Altered spines on memory-encoding neurons in the hippocampus

25 February 2025

A study performed by PhD student Panthea Nemat of the Molecular Engrams team led by Dr. Priyanka Rao-Ruiz was recently published in a special issue on “Deciphering the memory engram” in Neurobiology of Learning and Memory in which they describe “Structural synaptic signatures of contextual memory retrieval-reactivated hippocampal engram cells”.

The article can be found here:

https://www.sciencedirect.com/science/article/pii/S1074742725000140?via%3Dihub

In this article, the authors performed closer investigation of so-called engram cells which are thought to harbor the physical representation of memories. While numerous engram cells across the brain are activated during memory formation, only a subset is reactivated during recall. In this project, the authors investigated whether structural synaptic connectivity of these reactivated and non-reactivated engram cells differs in the hippocampus and whether this is dependent on the context valence. To achieve this, a novel analysis pipeline was developed that enables semi-automatic reconstruction of spines and dendrites based on fluorescent labelling of engram cells. The pipeline also integrates multilevel statistical analyses to account for the nested data structure. The authors found that at the level of excitatory CA3 to CA1 engram cells, structural synaptic connectivity of CA1 engram cells is influenced by contextual valence, reactivation status of an engram cell, or a combination thereof. Specifically, parameters related to the number, distribution, and morphology of CA1 engram cell synapses vary based on these factors. These findings give first indications that engram cells follow distinct pathways in structural synaptic connectivity, which may be essential for refining and sustaining engram networks over time.

The analysis pipeline is accessible on GitHub under the following link:

https://github.com/PantheaNemat/structural_dendrite_spine_analysis