Ventral striatum control of spatial memory consolidation in the hippocampus

New memory traces are initially encoded in the hippocampus (HPC) in an unstable form, and only a subset is consolidated into long-term memory, suggesting the existence of mechanisms that select which information is stabilized. Reward-related signals from the ventral striatum (VS) are proposed to contribute to this process. To investigate this hypothesis, we injected AAV1-hSyn-Cre, an anterograde trans-synaptic viral vector, into the VS of transgenic mice expressing a Cre-dependent reporter. In parallel, a second Cre-dependent AAV expressing EGFP was delivered into the ventral tegmental area (VTA). This approach enabled visualization of EGFP-positive fibers in the dorsal HPC (dHPC) originating from VTA neurons directly receiving VS inputs, thereby identifying a VS–VTA–HPC pathway. To assess the functional relevance of this circuit in memory consolidation, we expressed a Cre-dependent inhibitory DREADD selectively in VTA neurons receiving VS projections. The projections of these neurons were inhibited by CNO into the dHPC of CD1 mice immediately after a massed training protocol of the Morris Water Maze. This manipulation significantly impaired the animals’ ability to locate the hidden platform at both 24 hours and 30 days after training, indicating deficits in recent and remote memory consolidation. Overall, these findings identify a VS–VTA–HPC circuit that regulates memory persistence and highlight the ventral striatum as a key structure influencing memory persistence through bottom-up modulation of hippocampal activity. Ongoing experiments aim to assess dendritic spine density in the dHPC as a measure of learning-induced plasticity and to determine the neurochemical basis this pathway.