ORIGINAL ARTICLE
Vertigo and motion sickness. Part I:
Vestibular anatomy and physiology
Timothy P. Zajonc, MD; Peter S. Roland, MD
Abstract
Control of the symptoms of vertigo and motion sickness
requires consideration of the neurophysiology of areas
both intrinsic and extrinsic to the vestibular system propel:
We review the essential anatomy and physiology of the
vestibular system and the associated vomiting reflex.
Introduction
Vertigo is often accompanied by visceral autonomic symp-
toms, including pallor, diaphoresis, nausea , and vomiting.
Vertigo is similar to motion sickness in that both can be
caused by vestibular stimulation that does not match an
internal model of expected environmental stimuli. Indeed ,
a functioning vestibular system is necessary for the per-
ception of motion sickness.' For this reason, many of the
same drugs are used to treat both conditions. Selection of
a particular type of drug therapy can be facilitated by an
understanding of the essential anatomy and physiology of
the vestibular system and the associated vomiting reflex.
Vestibular pathways
The receptor cells for vestibular stimuli are the hair cells of
the vestibular labyrinth. Type I hair cells are flask-shaped
and connected to a single large afferent nerve fiber. Type
II cells are cylindrical, and they are innervated by a series
of bouton -type nerve endings at their base. These sensory
cells are found in the cristae at the ampullated ends of the
semicircular canals and in the maculae of the utricle and
sacculus. Movement of the endolymph in the semicircular
canals, and movement of the otoliths in the case of the
maculae, is translated by the hair cells into an electrical
impulse. This impulse is propagated by the afferent nerves
toward the vestibular nuclei. There are four vestibular nu-
clei: the superior vestibular nucleus, the lateral vestibular
nucleus , the medial vestibular nucleus, and the descending
From ENT Associates, John son City, Tenn . (Dr. Zajonc) , and the Depart-
ment of Otola ryngology-Head and Neck Surgery, Uni versity of
Texas Southwestern Medical Center at Dallas (Dr. Roland) .
Reprint requests: Peter S. Roland, MD , Professor and Chairm an, De-
partment of Otolaryngology-Head and Neck Surgery, University
of Texas Southwestern Medic al Center, 5323 Harry Hines Blvd.,
Dallas, TX 75390-9035. Phone : (2 14) 648-3102; fax: (214) 648-
2246 ; e-mail : peter.roland @utsouthwestern.edu
Volume 84, Number 9
vestibular nucleus. Secondary vestibular afferent fibers are
responsible for making connections with the contralateral
vestibular nuclei, oculomotor control areas, the cerebellum,
and the spinal cord.
The chief neurotransmitter in the vestibular nuclei is
believed to be the excitatory amino acid glutamate. Elec-
tron-microscope autoradiography demonstrates glutamate
uptake sites in the lateral and inferior vestibular nuclei of
cats .The number of these sites is significantly decreased by
previous sectioning of the vestibular nerve, indicating that
glutamate is involved in the transfer of signals from ves-
tibular afferent neurons . 1.2 Glutamate actions are mediated
by excitatory amino acid receptors. The four main families
of excitatory amino acid receptors are a-amino-3-hydroxy- .
5-methyl-4-isoxazole propionic acid receptors (AMPA),
N-methyl-D-aspartate receptors (NMDA), metabotropic
glutamate receptors, and kainic acid receptors. AMPA,
NMDA, and metabotropic receptors have been found in
the vestibular nuclei . 1.3 Glutamate appears to act primarily
on AMPA-type receptors in the vestibular nuclei.'
Acetylcholine has been identified in primary vestibular
afferents of the vestibul ar nuclei.' In cat studie s involving
measurements of the field potential of the lateral vestibular
nucleus, the application of acetylcholine produces the
same response as does stimulation of the vestibular nerve.
In addition, the response to stimulation of the vestibular
nerve is enhanced by inhibition of acetylcholinesterase
and blocked by the antimuscarinic drug scopolamine.l"
Muscarinic receptors are acetylcholine-binding receptors
that have historically been demonstrated to be activated
by muscarine and blocked by atropine.
Knowledge of muscarinic receptor subtypes and their
pharmacologic actions is increasing, and more effective
anticholinergic medications with fewer side effects are in
development. There are now five known structural subtypes
of muscarinic receptors, designated m, through ms' The
capitalized designations M" M 2, and M 3 represent phar-
macologic definitions, which are based on the actions of
various drugs that bind muscarinic receptors selectively. It
has been shown that the structural designations m, through
m3 cOlTelate with the pharmacologic definitions M, through
M 3, respectively. In situ hybridization studies of rat brain
have demonstrated a unique distribution of muscarinic
581
 ZAJONC, ROLAND

