Memory Engram Cells Retain Memory Under Retrograde Amnesia

This work outlines circuitry involved in memory formation using a dual genetic reporter system for labeling learning-dependent cells, a mouse model of contextual fear learning and delivery of an amnestic agent. The authors determine that if an amnestic agent is given shortly after the conditioning shock, the animals behave as though they had never experienced the shock (do not freeze when a tone is administered in a cage) and have neurons in the circuit with decreased synaptic strength and spine density. But, optogenetic activation of the circuits that were active during (specific) memory formation causes the mouse to freeze (as though it remembered the shock). Therefore, although the memory of the fearful event (tone-shock) is established even if an amnestic agent is given, the ability to access the memory (recall) seems to be the inhibited process. The authors propose that intact neuronal connectivity patterns are important for memory formation and that synaptic strength may be involved in memory retrieval.