Autism spectrum disorders (ASDs) are characterized by several broad diagnostic features, with one of the most prominent being an inability for social or emotional reciprocity. The long-term objective of this grant proposal is to identify specific sites in the brain that can be used as targets for the development of more effective and more specific pharmaco-therapeutic interventions for social ailments that characterize conditions like ASD. The proposed experiments will utilize a model of autism (i.e., the BALB/cJ-C57BL/6J model of sociability) to elucidate regions of the mammalian brain that are involved in the detection and response to stress in others. The research strategy for this grant proposal is based on the premise that development of a robust model of sociability will generate fundamental knowledge regarding the mammalian ?social brain? in both healthy and diseased states.
The specific aims of this proposal can be summarized within the context of the training program for the PI:
Specific Aim 1 - Delineate regions of the brain that express vicarious metabolic and transcriptional responses to stress, which will provide the PI with a training opportunity to acquire expertise in metabolic brain mapping and inducible transcription factor immunohistochemistry.
Specific Aim 2 - Employ a localized brain inactivation procedure to modulate a behavioral response that is sensitive to the induction of stress in others, which will allow the PI to acquire expertise in procedures that are used for site-specific, reversible brain inactivation techniques.
Specific Aim 3 - Characterize the physiological activity of individual neurons in response to presentation of cues that indicate stress in others, which will give the PI an excellent training experience in state-of-the-art electrophysiological recording techniques.
A core feature of the autism spectrum diagnosis is an inability for social or emotional reciprocity. Mice have become a preeminent model system for translational autism research, and individuals from this species are able to detect and respond to stress in others. This project seeks to identify the neuroanatomical and neurophysiological substrates that underlie genetic influences on the ability to detect stress in others.
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