Contribution of Multisensory Stimuli on Entorhinal Circuit Dynamics and the Menta

描述(申请人提供)：一些神经和精神疾病，包括阿尔茨海默氏症和精神分裂症，显示出空间记忆任务的缺陷。不足为奇的是，同样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。内嗅觉皮质整合了所有感觉模式的信息，然后将这些信息传递到海马体，在那里形成了认知地图。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联：导致阿尔茨海默氏症跨突触传播的tau蛋白，以及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体内部和之间的回路是基础研究和翻译研究的重要努力。该项目旨在了解内嗅觉皮质和海马体的驱动感觉模式，并了解这两个结构内部和之间的回路。要做到这一点，当老鼠在虚拟现实中探索环境时，将记录下单个神经元的放电活动。为了精确控制空间信息感官线索的性质和可用性，虚拟现实是必要的。在这个设计中，对刺激变化反应的放电特性的变化可以归因于感觉通道和大脑感兴趣区域之间的强烈联系。当考虑到感觉方式对海马体和内嗅觉皮质的不同影响时，可以得出进一步的结论。感兴趣的细胞类型是海马区细胞，它以空间选择性的方式放电；内侧内嗅网细胞，它有空间周期性的场；内侧内嗅觉边缘细胞，它沿着环境的边界放电；以及外侧内嗅觉细胞，它对环境中的物体做出反应而放电。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相对驱动力。此外，还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间内嗅觉皮质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为它们的形成以及大脑作为一个整体如何编码空间记忆和产生空间的心理表征提供重要的见解。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.