receptor subtypes. P The m l receptors are abundant in Neurokinin type I (NK I) receptors have been found in
the cerebral cortex, striatum, and hippocampus. The m z some vestibular afferents.' NK, receptors bind substance P,
recep tors are very rare in brain tissue; they are found in which is a neuroactive peptide. Substance P is thought to
significant quantities only in the media l septum and pons be involved in many actions throug hout the body, includ-
and in lesser amoun ts in the thalamus.The distribution of m3 ing the transmission of painful stimuli, but its role in the
recep tors is simi lar to that of m, receptors, but m3receptors vestibular system is unclear at this time ."
are also found in severa l thalamic nuclei and brainstem Other receptors found in the vestibular nuclei include D,
nuclei. The m4 receptors are found in the cortex , striatum , dopaminergic receptors, 5-HT IAand 5-HT2 (seroto ninergic)
and hippocampus, and the ms receptors are fou nd in very receptors, and (J,z - and PI-adrenergic receptors (table). 4.13.14
low levels in the hippocampus and some brains tem nuclei. Norepinephrine, which binds adrenergic receptors, has
Bovine brain studies have also revea led that muscar inic been reported to block neuronal firing in the medial ves-
receptors are found in the vestibular nuclei." Localization tibular nucleus while it stimulates neurons in the lateral
of receptor subtypes to specific areas of the brain allows vestibular nucleus.' :"
for the possibility of designi ng drugs that have a more
specific action. The cerebellu m
Another regulatory substance in the vestibular nuclei The cerebe llum is believed to functio n as a regu lator of
is histamine. H I' Hz, and H3 recep tors are present in the movement and posture by comparing movement intention
medial vestibular nucleus.t'? Field-potential recordings with movement performance and regulating the actions
demonstra te that the HI antagonist diphenhydramine of descending motor neurons . Information gathered on
decreases firing of polysynaptic pathways in the lateral movement intention is called internal feedback. Sensory
vestibular nucleus.':" information about motor performance is called external
Other inhibitory actions in the vestibular nuclei are me- feedback. Vestibular stim uli, represen ting spatial orienta -
diated by y-aminobutyric acid (GABA). Two subclasses tion, are also regarded as externa lfeedback. The cerebellum
of GABA rece ptors- GABA A and GABA B-are found compares internal and external feedback signals in order
in the vestibular nuclei . GABA A recep tors are bound by to regulate performance. The cerebellum is also believed
benzodiazepines for agonist effec ts. GABA B receptors to contain a conceptual internal model that reflects norma l
bind baclofen for agonist effects. Neuro ns from the con- sensory congruities for a given movement or posture.
tralateral vesti bular nuclei and Purki nje fibers from the When the comparison of the internal and external feedback
cerebellum are believed to exert their inhibitory effects signals does not fall within the parameters of this internal
via this GA BAergic system.' model, a sensory mismatch is said to exist. These sensory

Table. Anatomic distribution of receptors" :"

Area Vestibular
Receptor postrema PCRFINTS Cerebellum nuclei Cortex

AMPA/ NMDA + + + + +
Muscarinic + + + + +
Histaminic H2 H3 H1 H lI H2 , H3 H lI H2 , H3

GABAergic GABAA GABA A GABAA, GABAA, GABAA,

GABAB GABAB GABAB

Dopaminergic D2 , D3 D2 , D3 , D4 D3 D2 DlI D2 , D4 1 o,

Serotoninergic 5-HT3 5-HT1AJ 5-HT3 5-HT2 5-HT1A,5-HT2 5-HT2,5-HT3

a· Adrenergic + + a2 a2 a2

~ - A d rene r gic + + ~1I ~2 ~1 ~1I ~ 2

Key: p eRF = par vicellular reticular forma tion; NTS = nucleus tractus solitarius; AMPA = a-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid; NMDA = N-methyl -D-aspartate; GABA = y-aminobutyric acid.

