Behavioral consequences of induced microgyria: Advancing the application of the rat model for rapid auditory processing impairments

Date of Completion

January 2004

Keywords

Biology, Neuroscience|Psychology, Psychobiology|Psychology, Behavioral

Degree

Ph.D.

Abstract

Focal freezing treatment on postnatal day 1 (P1) in rat pups triggers the formation of microgyric lesions histologically similar to anomalies found in the brains of human dyslexics. Moreover, while humans with various developmental language disabilities have shown rapid auditory processing deficits (and longitudinal studies suggest a predictive relationship), microgyric rats also exhibit auditory processing deficits. Finally, cell size shifts in the medial geniculate nucleus (MGN) of the thalamus have been reported in both human dyslexic and microgyric rat brains. ^ To expand our evaluation of the rodent microgyric model, the current thesis investigated the impact of independent variables such as environment, sex, perinatal experience, severity of injury, age at testing, and repeated behavioral testing on overall brain weight, rapid auditory processing, and MGN cell size. Across all variables, microgyric was associated with reductions in brain weight, (greater in cortical versus non-cortical areas). Moreover in male rats, microgyric was consistently associated with a behavioral impairment regardless of postnatal acoustic environment, experience, age at testing, or amount of cortical damage. Female rats remained resistant to the behavioral effects of induced microgyric, except when exposed to prenatal stress. MGN cell size shifts were only found in microgyric males. However, analysis across studies of the patterns of change in the MGN and auditory processing deficits suggested that the relationship between MGN morphology and behavioral impairment were not directly correlated. ^ Our combined, results suggest that the induced microgyria model may be best described as a “threshold function,” where certain variables influence the likelihood that focal cortical injury during neuralmigration will surpass a “threshold of injury” to result in an observable behavioral deficit and shift in MGN cell size. Further, focal microgyria may impact neurodevelopment in a “trigger” fashion, such that when a certain “minimal level” of injury occurs, some secondary developmental cascade resulting in re-organization of cortical connectivity produces deleterious processing of auditory information. Potential underlying neural mechanisms for this neuronal cascade are discussed, as well as strategies for limiting the likelihood that early damage will trigger a cascade effect. Once triggered, amelioration of the processing impairment may be accomplished with intensive behavioral therapy. ^

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