Ventral Tegmental Area Glutamatergic Neurons Suppress Hippocampal Sharp-wave Ripples and Induce Head Movements in Mice

Abstract

Sharp-wave ripples are brief, high-frequency hippocampal oscillations crucial for memory consolidation, occurring predominantly during the non-rapid-eye-movement (NREM) sleep. While ripples are generated intrinsically within the hippocampus, growing evidence suggests that their occurrence is modulated by subcortical regions. Whether the ventral tegmental area (VTA)--a subcortical region that directly projects to the hippocampus--regulates ripple activity remains unknown. To investigate this, we optogenetically activated VTA neurons during NREM sleep and recorded ripple activity in the dorsal hippocampus via field recording electrodes. Using cell-type specific excitatory opsin expression in the VTA, we found that activation of glutamatergic (vGlut2+) neurons strongly suppressed ripple incidence. In contrast, activation of GABAergic (vGAT+) neurons produced weak suppression, and activation of dopaminergic (DAT+) neurons showed no effect. During ripple suppression by glutamatergic activation, we observed small but consistent head movements. Trial-by-trial analysis revealed no correlation between head movement and ripple suppression. Furthermore, glutamatergic activation during wakefulness also led to head movement, suggesting that ripple suppression and head movement could be dissociated. Overall, our results suggest that VTA vGlut2+ neurons play a role in head movement and that their activation suppresses hippocampal sharp-wave ripples during NREM sleep, offering a potential way to alter memory consolidation.