Introduction

Remember the dizzy feeling you got as a child after you jumped off the merry-go-round or spun around like a top? These feelings result from activation of the vestibular system, which detects our movements through space but is not a conscious sense like vision or hearing. In fact, most vestibular functions are imperceptible, but vestibular-related sensations such as motion sickness can pop up rapidly when riding on a roller coaster, having a bumpy plane ride, or a sailing a boat in rough seas. However, these sensations are really side effects and the vestibular system is actually extremely important for everyday activities, with vestibular signals being involved in much of the brain’s information processing that controls such fundamental functions as balance, posture, gaze stabilization, spatial orientation, and navigation, to name a few. In many regions of the brain, vestibular information is combined with signals from the other senses as well as with motor information to give rise to motion perception, body awareness, and behavioral control. Here, we will explore the workings of the vestibular system and consider some of the integrated computations the brain performs using vestibular signals to guide our common behavior.

Structure of the vestibular receptors

The vestibular receptors lie in the inner ear next to the auditory cochlea. They detect rotational motion (head turns), linear motion (translations), and tilts of the head relative to gravity and transduce these motions into neural signals that can be sent to the brain. There are five vestibular receptors in each ear (Hearing module, Figure 1- http://noba.to/jry3cu78), including three semicircular canals (horizontal, anterior, and posterior) that transduce rotational angular accelerations and two otolith receptors (utricle and saccule) that transduce linear accelerations (Lindeman, 1969). Together, the semicircular canals and otolith organs can respond to head motion and maintained static head position relative to gravity in all directions in 3D space.

These receptors are contained in a series of interconnected fluid filled tubes that are protected by a dense, overlying bone (Iurato, 1967). Each of the three semicircular canals lies in a plane that is orthogonal to the other two. The horizontal semicircular canal lies in a roughly horizontal head plane, whereas the anterior and posterior semicircular canals lie vertically in the head (Blanks, Curthoys, Bennett, & Markham, 1985). The semicircular canal receptor cells, termed hair cells, are located only in the middle of the circular tubes in a special epithelium, covered by a gelatinous membrane that stretches across the tube to form a fluid-tight seal like the skin of a drum (Figures 1A and 1B). Hair cells are so named due to an array of nearly 100 staggered-height stereocilia (like a church pipe organ) that protrude from the top of the cell into the overlying gelatin membrane (Wersäll, 1956). The shortest stereocilia are at one end of the cell and the tallest at the other (Lindeman, 1969). When the head is rotated, the fluid in the semicircular canals lags behind the head motion and pushes on the gelatin membrane, which bends the stereocilia.

As shown in Figure 2, when the head moves toward the receptor hair cells (e.g., left head turns for the left horizontal semicircular canal), the stereocilia are bent toward the tallest end and special mechanically gated ion channels in the tips of the cilia open, which excites (depolarizes) the cell (Shotwell, Jacobs, & Hudspeth, 1981). Head motion in the opposite direction causes bending toward the smallest stereocilia, which closes the channels and inhibits (hyperpolarizes) the cell. The left and right ear semicircular canals have opposite polarity, so for example, when you turn your head to the left, the receptors in the left horizontal semicircular canal will be excited while right ear horizontal canal receptors will be inhibited (Figure 3). The same relationship is true for the vertical semicircular canals. Vestibular afferent nerve fibers innervate the base of the hair cell and increase or decrease their neural firing rate as the receptor cell is excited or inhibited (Dickman and Correia, 1989), respectively, and then carry these signals regarding head rotational motion to the brain as part of the vestibulocochlear nerve (Cranial nerve VIII). They enter the brainstem and terminate in the ipsilateral vestibular nuclei, cerebellum, and reticular formation (Carleton & Carpenter, 1984; Dickman & Fang, 1996). The primary vestibular hair cell and afferent neurotransmitters are glutamate and aspartate. Due to the mechanical properties of the vestibular receptor system, rotational accelerations of the head are integrated into velocity signals (Van Egmond, Groen, & Jongkess, 1949) that are then encoded by semicircular canal afferents (Fernandez & Goldberg, 1971). Detection thresholds for rotational motion have shown that afferents can discriminate differences in head velocity on the order of 2 deg/sec, but also are sensitive to a broad range of natural head movements up to high head speeds in the hundreds of deg/sec (as you might experience when you make a fast head turn toward a loud sound, or are performing gymnastics; Sadeghi, Chacron, Taylor, & Cullen, 2007; Yu, Dickman, & Angelaki, 2012).

