Mouse memory engrams persist after synaptic loss, challenging Hebbian storage model

Researchers used targeted synaptic ablation combined with engram labeling in transgenic mice to sever the Schaffer collateral pathway while tracking labeled memory traces. Behavioral recall of contextual fear conditioning stayed above 70 percent of baseline levels despite confirmed loss of synaptic connectivity, measured via electrophysiology and electron microscopy. This indicates that engram cells can maintain memory information through mechanisms beyond the specific inter-regional synapses thought to encode it. The result extends engram research from labs at MIT and the University of Toronto that first identified sparse populations of neurons sufficient for memory expression. It also aligns with earlier observations that memory traces can survive hippocampal lesions when cortical regions are engaged, suggesting storage redundancy not captured by purely synaptic models of plasticity. Future work must test whether the same dissociation holds in primates and whether alternative molecular or circuit substrates, such as intrinsic excitability changes or neuromodulatory tone, support the residual memory. Human translation will require non-invasive methods to probe engram stability after synaptic disruption.