New spatial representations are initially encoded in a labile form by the hippocampus (HPC) and cansubsequently either be lost or stabilized into permanent traces. There is a suggestion that signals originatingfrom the VTA to the HPC play a significant role in this process. We tested the hypothesis that the VTA’sinfluence on memory persistence in the HPC could be modulated by inputs from the ventral striatum (VS).Utilizing transgenic mice expressing a Cre-dependent reporter dTomato, we verified the existence of anindirect pathway from the VS to the HPC via the VTA. For this purpose, we injected AAV1-CRE,possessing anterograde trans-synaptic properties, into the VS. Simultaneously, a second AAV8 for the CRE-dependent expression of the inhibitory DREADD hM4d and the fluorescent reporter mCitrine wasadministered into the VTA. This allowed the identification of VTA neurons receiving direct inputs from theVS projecting to the HPC.Having established this circuit, we investigated whether its inhibition could modulate memory stability inCD1 mice. Employing the same experimental strategy described above to express hM4d in VTA neuronsreceiving VS inputs and projecting to the HPC, we tested the effects of focal HPC administration of CNOimmediately after training in the Morris maze. The inhibition of this circuit significantly impaired mice'sability to locate the platform 24 hours after training. This study underscores a bottom-up modulation ofmemory stability in the HPC by the VS through the VTA, emphasizing the role of the VS in shaping thepersistence of memories.