Memory allocation by CREB. A. CREB is overexpressed in the amygdala by a HSV vector before tone-fear conditioning (training). HSV randomly infects neurons in the amygdala. During training, the memory is allocated to neurons overexpressing CREB (CREB neurons), which results in the preferential induction of Arc expression (neuronal activity marker) in CREB neurons. Controls that did not undergo “learning” (home cage or immediate shock groups) did not show the preferential Arc expression in CREB neurons. B. To directly show the causal link between CREB and memory allocation, CREB neurons were selected for deletion by expression of the diphtheria toxin receptor (DTR). The system utilizes iDTR mice in which DTR expression can be induced by CRE recombinase activity. Therefore, expressing CREB-CRE using a HSV vector makes the neurons susceptible to Diphtheria Toxin (DT). C. Injection of DT after CREB overexpression and the subsequent fear conditioning training ablated CREB expressing neurons that resulted in a loss of the memory.