Neural mechanism of spatial navigation and memory

National Institute Of Neurological Disorders And Stroke

Investigators

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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 harness the cellular-resolution optical tools to test the 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 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 three 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. (3) Encoding of visual-spatial cues by the MEC neural population. 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 the MEC map during navigation. The manuscripts about this story will be submitted soon. 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. In the last project, we studied how visual cues with different features are represented by the population code of the MEC. Under aim 2, we have been conducting four projects. In the first project, 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 necessity of the MEC map in spatial memory. This project is in collaboration with Dr. Joshua Gordon's laboratory at NIMH, and a manuscript describing the above findings is currently under review. In the second project, we have been collaborating with Dr. Ila Fietes laboratory at MIT to investigate how environmental features shape the grid cell activity during spatial learning. In addition, we are also collaborating with Dr. Veronica Alvarezs laboratory to investigate the synaptic plasticity of the MEC during spatial learning. In the last project, we examine neural dynamics of the MEC underlying spatial learning deficits in an Alzheimer's disease mouse model. Finally, we have recently completed 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.