View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector REVIEW published: 27 March 2017 doi: 10.3389/fneur.2017.00112 Descending influences on Vestibulospinal and Vestibulosympathetic Reflexes Andrew A. McCall, Derek M. Miller and Bill J. Yates* Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA This review considers the integration of vestibular and other signals by the central ner- vous system pathways that participate in balance control and blood pressure regulation, with an emphasis on how this integration may modify posture-related responses in accordance with behavioral context. Two pathways convey vestibular signals to limb motoneurons: the lateral vestibulospinal tract and reticulospinal projections. Both path- ways receive direct inputs from the cerebral cortex and cerebellum, and also integrate vestibular, spinal, and other inputs. Decerebration in animals or strokes that interrupt corticobulbar projections in humans alter the gain of vestibulospinal reflexes and the responses of vestibular nucleus neurons to particular stimuli. This evidence shows that supratentorial regions modify the activity of the vestibular system, but the functional importance of descending influences on vestibulospinal reflexes acting on the limbs Edited by: is currently unknown. It is often overlooked that the vestibulospinal and reticulospinal Bernard Cohen, Icahn School of Medicine at systems mainly terminate on spinal interneurons, and not directly on motoneurons, yet Mount Sinai, USA little is known about the transformation of vestibular signals that occurs in the spinal Reviewed by: cord. Unexpected changes in body position that elicit vestibulospinal reflexes can also William Michael King, produce vestibulosympathetic responses that serve to maintain stable blood pressure. University of Michigan, USA Richard Nichols, Vestibulosympathetic reflexes are mediated, at least in part, through a specialized group Georgia Institute of Technology, USA of reticulospinal neurons in the rostral ventrolateral medulla that project to sympathetic *Correspondence: preganglionic neurons in the spinal cord. However, other pathways may also contribute Bill J. Yates to these responses, including those that dually participate in motor control and reg- [email protected] ulation of sympathetic nervous system activity. Vestibulosympathetic reflexes differ in Specialty section: conscious and decerebrate animals, indicating that supratentorial regions alter these This article was submitted to responses. However, as with vestibular reflexes acting on the limbs, little is known about Neuro-otology, a section of the journal the physiological significance of descending control of vestibulosympathetic pathways. Frontiers in Neurology Keywords: vestibular nuclei, reticular formation, posture, balance, vestibulo-autonomic interactions, sympathetic Received: 16 January 2017 nervous system Accepted: 09 March 2017 Published: 27 March 2017 Citation: McCall AA, Miller DM and Yates BJ INTRODUCTION (2017) Descending Influences on Vestibulospinal and Historically, vestibular-elicited reflexes were considered to be stereotyped responses to particular Vestibulosympathetic Reflexes. head movements (1–3). However, recent research has shown that vestibular nucleus neurons Front. Neurol. 8:112. receive inputs from a variety of sources in addition to the inner ear, such that vestibular-elicited doi: 10.3389/fneur.2017.00112 reflexes are shaped in accordance with ongoing movements and behaviors. For example, the work of Frontiers in Neurology | www.frontiersin.org 1 March 2017 | Volume 8 | Article 112 McCall et al. Descending Modulation of Vestibular Function Cullen et al. showed that some vestibular nucleus neurons com- connections of LVST axons with limb α-motoneurons are poly- pare the planned head movement with feedback sensory signals, synaptic, although some weak monosynaptic inputs may occur and discharge in accordance with deviations from the intended to hindlimb motoneurons (17, 18). These observations suggest movement (4–6). However, most studies that considered the that signals conveyed through the LVST are processed and likely modification of vestibular responses in a behavioral context modified by spinal interneurons prior to reaching motoneurons. focused on the control of eye movements and gaze (4, 7, 8), but The LVST mainly has excitatory effects on extensor motoneu- not vestibular reflexes acting on the limbs and vestibulosympa- rons, with some inhibitory effects on flexor motoneurons (17, thetic responses that regulate blood pressure. 