Contribution of Multisensory Stimuli on Entorhinal Circuit Dynamics and the Menta

描述（由申请人提供）：几种神经和精神疾病，包括阿尔茨海默氏症和精神分裂症，在空间记忆任务中表现出缺陷。毫不奇怪，被认为负责空间记忆形成的大脑区域-海马体和上游内嗅皮层-显示出相关的缺陷。内嗅皮层整合来自所有感觉方式的信息，然后将这些信息传递到海马体，在那里形成认知地图。这两个区域之间的连接与阿尔茨海默氏症和精神分裂症都有关系：导致阿尔茨海默氏症的tau蛋白在突触中传播，而错误的连接可能是精神分裂症症状的一个子集。因此，了解内嗅皮层和海马内部和之间的电路是基础和转化研究的重要奋进。 本项目旨在了解内嗅皮层和海马的驱动感觉模式，并了解两个结构内和之间的电路。为此，当老鼠在虚拟现实中探索环境时，将记录单个神经元的放电活动。虚拟现实是必要的，以精确地控制空间信息的感官线索的性质和可用性。在该设计中，响应于刺激的变化的激发特性的变化可以归因于该感觉模态与感兴趣的大脑区域之间的强连接。进一步的结论，可以考虑海马和内嗅皮层的感觉方式的差异影响。 感兴趣的细胞类型是海马位置细胞，其以空间选择性方式激发;内侧内嗅网格细胞，其具有空间周期性场;内侧内嗅边界细胞，其沿着环境的边界激发;以及外侧内嗅细胞，其响应于环境内的物体而激发。这个项目的目的是区分远端视觉，自我运动和近端线索对这些细胞类型的firng的相对驱动力。此外，将通过抑制边缘细胞的输出和观察对网格细胞的影响来探索中内嗅皮层内两种不同细胞类型之间的关系。 确定不同的环境刺激对内嗅皮层细胞的贡献将提供有关其形成的重要见解，以及大脑作为一个整体如何编码空间记忆并产生空间的心理表征。了解健康大脑中的回路将为解决复杂的精神疾病提供更多的牵引力。

DESCRIPTION (provided by applicant): Several neurological and psychiatric disorders, including Alzheimer's and schizophrenia, show deficits in spatial memory tasks. Not surprisingly, the same brain areas thought to be responsible for spatial memory formation - the hippocampus and upstream entorhinal cortex - show correlated deficits. The entorhinal cortex integrates information from all the sensory modalities and then passes this information to the hippocampus, where the cognitive map is formed. Connectivity between the two regions has been implicated in both Alzheimer's and schizophrenia: the tau protein that causes Alzheimer's spreads across synapses, and errant connectivity might be responsible for a subset of the symptoms in schizophrenia. Therefore, understanding the circuitry within and between the entorhinal cortex and hippocampus is an important endeavor for basic and translational research. This project is aimed to understand the driving sensory modalities of the entorhinal cortex and hippocampus, and to understand the circuitry within and between the two structures. To do this, the firing activity of individual neurons will be recorded while a rat is exploring an environment in virtual reality. Virtual reality is necessary to precisely control the nature and availability of spatially-informative sensory cues. In this design, a change in firing properties i response to a change in a stimulus can be attributed to a strong connection between that sensory modality and the brain region of interest. Further conclusions can be made when considering the differential effects of sensory modalities on the hippocampus and entorhinal cortex. The cell types of interest are hippocampal place cells, which fire in a spatially selectiv fashion; medial entorhinal grid cells, which have spatially periodic fields; medial entorhinal border cells, which fire along the boundaries of an environment; and lateral entorhinal cells, which fire in response to objects within the environment. The aims of this project are to distinguish the relative driving forces of distal visual, self-motion, and proximal cues on the firng of these cell types. In addition, the relationship between two distinct cell types within the media entorhinal cortex will be explored by suppressing the output of border cells and observing the effect on grid cells. Determining the contribution of distinct environmental stimuli on cells in te entorhinal cortex will provide important insights about their formation, as well as how the brain as a whole encodes spatial memories and generates the mental representation of space. Understanding the circuitry in the healthy brain will provide more traction in tackling complex psychiatirc disorders.