582 ENT-Ear, Nose & Throat Journal s September 2005

 VERTIGO AN D MOTIO N SICKN ESS. PART I: VESTIBULAR ANATOM Y AN D PHYSIO LO GY

mismatches can develop as a

Organizational model of the vomiting pathway
result of new environmental
stimuli or erroneou s input
caused by disease . Upon the
detection of a mismatch , un-
comfortable sensations such
as disequi librium, vertigo, or
motion sickness occur. The
cerebellum is thought to pro-
mote short-term regulat ion Cortex and limbic system
and long-term habituation (poss ible sec ondary compa rator)
to compensate for these mis-
matched signals."
The idea that the cerebel- Inferior olive
lum functions as a regulator (voluntary motor-
co ntrol information)
of the vestibular system is
supported by the observation
that lesions of the cerebellar
flocculus inhibit adjustmen ts
to the gain of the vestibulo-
ocular reflex.l-'?Also, when
nodulectomy was performed
on cats, previo usly acquired Vomiting center
habituation to caloric stimu- (p eRF and NTS)

lation was lost. This lesion

Figure. Diagram represents the organization of the key areas and path ways f or the production of
also severe ly in terfered
emesis secondary to motion sickness and vertigo. (Cl'Z = chemo receptor trigger zone; PCRF =
with the cats' further ac- parvicellular reticular f ormation; NTS = nucleus tractus solitarius.)
quisition and retention of
habituation." Additionally,
dogs have been rendered immune to motion sickness by nuclei. There are many other cortica l and subcortical af-
ablatio n of the nodulus and uvula of the cerebellum.P'" ferent connections to the PCRF, but the exact means by
Neurons projec ting from the inferior olivary nucleus to the which these pathways are integrated and this information
cerebellar nuclei and cerebellar cortex are also necessary is used to initiate vomiting are not clear. I
for vestibular compensation. The inferior olivary neurons The nucleus tractus solitarius is closely related to the
are believed to carry information about voluntary motor PCRF. It serves as a major coordina ting center for auto-
movements. Destructionof the inferior olive in rats prevents nomic functions in the brainstem and undou btedly plays
compensation after unilateral labyrinthectomy. I.21 a significan t role in the vomiting reflex. It receives vagal,
vestib ular, area postrema , and limbic inputs.' The nucleus
Vomiting center tractu s solitarius is rich in catecholamine-containing
The area of the brainstem known as the parvicellu lar fibers, has dense GABA input , and also contains 5-HT 'A
reticularform ation (PCRF) is believed to function as the receptor s.
vomiting center, where the vomiting reflex is initiated and
coordinated. Electrical stimulation of this area in cats has Area postrema
been shown to evoke vomiting.':" The PCRF is located The area postrema is located laterally along the floor of
ventral to the vestibular nucle i and medial to, as well as the fourth ventricle; it is not protected by the blood-brain
partially coextensive with, the elongated nucleus of the barrier. Early studie s in dogs showed that ablation of this
spinal tract of the trigeminal nerve.The PCRFprojects fibers area prevented motion sickne ss. Later studies in both cats
to the motor nucleus of the facial nerve, to the'hypoglos- and squirrel monkey s, which might have involved more
sal nucleus, and to the parabrachial nuclei, which contai n accurate ablation of the area postrema, demonstra ted no
some respiratory centers . I The se connections may allow protection from motion-induced emesis. I The facts that
for coordination of the vomiting reflex. Also, the PCRF is stimulation of the area postrema produces vomiting in
traversed by an extensive system of commiss ural fibers that cats and that it is not protected by the blood-brain barrier
interconnect the vestibular nuclear comp lexes. It has been suggest that the area postrema contains the chemorece ptor
sugges ted that fine axon collaterals may arise from these trigger zone for the production of vomiting in response to
comm issural fibers to connect the PCRF to the vestibular noxious chemicals.

Volume 84, Number 9 583

 ZAlONe, ROLAND
Organizational model
The currently understood model for the production of
vertigo or motion sickness includes a system in which
information is gath ered from vestibular, visua l, proprio-
ceptive, and cortical activity (figure). This information is
then compared with an internal model of expected input
congruity. Detection of a stimulus mism atch promotes the
symptoms associated with vertigo and motion sickness.
Thi s comparator also serves to promote habit uation to new
environmental stimuli or compensation for erroneous input
caused by disease.
It is interesting that some medications that are excellent
antiemetics do not prevent vertigo or motion sickness.
One such medication, ondansetron, is often used for the
prevention of chemotherapy-induced nau sea . It acts on
5-HT3 receptors in the area postrema. Activity in this
location would not necessarily prevent stimul ation of the
vestibular nuclei from ultimatelycausing nausea and vomit-
ing. However, patients who are particularly susceptible to
motion sickness also demonstrate increased responses to
other vomiting center stimuli.This may provide a rat ionale
for the use of general antiemetics in vertigo associated
with nausea.v-"
The role of medications in treating ver tigo and mot ion
sickness will be reviewed in part II of this article in an
upcoming issue.
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