Neural mechanism of spatial navigation and memory

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications & trials

Abstract

Our current research projects are centered around two aims: Aim 1. Investigating the neural mechanism underlying spatial representation in the medial entorhinal cortex (MEC). We will harness the cellular-resolution optical tools to test hypotheses of many theoretical models at the microcircuit level, which was previously inaccessible using conventional approaches. Aim 2. Uncovering the circuit and molecular mechanisms of the MEC in the formation, maintenance, and retrieval of spatial memory. We will particularly study the activity, structural and molecular dynamics of the MEC during these processes and investigate the causal link between the MEC dynamics and spatial memory. In the past fiscal year, we made significant progress under the two aims. Under aim 1, we have two projects that focus on the following features of the MEC: (1) encoding of multisensory information in the MEC; (2) functional relationship of different cell types during spatial navigation. For the first project, we studied how different sensory spatial cues are encoded in the MEC during spatial navigation. We have successfully established a multisensory virtual reality (MVR) and revealed sensory-specific activity profiles of different subpopulations of MEC neurons during navigation. Two manuscripts about the MVR technique and the MEC dynamics during the MVR navigation are currently in preparation. For the second project, we have established an experimental pipeline allowing simultaneous imaging of calcium dynamics of different cell types in the MEC during navigation. We aim to continue data collection next year. Under aim 2, we have recently accomplished a big project, in which we combined two-photon imaging, virtual reality behavior, histology, and optogenetics to investigate the cognitive map in the MEC underlying spatial learning and memory. Our study demonstrates the establishment of a consistent cognitive map in the MEC during learning and the causal role of the MEC map in spatial memory. Furthermore, the long-term activity dynamics of grid cells reveal an important circuit mechanism for the formation of a stable grid map during spatial learning. This project is in collaboration with Dr. Joshua Gordon's laboratory at NIMH, and a manuscript describing the above findings will be submitted soon. In another project, we investigate neural dynamics of the MEC underlying spatial learning deficits in an Alzheimers disease mouse model. Finally, we have recently initiated a project in collaboration with the laboratory of Dr. Shen-Ju Chou in Academia Sinica in Taiwan. Our collaboration is focused on understanding the functional property of the ectopic MEC in COUP-TF1 transgenic mice during spatial navigation.