Propofol downregulates the activity of glutamatergic neurons in the basal forebrain via affecting intrinsic membrane properties and postsynaptic GABAARs.

Propofol anesthesia rapidly causes loss of consciousness, while the neural mechanism underlying this phenomenon is still unclear. Glutamatergic neurons in the basal forebrain play an important role in initiation and maintenance of wakefulness. Here, we selectively recorded the activity of glutamatergic neurons in vGlut-2-Cre mice. Propofol induced outward currents in a concentration-dependent manner. Bath application of propofol generated membrane hyperpolarization and suppressed the firing rates in these neurons. Propofol-induced stable outward currents persisted after blockade of the action potentials, implying a direct postsynaptic effect of propofol. Furthermore, propofol selectively increased the GABAergic inhibitory synaptic inputs via affecting the GABAARs, but did not affect the glutamatergic transmissions. Together, propofol inhibits the excitability of the glutamatergic neurons via direct influencing the membrane intrinsic properties and the inhibitory synaptic transmission. This inhibitory effect might provide a novel mechanism for the propofol-induced anesthesia.