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Lectures in Japanese

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Visualizing Activity History with CLEM: Spatiotemporal Structural Analysis of Memory Engram Synapses

Electron microscopy (EM) enables nanoscale analysis of neural ultrastructure, but the obtained information is inherently limited to a static snapshot at the time of tissue fixation. In this presentation, I will introduce a new correlative light and electron microscopy (CLEM) approach that incorporates a &ldquo;time axis&rdquo; into EM analysis by combining ultrastructural imaging with activity-history-dependent labeling. Using cFos-tTA mice together with the eGRASP system, we fluorescently labeled synapses formed between hippocampal engram cells activated during memory acquisition. These labeled synapses were first imaged as three-dimensional confocal z-stacks, followed by near-infrared branding (NIRB) using a two-photon laser to define regions of interest for serial block-face electron microscopy (SBEM). By tracing engram dendrites within the EM volume, we identified engram-to-engram synapses that were specifically formed during memory encoding. This approach enables ultrastructural analysis while preserving information about the past neural activity and experience associated with individual synaptic structures&mdash;information that is normally lost in conventional EM workflows. By integrating functional history with nanoscale anatomy, this strategy provides a new framework for studying activity-dependent circuit remodeling, memory engrams, and synaptic plasticity.

NEURO2026

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[2LS09-02]Visualizing Activity History with CLEM: Spatiotemporal Structural Analysis of Memory Engram Synapses

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