NEURO2026

Chairperson: Yasuhiko Sato (Carl Zeiss Co., Ltd.)

Co-hosted by Carl Zeiss Co., Ltd.

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 “time axis” 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—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.