The emerging role of the parabrachial complex in the generation of wakefulness drive and its implication for respiratory control

• Recent data suggesting a role for the parabrachial complex in arousal.
• Lesion of the parabrachial complex triggers coma.
• Glutamatergic parabrachial projections to basal forebrain and hypothalamus maintain wakefulness.
• Breathing control via parabrachial circuits is also linked to wakefulness.

The parabrachial complex is classically seen as a major neural knot that transmits viscero- and somatosensory information toward the limbic and thalamic forebrain. In the present review we summarize recent findings that imply an emerging role of the parabrachial complex as an integral part of the ascending reticular arousal system, which promotes wakefulness and cortical activation. The ascending parabrachial projections that target wake-promoting hypothalamic areas and the basal forebrain are largely glutamatergic. Such fast synaptic transmission could be even more significant in promoting wakefulness and its characteristic pattern of cortical activation than the cholinergic or mono-aminergic ascending pathways that have been emphasized extensively in the past. A similar role of the parabrachial complex could also apply for its more established function in control of breathing. Here the parabrachial respiratory neurons may modulate and adapt breathing via the control of respiratory phase transition and upper airway patency, particularly during respiratory and non-respiratory behavior associated with wakefulness.