Ventral tegmental area glutamatergic neurons suppress hippocampal ripples and induce head movements in mice

Ripples are brief, high-frequency hippocampal oscillations crucial for memory consolidation, occurring predominantly during 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 ripples 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 occurrence. Selective activation of retrogradely labeled hippocampus-projecting VTA glutamatergic neurons also suppressed ripples. In contrast, activation of GABAergic (vGAT+) neurons produced nonsignificant suppression, and activation of dopaminergic (DAT+) neurons showed no effect. During glutamatergic activation, we observed small, consistent head movements. Trial-by-trial analysis revealed no correlation between head movement and ripple suppression. Furthermore, activation of VTA glutamatergic neurons during wakefulness also led to head movement, suggesting that ripple suppression and head movement could be dissociated. These results suggest that VTA vGlut2 + neurons may play a role in head movement and that their activation suppresses hippocampal ripples, offering a potential way to alter memory consolidation.