Otolith receptors are sensitive to linear accelerations and tilts of the head relative to gravity (Fernandez & Goldberg, 1976a). The utricle otolith receptor lies parallel to the horizontal semicircular canal and the saccule receptor lies vertical in the head (Hearing module, Figure 1- http://noba.to/jry3cu78). As shown in Figure 4, a special otolith epithelium contains receptor hair cells whose stereocilia extend into a gelatin membrane that is covered by a layer of calcium carbonate crystals, termed otoconia, like rocks piled up to form a jetty (Lindeman, 1969). Otoconia are not affected by fluid movements but instead are displaced by linear accelerations, including translations (e.g., forward/backward or upward/downward motions) or changes in head position relative to gravity. These linear accelerations produce displacements of the otoconia (due to their high mass), much like rocks rolling down a hill or your coffee cup falling off the car dashboard when you push the gas pedal. Movements of the otoconia bend the hair cell stereocilia and open/close channels in a similar way to that described for the semicircular canals. However, otolith hair cells are polarized such that the tallest stereocilia are pointing toward the center of the utricle and away from the center in the saccule, which effectively splits the receptors into two opposing groups (Flock, 1964; Lindeman, 1969). In this way, some hair cells are excited and some inhibited for each linear motion force or head tilt experienced, with the population of receptors and their innervating afferents being directionally tuned to all motions or head tilts in 3D space (Fernandez & Goldberg, 1976b).

All vestibular hair cells and afferents receive connections from vestibular efferents, which are fibers projecting from the brain out to the vestibular receptor organs, whose function is not well understood. It is thought that efferents control the sensitivity of the receptor (Boyle, Carey, & Highstein, 1991). The primary efferents neurotransmitter is acetylcholine (Anniko & Arnold, 1991).

The vestibular nuclei

The vestibular nuclei comprise a large set of neural elements in the brainstem that receive motion and other multisensory signals, then regulate movement responses and sensory experience. Many vestibular nuclei neurons have reciprocal connections with the cerebellum that form important regulatory mechanisms for the control of eye movements, head movements, and posture. There are four major vestibular nuclei that lie in the rostral medulla and caudal pons of the brainstem; all receive direct input from vestibular afferents (Brodal, 1984; Precht & Shimazu, 1965). Many of these nuclei neurons receive convergent motion information from the opposite ear through an inhibitory commissural pathway that uses gamma-aminobutyric acid (GABA) as a neurotransmitter (Kasahara & Uchino, 1974; Shimazu & Precht, 1966). The commissural pathway is highly organized such that cells receiving horizontal excitatory canal signals from the ipsilateral ear will also receive contralateral inhibitory horizontal canal signals from the opposite ear This fact gives rise to a “push-pull” vestibular function, whereby directional sensitivity to head movement is coded by opposing receptor signals. Because vestibular nuclei neurons receive information from bilateral inner ear receptors and because they maintain a high spontaneous firing rate (nearly 100 impulses/sec), they are thought to act to “compare” the relative discharge rates of left vs. right canal afferent firing activity. For example, during a leftward head turn, left brainstem nuclei neurons receive high firing-rate information from the left horizontal canal and low firing-rate information from the right horizontal canal. The comparison of activity is interpreted as a left head turn. Similar nuclei neuron responses exist when the head is pitched or rolled, with the vertical semicircular canals being stimulated by the rotational motion in their sensitivity planes. However, the opposing push-pull response from the vertical canals occurs with the anterior semicircular canal in one ear and the co-planar posterior semicircular canal of the opposite ear. Damage or disease that interrupts inner ear signal information from one side of the head can change the normal resting activity in the VIIIth nerve afferent fibers and will be interpreted by the brain as a head rotation, even though the head is stationary. These effects often lead to illusions of spinning or rotating that can be quite upsetting and may produce nausea or vomiting. However, over time the commissural fibers provide for vestibular compensation, a process by which the loss of unilateral vestibular receptor function is partially restored centrally and behavioral responses, such as the vestibuloocular reflex (VOR) and postural responses, mostly recover (Beraneck et al., 2003; Fetter & Zee, 1988,; Newlands, Hesse, Haque, & Angelaki, 2001; Newlands & Perachio, 1990).

