PVN oxytocin - VTA neurocircuit modulate the emergence of general anesthesia induced by isoflurane in mice.

AIMS: The paraventricular nucleus of the hypothalamus (PVN) plays a pivotal role in regulating consciousness transition, in which oxytocin neurons (OXT) are involved. The ventral tegmental area (VTA) is one of the important projection regions of the PVNOXT, closely related to the transition of anesthesia status. However, whether oxytocin neurons in the PVN and PVNOXT-VTA pathway contribute to isoflurane-induced anesthetic state transitions is unknown.

METHODS

Immunostaining and fiber photometry were used to verify the neuronal activity during the isoflurane anesthesia. Chemogenetic or optogenetic stimulation of PVN OXT neurons was then performed to verify their role in anesthesia, along with electroencephalography and behavioral recording.

RESULTS

We found that isoflurane decreased the activity of PVN oxytocin neurons. Then, activation of PVN oxytocin neurons caused a reduction of the anesthesia emergence time with an increase in arousal-related power. Optogenetic inhibition of PVN oxytocin neurons caused a more isoflurane anesthesia recovery time along with an increase in low-frequency power. Similarly, activation or inhibition of PVNOXT-VTA neural pathway produced similar effects.

CONCLUSIONS

Collectively, oxytocin neurons in the PVN certainly modulate isoflurane anesthesia, in which the PVNOXT-VTA pathway plays a significant and unique part.