Paraventricular thalamus controls consciousness transitions during propofol anaesthesia in mice

Background: The neuronal mechanisms underlying propofol-induced modulation of consciousness are poorly under-stood. Neuroimaging studies suggest a potential role for non-specific thalamic nuclei in propofol-induced loss of con-sciousness. We investigated the contribution of the paraventricular thalamus (PVT), a midline thalamic nucleus that has been implicated in arousal control and general anaesthesia with inhaled anaesthetics, to loss and recovery of con-sciousness during propofol anaesthesia.Methods: Polysomnographic recordings and righting reflex test were used to determine the transitions of loss and re-covery of righting reflex, used as a measure of consciousness in mice, during propofol anaesthesia in mice under con-ditions mimicking clinical propofol administration. PVT neuronal activities were monitored using fibre photometry and regulated using optogenetic and chemogenetic methods.Results: Population activities of PVT glutamatergic neurones began to decrease before propofol-induced loss of con-sciousness and rapidly increased to a peak at the onset of recovery of consciousness. Chemogenetic inhibition of PVT calretinin-expressing (PVTCR) neurones shortened onset (from 176 [35] to 127 [26] s; P=0.001) and prolonged return (from 1568 [611] to 3126 [1616] s; P=0.002) of righting reflex. Conversely, chemogenetic activation of PVTCR neurones exerted opposite effects. Furthermore, optogenetic silencing of PVTCR neurones accelerated transitions to loss of consciousness (from 205 [35] to 158 [44] s; P=0.027) and slowed transitions to recovery of consciousness (from 230 [78] to 370 [99] s; P=0.041). During a steady period of unconsciousness maintained with continuous propofol infusion, brief optical acti-vation of PVTCR neurones restored cortical activity and arousal with a latency of about 5 s.Conclusions: The paraventricular thalamus contributes to the control of consciousness transitions in propofol anaes-thesia in mice. This provides a potential neuroanatomical target for controlling consciousness to reduce anaesthetic dose requirements and side effects.

Automated summary

This study found that the activity of the paraventricular thalamus (PVT) is closely related to consciousness transitions during propofol anesthesia. Inhibition of PVT neurons promotes the loss and recovery of consciousness, while stimulation of PVT neurons has the opposite effect. The results provide a potential neuroanatomical target for controlling consciousness to reduce anesthesia dose requirements and side effects.