Striatal involvement in spatial memory depends on the temporal distribution of learning

It has long been known that information presented using spaced repetitions is better remembered than information presented via massed repetitions. However, very little explored are the neurobiological mechanisms that contribute to this phenomenon. To this aim first we compared the effect of spaced and massed training in the Morris Water maze in CD1 mice. Animals trained with the two protocols did not differ in their learning curve or in the ability to remember the platform 24hrs after the last training session, but interestingly only spaced-trained mice could locate the platform 14-day after training. Next, we explored the possibility that the two learning paradigms could involve alternative neural networks. By taking advantage of TetTag mice to label cell ensembles activated by learning and embedded into the memory trace, we showed that striatal and hippocampal activity is highly correlated after spaced but not massed training. Based on this evidence, we started investigating the effects of AMPA receptor blockade in the different component of the striatal complex – i.e. DL and DM striatum - on memory retrieval. Results demonstrate that AMPA receptor activity is required in the DM but not DL striatum for retrieval of spatial information acquired via massed training. Conversely, recall of spatial information acquired via spaced protocol is not affected by manipulation of either component of the striatal complex. Overall, our results demonstrate that striatal circuits involvement in the spatial memory is highly dependent on the temporal distribution of learning. AIM It has long been known that information presented by using spaced repetitions is better remembered than the one presented via massed repetitions. Since the circuits that contribute to this phenomenon are unexplored, we aimed to investigate the possibility that the two learning paradigms might involve different neural networks. METHODS Firstly, we compared the effect of spaced and massed training in the Morris Water maze on learning and memory in CD1 mice. Then, by taking advantage of the TetTag mice, we labeled cell ensembles activated by learning and recruited during the retrieval in hippocampal and striatal regions. Based on our finding, we also investigated the effects of AMPA receptor blockade in the dorsal striatum -i.e. DL and DM striatum - on memory retrieval after the two protocols. RESULTS Animals trained with the two paradigms did not differ in their learning or in the ability to remember the platform 24hrs after the training, but interestingly only spaced-trained mice could locate the platform 14-day thereafter. IEG labeling in the TetTag mice showed that striatal and hippocampal activity is highly correlated after spaced but not massed training. Moreover, pharmacological inhibition of AMPA receptors on CD1 mice demonstrated that DM but not DL striatum is required for retrieval of spatial information acquired via massed training. Conversely, recall of spatial information acquired via spaced protocol is not affected by manipulation of either component of the striatal complex. CONCLUSIONS Overall, our results demonstrate that striatal circuits involvement in the spatial memory is highly dependent on the temporal distribution of learnin