Increased and decreased muscle tone with orexin (hypocretin) microinjections in the locus coeruleus and pontine inhibitory area

Orexin-A (OX-A) and orexin-B (OX-B) (hypocretin 1 and hypocretin 2) are syn thesized in neurons of the perifornical, dorsomedial, lateral, and posterio r hypothalamus. The locus coeruleus (LC) receives the densest extrahypothal amic projections of the orexin (OX) system. Recent evidence suggests that d escending projections of the LC have a facilitatory role in the regulation of muscle tone. The pontine inhibitory area (PIA), located ventral to LC, r eceives a moderate OX projection and participates in the suppression of mus cle tone in rapid-eye-movement sleep. We have examined the role of OX-A and -B in muscle-tone control using microinjections (0.1 muM to 1 mM, 0.2 mul) into the LC and PIA in decerebrate rats. OX-A and -B microinjections into the LC produced ipsi- or bilateral hindlimb muscle-tone facilitation. The a ctivity of LC units was correlated with the extent of hindlimb muscle-tone facilitation after OX microinjections (100 muM, 1 mul) into fourth ventricl e. Microinjections of OX-A and -B into the PIA produced muscle-tone inhibit ion. We did not observe any significant difference in the effect of OX-A an d -B on muscle tone at either site. Our data suggest that OX release activa tes LC units and increases noradrenergic tonus in the CNS. Moreover, OX-A a nd -B may also regulate the activity of pontine cholinoceptive and choliner gic neurons participating in muscle-tone suppression. Loss of OX function m ay therefore disturb both facilitatory and inhibitory motor processes.