Signal Transduction Mechanisms in Neuroendocrine Neurons

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DESCRIPTION (provided by applicant): Corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVH) are critical for adaptive responses to stress, disruptions of which may be linked to stress-related pathologies. The long-term objective of this training proposal is to begin establishing the precise relationships among stimuli that evoke stress responses, the neural pathways conveying that information to the PVH, and the coordinated response of PVH neurons to such information. Specific aims all center around how the hindbrain-originating catecholaminergic (CA) afferents help trigger gene expression in CRH neuroendocrine neurons of the rodent PVH in response to the metabolic stressor, 2-deoxyglucose (2-DG). Proposed training includes: (1) immunohistochemistry and in situ hybridization to track cellular markers of CRH neuronal activity (e.g., MAP kinase, CREB, crh hnRNA), (2) intravenous 2-DG or PVH injection of a retrograde immunotoxin to selectively stimulate or lesion, respectively, the CA afferent system, and (3) PVH microinjections of receptor antagonists or enzyme inhibitors to probe the signaling machinery of CRH neurons. This training will further my career goal of studying cellular signaling using an in vivo approach.