Extended fear learning enhances excitatory and inhibitory synaptic transmission onto amygdala engram cells

If a fear engram is too crucial to be ignored, its strength must be amplified to allow it to dominate behavior. Here we report a learning-induced amplification mechanism that promotes an engram to dominance. The amplification mechanism is mediated by CaMKII-dependent increase of the conductance of all AMPA and GABA_A channels in each of the neurons that compose the engram in male mice. Moreover, we show that only crucial fear engrams are amplified and that the amplification mechanism is induced days after training completion. The engram amplification is correlated with intense and enduring freezing response upon retrieval; blocking the amplification dramatically reduces the freezing response. Thus, days after training, engrams that encode crucial information are promoted to dominance through the induction of the amplification mechanism. We introduce a learning functionality in which the strength of a critical engram is biasedly increased, therefore ensuring its dominance of the behavioral response.