Temporal dynamics of hippocampal and ventral striatal contributions to spatial memory

The formation of remote memories has been suggested to initially require hippocampal (HPC) activation, followed by a gradual consolidation of memory traces within neocortical networks for long-term storage. However, whether spatial memories permanently depend on the HPC remains debated. Another open question concerns the contribution of subcortical regions such as the ventral striatum (VS), which interacts with the HPC during spatial information processing, but whose role in remote memory has been scarcely investigated. To address these issues, we examined the effects of pre-test manipulations of the HPC and the VS in CD1 mice trained in the Morris water maze (MWM), assessing memory at recent (24h) and remote (30dd) time points. Blockade of AMPA receptors by focal injections of NBQX (0.95 ng/side) into either region impaired recall of the platform location at recent time point (24h), whereas impairment at the remote time point (30dd) was observed only following HPC manipulation. We next assessed the involvement of these regions in the consolidation of remote spatial memories. To this end, two independent groups of mice received viral delivery of either AAV1/2-hSyn::Venus-hM4Di into the VS or AAV5-CaMKIla-hM4Di-mCherry into the HPC. A retention test conducted 30dd after massed MWM training revealed impaired performance in both groups when clozapine-N-oxide (3 mg/kg) was administered immediately after training. Together, these findings suggest a long-lasting role of the HPC in spatial memory storage, whereas the VS appears to play a time-limited role. The VS seems to contribute, similarly to the HPC, to the consolidation of remote memories.