GABAergic ventrolateral pre-optic nucleus neurons are involved in the mediation of the anesthetic hypnosis induced by propofol

Abstract

Intravenous anesthetics have been used clinically to induce unconsciousness for seventeen decades, however the mechanism of anesthetic-induced unconsciousness remains to be fully elucidated. It has previously been demonstrated that anesthetics exert sedative effects by acting on endogenous sleep-arousal circuits. However, few studies focus on the ventrolateral pre-optic (VLPO) to locus coeruleus (LC) sleep-arousal pathway. The present study aimed to investigate if VLPO is involved in unconsciousness induced by propofol. The present study additionally investigated if the inhibitory effect of propofol on LC neurons was mediated by activating VLPO neurons. Microinjection, target lesion and extracellular single-unit recordings were used to study the role of the VLPO-LC pathway in propofol anesthesia. The results demonstrated that GABAA agonist (THIP) or GABAA antagonist (gabazine) microinjections into VLPO altered the time of loss of righting reflex and the time of recovery of righting reflex. Furthermore, propofol suppressed the spontaneous firing activity of LC noradrenergic neurons. There was no significant difference observed in firing activity between VLPO sham lesion and VLPO lesion rats. The findings indicate that VLPO neurons are important in propofol-induced unconsciousness, however are unlikely to contribute to the inhibitory effect of propofol on LC spontaneous firing activity.

Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABAA receptors

“…In addition, it contains diverse neuronal types, including cholinergic, glutamatergic, parvalbumin-positive (PV + ) GABAergic and somatostatin-positive (SOM + ) GABAergic neurons [15]. The cholinergic, glutamatergic and PV + GABAergic neurons are wakefulness-promoting neurons [16,17], while the SOM + GABAergic neurons are sleep-promoting neurons [18,19].…”

The Sleep-Promoting Ventrolateral Preoptic Nucleus: What Have We Learned over the Past 25 Years?

“…Metabolic Sensor : Glucose infusion into the VLPO region promotes NREM sleep [ 108 ]. Anesthesia : Activation of VLPO neurons [ 63 , 69 , 119 , 120 ]; Manipulation(s) of VLPO neurons alter anesthesia [ 63 , 69 , 134 ] or have no effect on anesthesia [ 16 , 52 ]. …”

“…Manipulation(s) of VLPO neurons alter anesthesia [ 63 , 69 , 134 ] or have no effect on anesthesia [ 16 , 52 ].…”

“…• Activation of VLPO neurons [63,69,119,120]; • Manipulation(s) of VLPO neurons alter anesthesia [63,69,134] or have no effect on anesthesia [16,52].…”

Neural Substrates for the Regulation of Sleep and General Anesthesia

“…Isoflurane directly activates VLPO neurons in vitro , and propofol anesthesia or pentobarbital at a sedative dose significantly increases the expression of c-Fos in VLPO neurons [ 11 ]. Local administration of GABA receptor agonists in VLPO shortens the propofol-induced LORR and prolongs the RORR [ 12 ]. It has been observed that selective knockout of the vesicular GABA transporter gene ( vgat ) in the POA slowed the transition to sedation immediately after dexmedetomidine administration, but the mice were sedated 30 min after injection; this indicates that POA GABAergic neurons were necessary for the rapid induction of dexmedetomidine sedation but not sedative maintenance [ 13 ].…”