Memories are thought to be encoded by sparsely distributed groups of neurons. However, identifying the precise neurons supporting a given memory (the memory trace) has been a long-standing challenge. We have shown previously that lateral amygdala (LA) neurons with increased cyclic adenosine monophosphate response element-binding protein (CREB) are preferentially activated by fear memory expression, which suggests that they are selectively recruited into the memory trace. We used an inducible diphtheria-toxin strategy to specifically ablate these neurons. Selectively deleting neurons overexpressing CREB (but not a similar portion of random LA neurons) after learning blocked expression of that fear memory. The resulting memory loss was robust and persistent, which suggests that the memory was permanently erased. These results establish a causal link between a specific neuronal subpopulation and memory expression, thereby identifying critical neurons within the memory trace.

amnesia, amygdaloid nucleus, animal cell, animal experiment, article, cell subpopulation, controlled study, cyclic AMP responsive element binding protein, diphtheria toxin, fear, learning, memory, mouse, nerve cell, nervous system, nonhuman, priority journal, protein, protein expression, protein function, subpopulation, toxin,
Erasmus MC: University Medical Center Rotterdam

Han, J.H, Kushner, S.A, Yiu, A.P, Hsiang, H.L, Buch, T, Waisman, A, … Josselyn, S.A. (2009). Selective erasure of a fear memory. Science, 323(5920), 1492–1496. doi:10.1126/science.1164139