Striatal neurones expressing D1 dopamine receptors modulate consciousness in sevoflurane but not propofol anaesthesia in mice.

Summary

In mice, dorsal striatal D1 receptor neurons decreased activity before sevoflurane-induced LOC and recovered after emergence. Optogenetic activation triggered recovery of consciousness and cortical activation during steady sevoflurane anesthesia, while chemogenetic inhibition accelerated induction and delayed emergence; these manipulations had no effect under propofol. Findings indicate anesthetic-specific modulation of arousal circuitry.

Key Findings

• Population activity of striatal D1R neurons decreased before LOC and recovered after ROC under sevoflurane.
• Optogenetic activation induced ROC and cortical activation during steady-state sevoflurane anesthesia; chemogenetic inhibition accelerated induction (242.0→194.0 s, P=0.010) and delayed emergence (93.5→133.5 s, P=0.005).
• Chemogenetic activation accelerated emergence (107→81.3 s, P=0.011).
• No opto/chemogenetic effects were observed under propofol anesthesia.

Clinical Implications

Although preclinical, the results suggest potential for targeted neuromodulation to hasten emergence from volatile anesthesia and highlight that mechanisms of unconsciousness differ between agents.

Limitations

• Mouse model limits direct clinical translatability.
• Exact sample sizes and sex distribution are not specified in the abstract.

Future Directions

Test whether noninvasive neuromodulation targeting basal ganglia expedites emergence from volatile anesthesia in humans and map downstream circuits differentiating volatile vs i.v. agents.