The cellular mechanisms underlying the sedative effect of general anesthetics are not completely understood. Accumulating evidence indicates that the ventrolateral preoptic area (VLPO) of the hypothalamus plays a critical role. The VLPO contains 2 major types of neurons, the noradrenalin-inhibited GABAergic projecting neurons (NA(−) neurons) and the noradrenalin-excited interneurons (NA(+) neurons) which are probably also γ-aminobutyric acid (GABA)-containing neurons. Our previous work suggests that NA(−) neurons are normally under the inhibitory control of NA(+) neurons. Previous studies also show that GABAergic agents including propofol activate GABAergic projecting neurons in the VLPO, which is believed to lead to the inhibition of the arousal-producing nuclei in the tuberomammillary nucleus and sedation. However, how propofol activates VLPO neurons remains unclear. We explored the possibility that propofol activates NA(−) neurons indirectly, by inhibiting GABAergic transmission including those from VLPO NA(+) neurons.METHODS:
Electrophysiological activities were recorded from VLPO cells in acute brain slices of rats.RESULTS:
Propofol facilitates the discharges of NA(−) neurons and reduces the frequency, but not the amplitude of spontaneous GABAergic inhibitory postsynaptic currents in NA(−) neurons. Conversely, propofol suppressed the discharges of NA(+) neurons.CONCLUSION:
Propofol excites VLPO NA(−) neurons by reducing GABAergic transmission, at least in part by inhibiting VLPO NA(+) neurons. This may be a critical mechanism contributing to propofol-induced sedation.