine morphology of pyramidal neurons and decreased parvalbumin inhibitory interneurons in the A1 were also recorded for the BTBR mice.Our results suggest that elevated neuronal excitability,probably due to altered dendritic spine morphology and parvalbumin inhibitory interneurons,contributes to reduced spectral selectivity of A1 neurons and impaired auditory frequency discrimination abilities observed in the BTBR mice.Given the important role of the auditory cortex in processing and perception of acoustic information(including humane speech),our findings in the animal model of autism provide insight into a possible neurological mechanism related to auditory and language-related deficits in individuals with autism. |
