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Biologic and Materials Sciences and Division of Prosthodontics

Mistretta Lab Current Research

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To develop neural circuits that are essential for taste sensation, neurons in taste and associated somatosensory sensory ganglia must extend neurites to the tongue and make connections with the taste papilla organs and their resident taste buds. In this proposal, the laboratory continues studies of taste development to focus on two ganglia that innerrvate taste papillae, the geniculate and trigeminal ganglia, and the target organs of these ganglia, the fungiform papillae per se. Goals are to test hypotheses about how the family of neurotrophin molecules modifies ganglion neurophysiology; to discern molecules that regulate papilla development; and, to determine effects of regulatory molecules and target tissues on functional differentiation of innervating ganglia. In vitro approaches are used, including a compartment culture system for embryonic ganglion explants to permit separate molecular maintenance of the neuron cell body, or soma, versus the neurites that grow from the soma, and subsequent electrophysiological recording; and, organ cultures of the entire embryonic rat tongue. These in vitro systems make possible study of molecular affects on cell function in the developing taste system. Aim 1 tests hypotheses that neurotrophins have distinctive spatial and temporal patterns in ganglia and papilla target organs, and that separate and specific neurotrophin exposure at ganglion soma versus growing neurites affects the electrophysiological properties of the ganglion neurons. Aim 2 tests hypotheses about how special signaling molecules called morphogens can regulate formation of fungiform papillae and the patterned distribution of papillae on the tongue. Aim 3 unifies the other two specific aims by testing hypotheses that lingual molecules regulating papilla development can also affect neurophysiological properties of the ganglion neurons that innervate papillae. In Aim 3, an additional hypothesis is to test effects of target and non-target tissues on electrophysiology of ganglion neurons, in compartment cultures. The compartment culture approach to study of ganglion neurophysiology is new to the taste field, and affords opportunities to maintain the neuron cell body with optimal survival molecules, while challenging the growing neurites with molecules and tissues that are present in the embryonic tongue. The whole tongue culture used in Aim 2 provides capability for direct experimental manipulation and evaluation of patterned papilla arrays, not available with other models. There are very few laboratories focused on study of developing neurons and sensory organs in the taste system. Yet such studies are essential for a full understanding of the sense of taste, which motivates our food choices and thereby mediates healthy or unhealthy diet patterns. 
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