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Updated: May 17, 2026

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Post-embedding Immunogold Labeling of Synaptic Proteins in Hippocampal Slice Cultures
Published on: April 3, 2013
GRASPing experience-dependent protein expression signatures enriched for hippocampal engram cell synapses
Biswajit Moharana1, Panthea Nemat1, Renee M Pullen1
1Dept. of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Science Advances
|May 15, 2026
Summary
This study reveals how synaptic proteins change in hippocampal CA1 engram cells after learning. Aversive memories alter postsynaptic proteins, while neutral memories affect presynaptic proteins, offering insights into memory formation.
Area of Science:
- Neuroscience
- Molecular Biology
- Proteomics
Background:
- Synaptic plasticity in memory engram cells is crucial for memory storage and recall.
- Negative memories are often more salient than neutral ones.
- The protein-level changes at specific synapses within memory engram cells are not well understood.
Purpose of the Study:
- To investigate the proteomic differences in CA1 engram cell synapses after neutral versus aversive contextual learning.
- To identify protein signatures related to synapse structure, efficacy, and strength in memory engram cells.
Main Methods:
- Utilized spatiotemporally restricted synapse labeling, sorting, and mass spectrometry.
- Generated a proteomic dataset from CA1 engram cell synapses receiving CA3 input 72 hours post-learning.
- Performed differential analysis against an unlabeled comparator group.
Main Results:
- Identified distinct protein expression signatures in CA1 engram cell synapses following learning.
- Aversive learning predominantly induced postsynaptic protein changes.
- Neutral context exploration skewed proteomic changes toward presynaptic components.
- The differential proteome was enriched for genes associated with cognitive traits and disorders.
Conclusions:
- Synaptic proteome adaptations differ between aversive and neutral contextual memory recall.
- These findings provide a resource for understanding the molecular basis of contextual memory at the synapse.
- Highlights the role of specific protein changes in memory salience and formation.

