Effects of visceral inputs on the processing of labyrinthine signals by the inferior and caudal medial vestibular nuclei: ramifications for the production of motion sickness

Abstract

Neurons located in the caudal aspect of the vestibular nucleus complex have been shown to receive visceral inputs, and project to brainstem regions that participate in generating emesis, such as nucleus tractus solitarius and the “vomiting region” in the lateral tegmental field (LTF). Consequently, it has been hypothesized that neurons in the caudal vestibular nuclei participate in triggering motion sickness, and that visceral inputs to the vestibular nucleus complex can affect motion sickness susceptibility. To obtain supporting evidence for this hypothesis, we determined the effects of intragastric infusion of copper sulfate (CuSO4) on responses of neurons in the inferior and caudal medial vestibular nuclei to rotations in vertical planes. CuSO4 readily elicits nausea and emesis by activating gastrointestinal afferents. Infusion of CuSO4 produced a >30% change in spontaneous firing rate of approximately one-third of neurons in the caudal aspect of the vestibular nucleus complex. These changes in firing rate developed over several minutes, presumably in tandem with the emetic response. The gains of responses to vertical vestibular stimulation of a larger fraction (approximately two-thirds) of caudal vestibular nucleus neurons were altered over 30% by administration of copper sulfate. The response gains of some units went up, and others went down, and there was no significant relationship with concurrent spontaneous firing rate change. These findings support the notion that the effects of visceral inputs on motion sickness susceptibility are mediated in part through the caudal vestibular nuclei. However, our previous studies showed that infusion of CuSO4 produced larger changes in responses to vestibular stimulation of LTF neurons, as well as parabrachial nucleus neurons that are believed to participate in generating nausea. Thus, integrative effects of gastrointestinal inputs on the processing of labyrinthine inputs must occur at brain sites that participate in eliciting motion sickness in addition to the caudal vestibular nuclei. It seems likely that the occurrence of motion sickness requires converging inputs to brain areas that generate nausea and vomiting from a variety of regions that process vestibular signals.

Integration of vestibular and gastrointestinal inputs by cerebellar fastigial nucleus neurons: multisensory influences on motion sickness

“…In particular, intragastric injection of CuSO 4 resulted in a >50% alteration in the magnitude of responses to vestibular stimulation of 28/51 (55%) parabrachial nucleus neurons (Suzuki et al 2012), 8/22 (36%) lateral tegmental field neurons (Moy et al 2012), and 16/49 (33%) neurons in the caudal aspect of the vestibular nucleus complex (Arshian et al 2013), but less than 10% fastigial nucleus neurons (p < 0.0001, χ 2 test). Furthermore, the spatial and temporal properties of responses to vestibular stimulation of the vast majority of fastigial nucleus neurons were unaffected after CuSO 4 was placed in the stomach.…”

“…Similarly, another study indicated that the responses to vestibular stimulation of neurons in the rostral ventrolateral medulla that participate in cardiovascular regulation are exaggerated in decerebrate cats (Destefino et al 2011). Other studies compared responses to whole-body rotations of neurons in the caudal vestibular nuclei in decerebrate (Endo et al 1995; Arshian et al 2013) and conscious felines (Miller et al 2008a; McCall et al 2013) and reported little difference in findings between the preparations. Hence, it appears that decerebration is more likely to unmask responses to vestibular stimulation in brain regions that receive multisynaptic inputs from the labyrinth than areas that receive inputs directly from the inner ear.…”

“…The University of Pittsburgh’s Institutional Animal Care and Use Committee (IACUC) prospectively approved all procedures on animals, which were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, National Academies Press, Washington D.C., 2011). The experimental protocol used in these experiments has been validated and thoroughly described in previous manuscripts (Sugiyama et al 2011; Moy et al 2012; Suzuki et al 2012; Arshian et al 2013), and thus will only be briefly described below.…”

“…In a series of experiments, we have investigated the effects of intragastric injection of the emetic compound copper sulfate (CuSO 4 ) on the processing of vestibular signals by brainstem regions that mediate nausea and vomiting (Sugiyama et al 2011; Moy et al 2012; Suzuki et al 2012; Arshian et al 2013). The responses to whole-body rotations that activate labyrinthine receptors of neurons in some of these areas, particularly the parabrachial nucleus (Suzuki et al 2012) and the lateral tegmental field (Moy et al 2012), were profoundly altered when CuSO 4 was present in the stomach.…”

“…As in our previous studies that considered the effects of CuSO 4 administration on the processing of labyrinthine inputs (Sugiyama et al 2011; Moy et al 2012; Suzuki et al 2012; Arshian et al 2013), recordings were conducted in decerebrate cats. We focused the recordings on the rostral portion of the fastigial nucleus, which plays a primary role in spatial orientation (Buttner et al 1991; Thach et al 1992; Siebold et al 1997; Mori et al 1998; Mori et al 2004), in contrast to the caudal aspect of the fastigial nucleus whose physiological role is related to the control of eye movements (Gardner and Fuchs 1975; Buttner et al 1991; Robinson and Fuchs 2001; Brettler and Fuchs 2002; Shaikh et al 2005).…”