My prior research has used neuroanatomical tracing methods and immunocytochemistry to examine central synaptic inputs to gastric vagal motor neurons in adult rats, and to examine the vagal innervation of the stomach and other digestive viscera in maturity and during fetal and postnatal development. The present application reflects my strong desire to expand this approach to include functional ontogenetic analyses of the central neural connections of the vagus that influence three critical components of homeostatic control: pituitary neuroendocrine secretion, gastric physiology, and ingestive behavior.The proposed experiments are organized into three studies. The first study will analyze the structural (anatomical) development of ascending and descending neural projections between gastric vagal regions of the nucleus of the solitary tract (NST) and the hypothalamus, focusing on ascending projections from catecholaminergic NST neurons to the paraventricular nucleus (PVN) of the hypothalamus and descending projections from PVN oxytocinergic neurons to the NST. The second study will extend these anatomical analyses by examining the functional maturation of ascending gastric vagal sensory inputs that are relayed through catecholaminergic projections from the NST to magnocellular and parvocellular PVN neurons. This study will radioimmunoassay plasma levels of oxytocin in response to gastric vagal stimulation to determine the postnatal development of vagally-mediated pituitary secretion. In addition, tract-tracing and neurotransmitter immunocytochemistry will be used in conjunction with immunocytochemical detection of cFos protein to define the subnuclear distribution, chemical phenotypes, and axonal projections of NST and hypothalamic neurons that receive gastric sensory signals at different postnatal ages. The third study will examine the functional maturation of inhibitory hypothalamic control over ingestive behavior and vagally-mediated gastric motility. This study will use physiological and behavioral methods to analyze the ontogeny of """"""""dehydration anorexia"""""""" and inhibition of gastric emptying following stimulation of osmoreceptors in the basal forebrain that communicate through oxytocinergic projections from the PVN to the NST. The relationship between cFos expression by magnocellular neurons and pituitary secretion of OT in neonates also will be examined, as will the axonal projections and chemical phenotypes of PVN and NST neurons expressing cFos in response to osmotic stimulation. The proposed studies will further characterize the ontogeny of homeostatic responses to gastric and osmotic stimulation, and the central neural circuits that mediate these responses.
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