The research and career development plans proposed in this application will expand the candidate's expertise in neuropharmacology, normal and abnormal socioemotional development, epileptology, and magnetic resonance imaging (MRI) as applied to neurodevelopmental disorders such as autism, mental retardation, and cerebral palsy. The Research Plan proposed will take advantage of the recent evidence that dysfunction in medial temporal lobes, and the amygdala in particular, may be an etiological factor in autism. The goal of the application is to investigate the role of amygdala and its specific subdivisions for socioemotional behavior, and to identify the critical periods and neural triggers for developmental abnormalities in an animal model of autism.
Specific Aim 1 concentrates on the effects of pharmacologically induced imbalances in neurotransmission in amygdala on social interactions in infant animals.
Specific Aim 2 will compare the effects of drugs (as obtained in Aim 1) with the effects of discrete lesions of subregions of amygdala, damaged by axon-sparing lesions.
Specific Aim 3 will evaluate the effects of early prolonged seizures, known to disrupt the function of amygdala and its projection network, on the neurodevelopmental behavioral outcomes. The experiments designed to pursue these aims will provide an opportunity for the candidate to gain both theoretical and practical expertise in the combined use of pharmacological, physiological, and MRI approaches to the study of the animal models. The candidate's background in behavioral research will be applied to the analyses of various components of socioemotional interactions of infant and juvenile animals in dyads and the assessment of their cognitive functions. The career development plan will facilitate a substantial shift in the candidate's research capabilities and scope, so that it will become possible for her to build an independent research program devoted to the identification of neural mechanisms underlying autism and other developmental disorders. The ability to evaluate the multifactorial impact of pharmacological interventions in animal models will prepare the candidate to pursue research on animal models of neurodevelopmental disorders and place her research skills in the context of pharmacology, epileptology, and physiology. Structured activities and short courses will guide the development of expertise in these areas necessary for the proposed studies as well as for the long-term career advancement of the candidate as a versatile neuroscientist. ? ?
