Imaging excitatory synaptic input to hippocampal dendritic segments during spatial navigation

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Imaging excitatory synaptic input to hippocampal dendritic segments during spatial navigation Heydar Davoudi, Department of Neurobiology, Northwestern University Project Summary/Abstract The hippocampus has a critical role in spatial navigation and formation of episodic memories. Hippocampal output area CA1 is crucial for spatial learning and memory and it receives major excitatory inputs from entorhinal cortex (EC) through the Perforant pathway (PP) and from hippocampal areas CA2 and CA3 through the Schaffer collateral (SC) pathways. During exploration, a rodent’s CA1 neurons show location-specific activity known as place fields of these “place cells”. CA1 place fields may be driven by PP and SC input pathways arriving on CA1 dendritic spines. However, it is unknown what different roles these two pathways play in driving the CA1 place cell activity necessary for spatial learning and memory. Here, I propose to develop a previously-unattainable simultaneous dual-color two-photon functional imaging of a CA1 place cell soma and its synaptic-scale excitatory input in head-fixed mice navigating through a virtual-reality environment. I aim to develop microprism-based and Bessel beam-based two-photon microscopies to image a CA1 place cell soma and the synaptic-scale excitatory input to its basal and distal tuft dendritic segments, which respectively receive inputs from SC and PP pathways. This allows me to determine how the different excitatory synaptic inputs carried by these two pathways differentially contribute to somatic place fields in a familiar track and during learning a new virtual environment. Altogether, this proposal aims to add to our understanding of synaptic- level cognitive processing which is disrupted in neurological and psychiatric diseases such as Alzheimer’s disease and schizophrenia.