Orexin-A inputs onto visuomotor cell groups in the monkey brainstem.

Orexin-A, synthesized by neurons of the lateral hypothalamus helps to maintain wakefulness through excitatory projections to nuclei involved in arousal. Obvious changes in eye movements, eyelid position and pupil reactions seen in the transition to sleep led to the investigation of orexin-A projections to visuomotor cell groups to determine whether direct pathways exist that may modify visuomotor behaviors during the sleep-wake cycle. Histological markers were used to define these specific visuomotor cell groups in monkey brainstem sections and combined with orexin-A immunostaining. The dense supply by orexin-A boutons around adjacent neurons in the dorsal raphe nucleus served as a control standard for a strong orexin-A input. The quantitative analysis assessing various functional cell groups of the oculomotor system revealed that almost no input from orexin-A terminals reached motoneurons supplying the singly-innervated muscle fibers of the extraocular muscles in the oculomotor nucleus, the omnipause neurons in the nucleus raphe interpositus and the premotor neurons in the rostral interstitial nucleus of the medial longitudinal fasciculus. In contrast, the motoneurons supplying the multiply-innervated muscle fibers of the extraocular muscles, the motoneurons of the levator palpebrae muscle in the central caudal nucleus, and especially the preganglionic neurons supplying the ciliary ganglion received a strong orexin input. We interpret these results as evidence that orexin-A does modulate pupil size, lid position, and possibly convergence and eye alignment via the motoneurons of multiply-innervated muscle fibres. However orexin-A does not directly modulate premotor pathways for saccades or the singly-innervated muscle fibre motoneurons.