In addition to the commissural pathway, many vestibular nuclei neurons receive proprioceptive signals from the spinal cord regarding muscle movement and position, visual signals regarding spatial motion, other multisensory (e.g., trigeminal) signals, and higher order signals from the cortex. It is thought that the cortical inputs regulate fine gaze and postural control, as well as suppress the normal compensatory reflexes during motion in order to elicit volitional movements. Of special significance are convergent signals from the semicircular canal and otolith afferents that allow central vestibular neurons to compute specific properties of head motion (Dickman & Angelaki, 2002). For example, Einstein (1907) showed that linear accelerations are equivalent whether they arise from translational motion or from tilts of the head relative to gravity. The otolith receptors cannot discriminate between the two, so how is it that we can tell the difference between when we are translating forward and tilting backward, where the linear acceleration signaled by the otolith afferents is the same? Vestibular nuclei and cerebellar neurons use convergent signals from both the semicircular canals and the otolith receptors to discriminate between tilt and translation, and as a result, some cells encode head tilt (Zhou, 2006) while other cells encode translational motion (Angelaki, Shaikh, Green, & Dickman, 2004).

Vestibuloocular system

The vestibular system is responsible for controlling gaze stability during motion (Crane & Demer, 1997). For example, if we want to read the sign in a store window while walking by, we must maintain foveal fixation on the words while compensating for the combined rotational and translational head movements incurred during our stride. The vestibular system regulates compensatory eye, neck, spinal, and limb movements in order to maintain gaze (Keshner & Peterson, 1995). One of the major components contributing to gaze stability is the VOR, which produces reflexive eye movements that are equal in magnitude and opposite in direction to the perceived head motion in 3D space (Wilson et al., 1995). The VOR is so accurate and fast that it allows people to maintain visual fixation on objects of interest while experiencing demanding motion conditions, such as running, skiing, playing tennis, and driving. In fact, gaze stabilization in humans has been shown to be completely compensatory (essentially perfect) for most natural behaviors. To produce the VOR, vestibular neurons must control each of the six pairs of eye muscles in unison through a specific set of connections to the oculomotor nuclei (Ezure & Graf, 1984). The anterior and posterior semicircular canals along with the saccule control vertical and torsional (turning of the eye around the line of sight) eye movements, while the horizontal canals and the utricle control horizontal eye movements.

To understand how the VOR works, let’s take the example of the compensatory response for a leftward head turn while reading the words on a computer screen. The basic pathway consists of horizontal semicircular canal afferents that project to specific neurons in the vestibular nuclei. These nuclei cells, in turn, send an excitatory signal to the contralateral abducens nucleus, which projects through the sixth cranial nerve to innervate the lateral rectus muscle (Figure 5). Some abducens neurons send an excitatory projection back across the midline to a subdivision of cells in the ipsilateral oculomotor nucleus, which, in turn, projects through the third cranial nerve to innervate the right (ipsilateral) medial rectus muscle. When a leftward head turn is made, the left horizontal canal vestibular afferents will increase their firing rate and consequently increase the activity of vestibular nuclei neurons projecting to the opposite (contralateral) right abducens nucleus. The abducens neurons produce contraction of the right lateral rectus and, through a separate cell projection to the left oculomotor nucleus, excite the left medial rectus muscles. In addition, matching bilateral inhibitory connections relax the left lateral rectus and right medial rectus eye muscles. The resulting rightward eye movement for both eyes stabilizes the object of interest upon the retina for greatest visual acuity.

