Medial vestibular connections with the hypocretin (orexin) system

Abstract

The mammalian medial vestibular nucleus (MVe) receives input from all vestibular endorgans and provides extensive projections to the central nervous system. Recent studies have demonstrated projections from the MVe to the circadian rhythm system. In addition, there are known projections from the MVe to regions considered to be involved in sleep and arousal. In this study, afferent and efferent subcortical connectivity of the medial vestibular nucleus of the golden hamster (Mesocricetus auratus) was evaluated using cholera toxin subunit-B (retrograde), Phaseolus vulgaris leucoagglutinin (anterograde), and pseudorabies virus (transneuronal retrograde) tract-tracing techniques. The results demonstrate MVe connections with regions mediating visuomotor and postural control, as previously observed in other mammals. The data also identify extensive projections from the MVe to regions mediating arousal and sleep-related functions, most of which receive immunohistochemically identified projections from the lateral hypothalamic hypocretin (orexin) neurons. These include the locus coeruleus, dorsal and pedunculopontine tegmental nuclei, dorsal raphe, and lateral preoptic area. The MVe itself receives a projection from hypocretin cells. CTB tracing demonstrated reciprocal connections between the MVe and most brain areas receiving MVe efferents. Virus tracing confirmed and extended the MVe afferent connections identified with CTB and additionally demonstrated transneuronal connectivity with the suprachiasmatic nucleus and the medial habenular nucleus. These anatomical data indicate that the vestibular system has access to a broad array of neural functions not typically associated with visuomotor, balance, or equilibrium, and that the MVe is likely to receive information from many of the same regions to which it projects.

The Moving History of Vestibular Stimulation as a Therapeutic Intervention

“…Some studies found prolonged quiet sleep during vestibular stimulation (Barnard and Bee, 1983;Johnston et al, 1997;Korner et al, 1990), while other studies found that it promoted wakefulness (Campos, 1994;Gregg et al, 1976), which is also in line with literature suggesting an influence of vestibular cues on arousal and sleep regulation (e.g. Horowitz et al, 2005). The velocity of rocking has been suggested to be crucial (Johnston et al, 1997): slower speed is thought to promote sleep (Gregg et al, 1976) while faster speed or a fall is thought to promote wake states (Campos, 1994) or even wake an organism from sleep (Horner et al, 1997).…”

“…The velocity of rocking has been suggested to be crucial (Johnston et al, 1997): slower speed is thought to promote sleep (Gregg et al, 1976) while faster speed or a fall is thought to promote wake states (Campos, 1994) or even wake an organism from sleep (Horner et al, 1997). On a neurophysiological level, an animal model showed that the medial vestibular nucleus projects onto hypocretin neurons and thus regulates sleep and arousal (Horowitz et al, 2005).…”

“…Moreover, it has been hypothesized that the vestibular system and emotional circuits overlap (Preuss et al, 2014a) or that CVS would target the inferior frontal gyrus, a region involved in unrealistic optimism (McKay et al, 2013). On an lower level, the medial vestibular nucleus located in the medulla oblongata is connected to different brain areas associated with nociception, sleep and arousal, homeostasis and eye movements (Horowitz et al, 2005). It remains to be seen how those structural connections translate to a more functional level.…”

The Moving History of Vestibular Stimulation as a Therapeutic Intervention

“…For example GVS increases GABA release in rats (Samoudi et al, 2012). But also the sleep-wake system is influenced by vestibular input as projections of the medial vestibular nucleus to hypocretin neurons and vice versa have been found (Horowitz et al, 2005).…”

“…Given the positive effect of arousal on memory retention (e.g. Sharot and Phelps, 2004), one could speculate that such results might be explained by arousal caused by vestibular stimulation (Horowitz et al, 2005, see also chapter 2.1). To further investigate this interesting question on the influence of vestibular-induced arousal, one could use different strengths of vestibular stimulation to see whether the positive effect on memory depends on stimulation parameters.…”