18). At least in cats, approximately half of LVST axons that This review considers the integration of vestibular and other terminate in lower cervical and upper thoracic spinal segments signals by the central nervous system pathways that participate in (which contain forelimb motoneurons) also have a branch to the balance control and blood pressure regulation, with an emphasis lumbar spinal cord, raising the prospect that some LVST neurons on how this integration may modify posture-related responses in simultaneously control muscle activity in both the forelimbs and accordance with behavioral context. It starts with an overview of hindlimbs (19). the pathways that relay vestibular signals to limb motoneurons Neurons whose axons project to the spinal cord in the and sympathetic preganglionic neurons, and then considers pontine and medullary reticulospinal tracts (RST) also receive the integration of signals that occurs in these pathways. Next, extensive vestibular inputs (20–23). These vestibular inputs are evidence is presented that descending signals modify vestibulo- polysynaptic, indicating that vestibular nucleus neurons and spinal reflexes acting on the limbs as well as vestibulosympathetic other pathways convey labyrinthine signals to RST neurons, but reflexes, presumably to shape the responses in accordance with that RST neurons do not receive direct inputs from vestibular physiological challenges that are present or anticipated, as well nerve fibers (20, 21). RST neurons have both excitatory and as behaviors and movements that are planned or being imple- inhibitory effects on flexor and extensor forelimb and hindlimb mented. Finally, directions for future research are discussed. In motoneurons (24–28), as opposed to LVST neurons that tend total, the review describes how perspectives on vestibulospinal to excite extensor motoneurons and inhibit flexor motoneurons and vestibulosympathetic responses have evolved, such that these (17, 18). However, LVST and RST (24, 25, 29) neurons are similar responses are now considered to be components of a hierarchy of in that their effects on the excitability of limb motoneurons are systems that are activated to achieve stable movements without mainly polysynaptic, via spinal interneurons, and that the axons disturbances in blood pressure. of both RST (30) and LVST (19) neurons are highly branched. Thus, the two major pathways that convey vestibular signals to ORGANIZATION OF VESTIBULOSPINAL limb motoneurons have some similarities, as well as some major AND VESTIBULOSYMPATHETIC differences. PATHWAYS Vestibulosympathetic Pathways The first key study demonstrating that the vestibular system Vestibulospinal Pathways Acting on the contributes to cardiovascular regulation was published by Doba Limbs and Reis (31). As discussed in detail in a recent review (32), Two pathways originating in the vestibular nuclei provide inputs considerable evidence from experiments in both human and to spinal cord segments containing limb motoneurons. The animal subjects has shown that the vestibular system participates medial vestibulospinal tract (MVST) originates in the rostral por- in regulating sympathetic nervous system activity, to provide for tion of the descending vestibular nucleus as well as the bordering adjustments in blood pressure during movement. areas of the medial and lateral vestibular nuclei (9–11). The main A column of reticulospinal neurons located near the ventral influences of this pathway are on upper-body musculature, par- surface of the rostral medulla plays a predominant role in control- ticularly neck musculature, although a small fraction of MVST ling sympathetic nerve activity and blood pressure (33–36). These projections provide inputs to segments containing forelimb neurons comprise the rostral ventrolateral medulla (RVLM). motoneurons (10–12). The lateral vestibulospinal tract (LVST) Lesions of the RVLM abolished vestibulosympathetic responses originates mainly from the lateral vestibular nucleus, with some (37), suggesting that reticulospinal neurons with cell bodies in the contribution from the descending nucleus (9–11). This tract RVLM constitute the major pathway through which vestibular extends the entire length of the spinal cord and provides exten- signals are conveyed to sympathetic preganglionic neurons in sive inputs to spinal cord segments containing motoneurons that the thoracic spinal cord. RVLM neurons are components of the innervate forelimb and hindlimb muscles (13, 14). Since the LVST baroreceptor reflex arc, which also includes neurons in nucleus provides much more extensive inputs to the spinal cord segments tractus solitarius (NTS) that receive baroreceptor inputs, as containing limb motoneurons than does the MVST (10–12), it well as inhibitory neurons in the caudal ventrolateral medulla likely plays a predominant role in controlling postural responses