In extensively studied sensory systems, e.g., vision, "cell types", beginning with the primary ganglion cells, have been classified on the basis of their structure and function and shown to project differentially via parallel pathways within the brain. Such differential projections comprise parallel-wired sets of neurons that code and transmit different aspects of the sensory stimulus, i.e., in this system, of the visual image. Determining whether the taste system, beginning with the ganglion cells, has a similar organization is the goal of the present research. Long-standing evidence for physiological types of taste ganglion cells, and our recent evidence for "morphological/connectional types" of taste ganglion cells are boons to the theoretical and practical basis for the proposed aims. Using newly engineered trans-synaptic anterograde viruses we will map the connections of a large set of single taste ganglion cells to fully characterize types of primary sensory neurons based on the central taste circuits they synaptically engage across two central synapses. These circuits will be verified and extended one an additional synapse by neuroanatomical study targeting the sites identified with viral transport. Additionally, how the system copes with turn over of receptor cells is a unique challenge for taste and has profound implications for sensory coding. Our hypothesis is that central connections of ganglion cells revealed by our virus and neuroanatomical studies are fixed, but that their peripheral fibers are plastic, conceivably to maintain a stable message over time, e.g. connection of a ganglion cell to the same types of bud cells even as they turn over. We will characterize the dynamism of mouse taste bud cells by quantifying their rate of differentiation, migratory movement, and lifespan. This will be accomplished by double-labeling with BrdU and the receptor cell marker gustducin or an apoptosis marker. Finally, based on our demonstration of a discrete ganglion cell-bud innervation pattern, we obtained preliminary evidence for a remarkable ganglion cell plasticity with withdrawal and deployment of fibers among nearby buds over time. We will study this relationship of single ganglion cells to taste buds with dye labeling over time, with GAP43 labeling for growing fibers, and with Brainbow mice expressing different colored fluorescence in individual ganglion cells and their processes.
This project is relevant to two aspects of human health. It will increase our understanding of how taste information is processed by the central nervous system, information that is relevant to understanding and, ultimately, treating diseases such as obesity, hypertension, and swallowing/post-ingestion gastrointestinal disorders. It will also increase understanding of the neuroplasticity of the taste system, a model for exploring the prospects for recovery of the nervous system after injury.
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