Cell Types, Circuits, and Plasticity in the Mouse Taste System

描述（由申请人提供）：在广泛研究的感觉系统中，例如，视觉，“细胞类型”，从初级神经节细胞开始，已经根据它们的结构和功能进行了分类，并显示出通过大脑内的平行通路进行差异投射。这样的差分投射包括编码和传输感觉刺激的不同方面的平行连线的神经元组，即，在这个系统中，视觉图像。确定从神经节细胞开始的味觉系统是否具有类似的组织是本研究的目标。长期以来的证据，味觉神经节细胞的生理类型，我们最近的证据“形态/连接类型”的味觉神经节细胞的理论和实践基础提出的目标是福音。使用新设计的跨突触顺行病毒，我们将映射一组单味神经节细胞的连接，以充分表征初级感觉神经元的类型，基于它们在两个中央突触上突触接合的中央味觉回路。这些回路将通过神经解剖学研究进行验证，并扩展到一个额外的突触，目标是通过病毒转运确定的位点。此外，该系统如何应对受体细胞的翻转是对味觉的独特挑战，并对感觉编码具有深远的影响。我们的假设是，我们的病毒和神经解剖学研究所揭示的神经节细胞的中央连接是固定的，但它们的外周纤维是可塑的，可以想象随着时间的推移保持稳定的信息，例如，即使在它们翻转时，神经节细胞与相同类型的芽细胞的连接也是如此。我们将通过量化它们的分化率、迁移运动和寿命来表征小鼠味蕾细胞的动态。这将通过用BrdU和受体细胞标记物gustducin或凋亡标记物进行双标记来实现。最后，基于我们展示的离散神经节细胞芽神经支配模式，我们获得了初步证据，一个显着的神经节细胞的可塑性随着时间的推移，附近的芽之间的纤维撤回和部署。我们将研究单个神经节细胞与味蕾的这种关系，随着时间的推移进行染料标记，GAP 43标记生长纤维，以及Brainbow小鼠在单个神经节细胞及其过程中表达不同颜色的荧光。 公共卫生相关性：该项目涉及人类健康的两个方面。它将增加我们对中枢神经系统如何处理味觉信息的理解，这些信息与理解并最终治疗肥胖，高血压和吞咽/摄入后胃肠道疾病等疾病有关。它还将增加对味觉系统神经可塑性的理解，这是探索神经系统损伤后恢复前景的模型。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.