During linear translations, a different type of VOR also occurs (Paige & Tomko, 1991). For example, sideways motion to the left results in a horizontal rightward eye movement to maintain visual stability on an object of interest. In a similar manner, vertical up–down head movements (such as occur while walking or running) elicit oppositely directed vertical eye movements (Angelaki, McHenry, & Hess, 2000). For these reflexes, the amplitude of the translational VOR depends on viewing distance. This is due to the fact that the vergence angle (i.e., the angle between the lines of sight for each eye) varies as a function of the inverse of the distance to the viewed visual object (Schwarz, Busettini, & Miles, 1989). Visual objects that are far away (2 meters or more) require no vergence angle, but as the visual objects get closer (e.g., when holding your finger close to your nose), a large vergence angle is needed. During translational motion, the eyes will change their vergence angle as the visual object moves from close to farther away (or vice versa). These responses are a result of activation of the otolith receptors, with connections to the oculomotor nuclei similar to those described above for the rotational vestibuloocular reflex. With tilts of the head, the resulting eye movement is termed torsion, and consists of a rotational eye movement around the line of sight that is in the direction opposite to the head tilt. As mentioned above, there are major reciprocal connections between the vestibular nuclei and the cerebellum. It has been well established that these connections are crucial for adaptive motor learning in the vestibuloocular reflex (Lisberger, Pavelko, & Broussard, 1994).

Vestibulo-spinal network

There are two vestibular descending pathways that regulate body muscle responses to motion and gravity, consisting of the lateral vestibulo-spinal tract (LVST) and the medial vestibulo-spinal tract (MVST). Reflexive control of head and neck muscles arises through the neurons in the medial vestibulospinal tract (MVST). These neurons comprise the rapid vestibulocollic reflex (VCR) that serves to stabilize the head in space and participates in gaze control (Peterson, Goldber, Bilotto, & Fuller, 1985). The MVST neurons receive input from vestibular receptors and the cerebellum, and somatosensory information from the spinal cord. MVST neurons carry both excitatory and inhibitory signals to innervate neck flexor and extensor motor neurons in the spinal cord. For example, if one trips over a crack in the pavement while walking, MVST neurons will receive downward and forward linear acceleration signals from the otolith receptors and forward rotation acceleration signals from the vertical semicircular canals. The VCR will compensate by providing excitatory signals to the dorsal neck flexor muscles and inhibitory signals to the ventral neck extensor muscles, which moves the head upward and opposite to the falling motion to protect it from impact.

The LVST comprises a topographic organization of vestibular nuclei cells that receive substantial input from the cerebellum, proprioceptive inputs from the spinal cord, and convergent afferent signals from vestibular receptors. LVST fibers project ipsilateral to many levels of motor neurons in the cord to provide coordination of different muscle groups for postural control (Shinoda, Sugiuchi, Futami, Ando, & Kawasaki, 1994). LVST neurons contain either acetylcholine or glutamate as a neurotransmitter and exert an excitatory influence upon extensor muscle motor neurons. For example, LVST fibers produce extension of the contralateral axial and limb musculature when the body is tilted sideways. These actions serve to stabilize the body’s center of gravity in order to preserve upright posture.

Vestibulo-autonomic control

Some vestibular nucleus neurons send projections to the reticular formation, dorsal pontine nuclei, and nucleus of the solitary tract. These connections regulate breathing and circulation through compensatory vestibular autonomic responses that stabilize respiration and blood pressure during body motion and changes relative to gravity. They may also be important for induction of motion sickness and emesis.

Vestibular signals in the thalamus and cortex

The cognitive perception of motion, spatial orientation, and navigation through space arises through multisensory information from vestibular, visual, and somatosensory signals in the thalamus and cortex (Figure 6A). Vestibular nuclei neurons project bilaterally to the several thalamic regions. Neurons in the ventral posterior group respond to either vestibular signals alone, or to vestibular plus somatosensory signals, and projects to primary somatosensory cortex (area 3a, 2v), somatosensory association cortex, posterior parietal cortex (areas 5 and 7), and the insula of the temporal cortex (Marlinski & McCrea, 2008; Meng, May, Dickman, & Angelaki, 2007). The posterior nuclear group (PO), near the medial geniculate body, receives both vestibular and auditory signals as well as inputs from the superior colliculus and spinal cord, indicating an integration of multiple sensory signals. Some anterior pulvinar neurons also respond to motion stimuli and project to cortical area 3a, the posterior insula, and the temporo-parietal cortex (PIVC). In humans, electrical stimulation of the thalamic areas produces sensations of movement and sometimes dizziness.

