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Cryo-electron Microscopy

Cryo-electron Microscopy

Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...

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Related Experiment Video

Updated: Jan 11, 2026

Preparation of Primary Neurons for Visualizing Neurites in a Frozen-hydrated State Using Cryo-Electron Tomography

Preparation of Primary Neurons for Visualizing Neurites in a Frozen-hydrated State Using Cryo-Electron Tomography

Published on: February 12, 2014

Memory engram synapse 3D macromolecular architecture visualized by cryoCLEM-guided cryoET.

Charlie Lovatt¹, Thomas O'Sullivan¹, Clara Ortega-de San Luis²

¹Astbury Centre for Structural Biology, School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.

Structure (London, England : 1993)

|November 15, 2025

Summary

Scientists visualized the 3D structure of memory engram synapses in the mouse hippocampus. This reveals diverse molecular organization within these memory-storing neuronal connections, offering insights into memory formation.

Keywords:

Engram Memory cryo-CLEM cryo-ET cryo-electron tomography in-tissue structure synapse

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Published on: January 9, 2015

Flash-and-Freeze: A Novel Technique to Capture Membrane Dynamics with Electron Microscopy

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Published on: May 1, 2017

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Last Updated: Jan 11, 2026

Preparation of Primary Neurons for Visualizing Neurites in a Frozen-hydrated State Using Cryo-Electron Tomography

Preparation of Primary Neurons for Visualizing Neurites in a Frozen-hydrated State Using Cryo-Electron Tomography

Published on: February 12, 2014

Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction

Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction

Published on: January 9, 2015

Flash-and-Freeze: A Novel Technique to Capture Membrane Dynamics with Electron Microscopy

Flash-and-Freeze: A Novel Technique to Capture Membrane Dynamics with Electron Microscopy

Published on: May 1, 2017

Area of Science:

Neuroscience
Structural Biology
Molecular Biology

Background:

Memory storage involves physicochemical changes in engram cells, forming neuroanatomical circuits modified by experience.
Learning alters synaptic communication to rewire engram circuits, but the macromolecular organization within these synapses remains unclear.

Purpose of the Study:

To visualize the in-tissue 3D macromolecular architecture of engram synapses associated with contextual fear memory in the mouse hippocampus.
To investigate the structural diversity of macromolecules and organelles within engram synapses.

Main Methods:

Development and application of engram labeling technology.
Utilizing cryogenic correlated light and electron microscopy (cryoCLEM)-guided cryogenic electron tomography (cryoET).
Combining in vivo functional neuroscience with structural biology techniques.

Main Results:

Engram synapses display significant structural diversity in both pre- and postsynaptic compartments and the synaptic cleft.
Observed variations include differences in membrane proteins, synaptic vesicle occupancy, and F-actin copy number.
Detailed 3D macromolecular organization of engram synapses was successfully visualized.

Conclusions:

The study provides a novel methodological framework, termed "engram to tomogram," for studying memory engrams.
This approach enables testing fundamental molecular plasticity mechanisms within engram circuits.
Reveals structural heterogeneity at the molecular level within memory-associated synapses.