Behavioral Enhancement of Associative Learning Requires Overlapping Neuronal Populations

A weak memory can be converted into a long-term form if it is preceded by another weak training episode or exploration of a new environment. Current hypotheses explain the mechanisms behind this phenomenon, suggesting that the formation of new memories involves a population of neurons that are pre-activated by previous cognitive experiences. We visualized neuronal activity from two distinct cognitive episodes separated in time using transgenic Arc-Cre-Tomato mice. Mice were trained using a weak cued fear conditioning protocol that typically does not lead to long-term memory formation. However, when re-trained with the same cue, significant memory improvement was observed. In contrast, different cues did not produce this effect. Our analysis revealed a higher percentage of overlapping neuronal populations in the prelimbic cortex, primary auditory cortex, and amygdala in mice trained with the same cue. These findings suggest that cumulative learning and memory potentiation depend on the involvement of overlapping neuronal populations and only occur when these events engage the same groups of brain neurons.