Auditory evoked-potential abnormalities in a mouse model of 22q11.2 Deletion Syndrome and their interactions with hearing impairment

Abstract

AbstractBackgroundThe 22q11.2 chromosomal microdeletion is one of the strongest known genetic risk factors for schizophrenia; ∼30% of carriers develop schizophrenia in adulthood. Up to 60% of 22q11.2 deletion carriers also have mild to moderate hearing impairment, primarily from chronic middle-ear inflammation. TheDf1/+ mouse model of the 22q11.2 deletion replicates the large inter-individual variation in hearing ability observed among deletion carriers. Here we used theDf1/+mouse model of the 22q11.2 deletion to investigate how genetic risk for schizophrenia and experience of hearing impairment interact to affect auditory brain function.MethodsWe measured peripheral hearing sensitivity and cortical auditory evoked potentials (AEPs) inDf1/+mice and their WT littermates, exploiting large inter-individual variation in hearing ability amongDf1/+mice to distinguish cortical effects of genetic background from those of experience with hearing impairment. We quantified gain and adaptation of central auditory responses to repeated tone presentations by comparing brainstem and cortical tone-evoked potentials and by analysing the growth of cortical AEPs as tone intensity level or inter-tone interval duration increased.ResultsCentral auditory gain (ratio of tone-evoked cortical and brainstem activity) was elevated inDf1/+mice with hearing impairment. Growth of cortical AEPs with increasing sound level was abnormally large inDf1/+mice regardless of hearing impairment. Finally, growth of cortical AEPs with increasing inter-tone interval was abnormal only forDf1/+mice without hearing impairment.ConclusionsAuditory brain abnormalities in 22q11.2DS are a function of both genotype and hearing phenotype.