Sensory stimulation triggers different spike responses in serotonin and dopamine neurons in the dorsal midbrain tegmentum

Abstract The dorsal midbrain tegmentum, including the dorsal raphe nucleus (DRN) and the ventrolateral periaqueductal gray (vlPAG), contains diverse neuronal populations. Within this region, serotonin (5-HT) and dopamine (DA) neurons are the principal monoaminergic cell types and exert widespread influence on brain circuits. While the role of 5-HT and DA neurons in sensory integration is well established, their stimulus-driven spiking activity remains incompletely characterized. Using silicon probe recordings in mice, we found that >57% of DRN/vlPAG neurons responded to foot shock and mechanical stimulation, whereas <15% showed changes in spiking activity following light or acoustic stimulation. At the population level, similar results were obtained using juxtacellular recordings, a method that allowed post hoc identification of 5-HT and DA neurons. Upon foot shock delivery, 5-HT neurons exhibited heterogeneous responses, including both excitation and inhibition, whereas DA neurons typically increased their firing rates. We found that DA neurons lacking vasoactive intestinal polypeptide (VIP) fired within the first second after foot shocks, while VIP-expressing DA neurons were most active later. Together, our results demonstrate that DRN/vlPAG neurons are most responsive to foot shock and mechanical stimuli. Moreover, 5-HT and DA neurons exhibit distinct patterns of activation following aversive inputs, suggesting that they play different roles in sensory information processing.