Circuit structure of cognitive maps in the hippocampus - Project Summary Hippocampus is important for spatial memory. The prototypical neurophysiology is place cells一neurons that are active at particular places in the environment (place fields). Collectively, place cells are thought to form cognitive maps, an internal representation of the environment (i.e. spatial memory). Mechanistic models have made predictions about the pattern of neural connectivity underlying cognitive maps. However, experimental data of circuit structures are difficult to obtain, because neuronal arbors with synapses at nanometer scale are densely packed in neuropils that span a millimeter or more in extent even for local circuits. Volume electron microscopy is currently the only approach that can densely map neural connectivity at synaptic resolution (connectomics). I have been trained in high-throughput transmission electron microscopy (TEM) techniques in PhD, and more recently, I have developed an imaging pipeline with four current fastest TEMs. I will use serial-section TEM imaging followed by circuit reconstruction to map local connectivity in hippocampus. Furthermore, I will combine two-photon calcium imaging of neural activity during spatial navigation and EM reconstruction on the same neurons (functional connectomics), to relate place fields of neurons to the underlying neural circuits in the hippocampus. The goal is to experimentally test long-standing predictions on patterns of neural connectivity by theoretical models: place cells with neighboring place fields are preferentially connected with each other. Towards these goals, in my postdoctoral training I will develop methods to register functionally imaged cells to the same cells in EM-reconstructed volume in the hippocampus and be exposed to deep learning EM reconstruction approach. The training will take place in Princeton Neuroscience Institute, under the guidance of Drs. David Tank and Sebastian Seung. With these skills, my goal is to develop an independent research program of applying functional connectomic methods to relate circuit structure and function in the hippocampus.
