Grid Cell Spatial Periodicity: Necessary Intercellular Interactions during Development and Behavioral Function

哺乳动物的空间行为依赖于几个相互连接的大脑区域产生的内部空间表征。一个明显的例子是在内侧内嗅皮层(MEC)。MEC空间表示的主要构件是网格单元，只有当动物的位置对应于等边三角形网格的顶点时，才会触发网格单元。虽然现在已经很好地描述了探索行为中网格细胞的放电过程，但导致网格细胞空间周期性的网络机制以及网格细胞在行为水平上可能发挥的功能尚不清楚。目前的项目有三个主要目标。首先，我们将测试发育早期通过电和化学突触的细胞间相互作用是否在网格细胞空间周期性的形成中发挥重要作用。其次，我们将描述一组表达生长抑素的微血管内皮细胞神经元的活性，并研究它们如何与网格细胞相互作用。再次，我们将检验关于栅格单元空间周期行为函数的主要假设，即栅格单元周期对于路径整合是必不可少的。我们的实验方法将结合时间调控的基因沉默、光遗传学、活体记录和空间导航测试。这项工作将促进我们对MEC空间表示背后的网络机制的理解，并将有助于阐明网格细胞在空间行为中的作用。

Spatial behaviors in mammals depend on internal spatial representations generated in several interconnected brain regions. A striking example is found in the medial entorhinal cortex (MEC). The main building blocks of the MEC spatial representation are grid cells, which fire only when the position of an animal corresponds to the vertices of a grid of equilateral triangles. Although the firing of grid cells during exploratory behavior is now well characterized, the network mechanisms responsible for the spatial periodicity of grid cells and the possible function of grid cells at the behavioral level are not known. The current project has three main objectives. Firstly, we will test whether intercellular interactions via electrical and chemical synapses early during development play an important role in the formation of grid cell spatial periodicity. Secondly, we will characterize the activity of a group of MEC neurons expressing somatostatin and investigate how they interact with grid cells. Thirdly, we will test the main hypothesis regarding the behavioral function of grid cell spatial periodicity, namely, that grid cell periodicity is essential for path integration. Our experimental approach will combine temporally-regulated gene silencing, optogenetics, in vivo recordings and spatial navigation tests. This work will advance our understanding of the network mechanisms behind the spatial representation of the MEC and will help to clarify the role of grid cells in spatial behavior.