The neural substrate of spatial memory stabilization depends on the distribution of the training sessions

Distributed training is known to lead to more robust memory formation as compared to training experiences with short intervals. Although this phenomenon, termed distributed practice effect, ubiquitous over a wide variety of tasks and organisms, has long been known by psychologists, its neurobiological underpinning is still poorly understood. Using the striatum as a model system here we tested the hypothesis that the ability of distributed training to optimize memory might depend upon the recruitment of different neural substrates compared to those engaged by massed training. First, by contrasting the medial and the lateral domains of the dorsal striatum after massed and distributed training we demonstrated that neuronal activity, as assessed using c-Fos expression, is differentially affected by the training protocol in the two striatal subregions. Next, by blocking the AMPA receptors before recall we provide evidence to support a selective role of the medial and the lateral striatum in the storage of information acquired by massed and distributed training, respectively. Finally, we found that optogenetic stimulation of the dorsolateral striatum during massed training enables the formation of an enduring memory similar to what is observed with distributed learning. Overall, these findings identify a possible mechanism for the distributed practice effect, a still poorly understood aspect of learning.