Orexinergic system in the locus coeruleus modulates the CO2 ventilatory response

Area of Science:

• Neuroscience
• Respiratory Physiology

Background:

• Orexins are hypothalamic neuropeptides regulating sleep-wake states and chemoreception.
• The locus coeruleus (LC) is a key chemosensitive site expressing orexin receptor 1 (OX1R).

Purpose of the Study:

• To investigate the role of OX1Rs in the LC on the ventilatory response to hypercapnia.
• To determine if this role is dependent on vigilance state and diurnal cycle.

Main Methods:

• Unilateral injections of an OX1R antagonist (SB-334867) into the LC of male Wistar rats.
• Evaluation of ventilatory response to 7% CO2 during wakefulness and sleep in both dark and light phases.

Main Results:

• Hypercapnia increased ventilation in all groups.
• SB-334867 attenuated the hypercapnic chemoreflex during wakefulness in the dark phase, but not in the light phase or during sleep.
• This attenuation was linked to changes in tidal volume.

Conclusions:

• Projections of orexin-containing neurons to the LC, acting via OX1Rs, contribute to the hypercapnic chemoreflex.
• This contribution is specifically observed during wakefulness in the dark phase of the diurnal cycle.