Catecholamine modulation of frontal cortical ignition during wakefulness, sleep and anesthesia

Conscious awareness-diminished during non-rapid-eye-movement (NREM) sleep and general anesthesia-is prevalent during wakefulness, but the underlying mechanism remains poorly understood. Here, we show that activity of catecholamine neurons, known to be higher during wakefulness than NREM sleep, enhances cortical ignition, a process closely associated with conscious awareness. Chemogenetic activation and inactivation of catecholamine neurons, particularly dopaminergic neurons in the ventral tegmental area (VTA), respectively, increased and decreased the amplitude of anterior cingulate area (ACA) excitation evoked by visual cortex (V1) stimulation. Ketamine and isoflurane, two commonly used general anesthetics, greatly reduced V1-to-ACA activity propagation. In addition to suppressing ongoing cortical activity, these general anesthetics significantly reduced the activity of VTA dopaminergic and basal forebrain cholinergic neurons, with dopaminergic activity dropping well below its level during NREM sleep. The strong inhibition of frontal cortical activity evoked by V1 stimulation, prominent during NREM sleep, was also absent under ketamine and isoflurane anesthesia. These results indicate that general anesthesia and NREM sleep suppress global ignition through overlapping but non-identical mechanisms.