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Updated: Jul 16, 2025

A Tissue Clearing Method for Neuronal Imaging from Mesoscopic to Microscopic Scales
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Tissue clearing applications in memory engram research.

Kwok Yui Tony Yip1, Johannes Gräff1

  • 1Laboratory of Neuroepigenetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Frontiers in Behavioral Neuroscience
|September 13, 2023
PubMed
Summary

Brain-wide mapping of memory engrams is now possible using advanced tissue clearing and microscopy. This allows visualization of the "engram complex" across the whole brain, revealing circuit connectivity and molecular details.

Keywords:
engram compleximmunolabeling-enabled three-dimensional imaging of solvent-cleared organsmemory engramneuroepigeneticsneuronal circuittissue clearing

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Systems Biology

Background:

  • Memory engrams, the physical basis of memory traces, are neuronal ensembles activated during learning.
  • The concept of an
  • engram complex
  • postulates interconnected engram cells across brain regions for memory storage.
  • Previous technical limitations hindered whole-brain visualization of these complexes.

Purpose of the Study:

  • To review brain-wide engram mapping studies.
  • To provide a guide for tissue clearing techniques in engram research.
  • To highlight the potential of new technologies for studying memory engrams.

Main Methods:

  • Tissue clearing techniques
  • Advanced light-sheet microscopy
  • Automated 3D image analysis
  • Whole-brain multiplexed immunostaining for engram reactivation

Main Results:

  • Recent technological advancements enable brain-wide mapping of engram cells.
  • Visualization of the
  • engram complex
  • across the entire brain is now feasible.
  • Tissue clearing facilitates simultaneous analysis of engram cell circuit connectivity and molecular characteristics.

Conclusions:

  • Tissue clearing, microscopy, and image analysis revolutionize engram research.
  • These methods allow for the identification of novel brain regions and circuits involved in memory storage.
  • The
  • engram complex
  • can now be robustly examined for its role in memory.