Area 2v cells respond to motion, and electrical stimulation of this area in humans produces sensations of moving, spinning, or dizziness. Area 3a lies at the base of the central sulcus adjacent to the motor cortex and is thought to be involved in integrative motor control of the head and body (Guldin, Akbarian, & Grusser, 1992). Neurons in the PIVC are multisensory, responding to body motion, somatosensory, proprioceptive, and visual motion stimuli (Chen, DeAngelis, & Angelaki, 2011; Grusser, Pause, & Schreiter, 1982). PIVC and areas 3a and 2v are heavily interconnected. Vestibular neurons also have been observed in the posterior parietal cortex; in area 7, in the ventral intraparietal area (VIP), the medial intraparietal area (MIP), and the medial superior temporal area (MST). VIP contains multimodal neurons involved in spatial coding. MIP and MST neurons respond to body motion through space by multisensory integration of visual motion and vestibular signals (Gu, DeAngelis, & Angelaki , 2007) and many MST cells are directly involved in heading perception (Gu, Watkins, Angelaki, & DeAngelis, 2006). Lesions of the parietal cortical areas can result in confusions in spatial awareness. Finally, areas involved with the control of saccades and pursuit eye movements, including area 6, area 8, and the superior frontal gyrus, receive vestibular signals (Fukushima, Sato, Fukushima, Shinmei, & Kaneko, 2000). How these different cortical regions contribute to our perception of motion and spatial orientation is still not well understood.

Spatial orientation and navigation

Our ability to know where we are and to navigate different spatial locations is essential for survival. It is believed that a cognitive map of our environment is created through exploration and then used for spatial orientation and navigation, such as driving to the store, or walking through a dark house (McNaughton, Battaglia, Jensen, Moser, & Moser, 2006). Cells in the limbic system and the hippocampus that contribute to these functions have been identified, including place cells, grid cells, and head direction cells (Figure 6B). Place cells in the hippocampus encode specific locations in the environment (O’Keefe, 1976). Grid cells in the entorhinal cortex encode spatial maps in a tessellated pattern (Hafting, Fyhn, Molden, Moser, & Moser, 2005). Head direction cells in the anterior-dorsal thalamus encode heading direction, independent of spatial location (Taube, 1995). It is thought that these cell types work together to provide for spatial orientation, spatial memory, and our ability to navigate. Both place cells and head direction cells depend upon a functioning vestibular system to maintain their directional and orientation information (Stackman, Clark, & Taube, 2002). The pathway by which vestibular signals reach the navigation network is not well understood; however, damage to the vestibular system, hippocampus, and dorsal thalamus regions often disrupts our ability to orient in familiar environments, navigate from place to place, or even to find our way home.

Motion sickness

Although a number of conditions can produce motion sickness, it is generally thought that it is evoked from a mismatch in sensory cues between vestibular, visual, and proprioceptive signals (Yates, Miller, & Lucot, 1998). For example, reading a book in a car on a winding road can produce motion sickness, whereby the accelerations experienced by the vestibular system do not match the visual input. However, if one looks out the window at the scenery going by during the same travel, no sickness occurs because the visual and vestibular cues are in alignment. Sea sickness, a form of motion sickness, appears to be a special case and arises from unusual vertical oscillatory and roll motion. Human studies have found that low frequency oscillations of 0.2 Hz and large amplitudes (such as found in large seas during a storm) are most likely to cause motion sickness, with higher frequencies offering little problems.

Summary

Here, we have seen that the vestibular system transduces and encodes signals about head motion and position with respect to gravity, information that is then used by the brain for many essential functions and behaviors. We actually understand a great deal regarding vestibular contributions to fundamental reflexes, such as compensatory eye movements and balance during motion. More recent progress has been made toward understanding how vestibular signals combine with other sensory cues, such as vision, in the thalamus and cortex to give rise to motion perception. However, there are many complex cognitive abilities that we know require vestibular information to function, such as spatial orientation and navigation behaviors, but these systems are only just beginning to be investigated. Future research regarding vestibular system function will likely be geared to seeking answers to questions regarding how the brain copes with vestibular signal loss. In fact, according to the National Institutes of Health, nearly 35% of Americans over the age of 40 (69 million people) have reported chronic vestibular-related problems. It is therefore of significant importance to human health to better understand how vestibular cues contribute to common brain functions and how better treatment options for vestibular dysfunction can be realized.