A Brainstem-Thalamic-Cortex Glutamatergic Neuron Pathway Modulates Propofol Anesthesia.

Background: The precise mechanisms underlying the modulation and transformation of consciousness during propofol anesthesia remain inadequately understood. Both the paraventricular thalamus (PVT)-medial prefrontal cortex (mPFC) pathway and the parabrachial nucleus (PB) are implicated in the regulation of sleep-wake cycles. Consequently, this study aimed to explore whether projections from the PB to the PVT-mPFC pathway are involved in the effects of propofol anesthesia. Methods: Anterograde and retrograde viral tracing techniques were employed to map the projections from the PB to the PVT and from the PVT to the mPFC. The activity within this pathway was monitored using fiber photometry during propofol anesthesia. The study further examined the role of this pathway during the induction and emergence phases of propofol anesthesia through optogenetic modulation in conjunction with cortical electroencephalography (EEG) recordings. Results: Glutamatergic neurons in the PB exhibit dense projections to the PVT, and in turn, PVT glutamatergic neurons project densely to the mPFC. Administration of propofol resulted in a reduction of calcium signals in the parabrachial glutamatergic nucleus to paraventricular thalamus (PB Conclusion: Collectively, this study provides supportive evidence for the involvement of a brainstem-thalamic-cortical glutamatergic circuit in propofol anesthesia. The findings offer a preliminary perspective on how propofol may modulate consciousness and highlight potential pathways worthy of further investigation.