Respiration and autonomic regulation and orexin

Abstract

Orexin, a small neuropeptide released from neurons in the hypothalamus with widespread projections throughout the central nervous system, has broad biological roles including the modulation of breathing and autonomic function. That orexin activity is fundamentally dependent on sleep-wake state and circadian cycle requires consideration of orexin function in physiological control systems in respect to these two state-related activity patterns. Both transgenic mouse studies and focal orexin receptor antagonism support a role for orexins in respiratory chemosensitivity to CO2 predominantly in wakefulness, with further observations limiting this role to the dark period. In addition, orexin neurons participate in the regulation of sympathetic activity, including effects on blood pressure and thermoregulation. Orexin is also essential in physiological responses to stress. Orexin-mediated processes may operate at two levels: 1) in sleep-wake and circadian states; and 2) in stress, e.g., the defense or “fight or flight” response and panic anxiety syndrome.

Respiratory manifestations of panic disorder in animals and humans: A unique opportunity to understand how supramedullary structures regulate breathing

“…Furthermore, ORX neurons were recently shown to exhibit CO 2 /H + sensing properties. When exposed to a hypercarbic environment, these cells appear to contribute to the hyperventilatory response (Nattie and Li, 2012;Williams et al, 2007). Orexinergic neurons also play an important role in the regulation of sleep and wakefulness and not surprisingly, the activity of these neurons is substantially attenuated by anesthesia, a property that must be considered when selecting an animal model (Kushikata et al, 2003;Zecharia et al, 2009).…”

“…In addition "classic" brainstem chemoreceptor (e.g. the retrotrapezoid nucleus; Guyenet, 2008), CO 2 concomitantly activates more rostral groups of neurons also endowed with specialized CO 2 sensing properties, including the basolateral amygdala (BLA) (Ziemann et al, 2009) and orexin (ORX) producing neurons of the dorso-medial/perifornical hypothalamus (DMH/PeF) (Gestreau et al, 2008;Nakamura et al, 2007;Nattie and Li, 2012;Williams et al, 2007) that regulate emotional reactions and "fight or flight" responses respectively ( Fig. 1) (Nakamura et al, 2009;Yoshida et al, 2006).…”

Orexins and fear: implications for the treatment of anxiety disorders

“…Changes in CO 2 and acid concentration may trigger panic attacks after a challenge test by increasing autonomic symptoms and promoting behavioral arousal [64]. Notably, recent evidence demonstrated that orexin neurons are highly sensitive to local changes in CO 2 /H + [65]. In a human study, orexin A plasma levels were dramatically increased in patients with chronic obstructive pulmonary disease (COPD), a condition associated with hypercapnia and a tenfold increased risk of panic attacks [66].…”

Clinical consequences of altered chemoreflex control

“…Secondary modulators also affect ventilation: voluntary control from the cerebral cortex through the corticospinal and corticobulbar tracts, the limbic system and hypothalamus can affect breathing (Evans, 2010; Evans et al, 1999; Kc and Dick, 2010; Nattie and Li, 2012; Shea, 1996). Receptors in the lung include stretch, irritant and J receptors and bronchial C-fibers (Kubin et al, 2006).…”