Spatial properties of central vestibular neurons

We studied the spatial characteristics of 45 vestibular-only (VO) and 12 vestibular-plus-saccade (VPS) neurons in two cynomolgus monkeys using angular rotation and static tilt. The purpose was to determine the contribution of canal and otolith-related inputs to central vestibular neurons whose activity is associated with the central velocity storage integrator. Lateral canal-related neurons responded maximally during vertical axis rotation when the head was tilted 25 +/- 6 and 22 +/- 3 degrees forward relative to the axis of rotation in the two animals, and vertical canal-related neurons responded maximally with the head tilted back 63+/- 5 and 57 +/- 7 degrees . The origin of the vertical canal-related input was verified by rotation about a spatial horizontal axis. Thirty-one percent of cells received input in a single canal plane. Sixty-seven percent of canal-related cells received otolith input, 31% of vertical canal neurons had lateral canal input, and 43% of lateral canal neurons had vertical canal input. Twenty percent of neurons had convergent input from the lateral canals, the vertical canals, and the otolith organs. Some VO and VPS cells had spatial-temporal convergent (STC) properties; more of these cells had STC properties at lower frequencies of rotation. Thus VO and VPS neurons associated with velocity storage receive a broad range of convergent inputs from each portion of the vestibular labyrinth. This convergence could provide the basis for gravity-dependent eye velocity orientation induced through velocity storage.     

Spatial properties of second-order vestibulo-ocular relay neurons in the alert cat

Second-order vestibular nucleus neurons which were antidromically activated from the region of the oculomotor nucleus (second-order vestibuloocular relay neurons) were studied in alert cats during whole-body rotations in many horizontal and vertical planes. Sinusoidal rotation elicited sinusoidal modulation of firing rates except during rotation in a clearly defined null plane. Response gain (spike/s/deg/s) varied as a cosine function of the orientation of the cat with respect to a horizontal rotation axis, and phases were near that of head velocity, suggesting linear summation of canal inputs. A maximum activation direction (MAD) was calculated for each cell to represent the axis of rotation in three-dimensional space for which the cell responded maximally. Second-order vestibuloocular neurons divided into 3 non-overlapping populations of MADs, indicating primary canal input from either anterior, posterior or horizontal semicircular canal (AC, PC, HC cells). 80/84 neurons received primary canal input from ipsilateral vertical canals. Of these, at least 6 received input from more than one vertical canal, suggested by MAD azimuths which were sufficiently misaligned with their primary canal. In addition, 21/80 received convergent input from a horizontal canal, with about equal number of type I and type II yaw responses. 4/84 neurons were HC cells; all of them received convergent input from at least one vertical canal. Activity of many vertical second-order vestibuloocular neurons was also related to vertical and/or horizontal eye position. All AC and PC cells that had vertical eye position sensitivity had upward and downward on-directions, respectively. A number of PC cells had MADs centered around the MAD of the superior oblique muscle, and 2/3 AC cells recorded in the superior vestibular nucleus had MADs near that of the inferior oblique. Thus, signals with spatial properties appropriate to activate oblique eye muscles are present at the second-order vestibular neuron level. In contrast, none of the second-order vestibuloocular neurons had MADs near those of the superior or inferior rectus muscles. Signals appropriate to activate these eye muscles might be produced by combining signals from ipsilateral and contralateral AC neurons (for superior rectus) or PC neurons (for inferior rectus). Alternatively, less direct pathways such as those involving third or higher order vestibular or interstitial nucleus of Cajal neurons might play a crucial role in the spatial transformations between semicircular canals and vertical rectus eye muscles.     

Response of vestibular neurons to head rotations in vertical planes. I. Response to vestibular stimulation

1. We have studied, in decerebrate cats, the responses of neurons in the lateral and descending vestibular nuclei to whole-body rotations in vertical planes that activated vertical semicircular canal and utricular receptors. Some neurons were identified as vestibulospinal by antidromic stimulation with floating electrodes placed in C4. 2. The direction of tilt that caused maximal excitation (response vector orientation) of each neuron was determined. Neuron dynamics were then studied with sinusoidal stimuli closely aligned with the response vector orientation, in the range 0.02-1 Hz. A few cells, for which we could not identify a response vector, probably had spatial-temporal convergence. 3. On the basis of dynamics, neurons were classified as receiving their input primarily from vertical semicircular canals, primarily from the otolith organs, or from canal+otolith convergence. 4. Response vector orientations of canal-driven neurons were often near +45 degrees or -45 degrees with respect to the transverse (roll) plane, suggesting these neurons received excitatory input from the ipsilateral anterior or posterior canal, respectively. Some neurons had canal-related dynamics but vector orientations near roll, presumably because they received convergent input from the ipsilateral anterior and posterior canals. Few neurons had their vectors near pitch. 5. In the lateral vestibular nucleus, neurons with otolith organ input (pure otolith or otolith+canal) tended to have vector orientations closer to roll than to pitch. In the descending nucleus the responses were evenly divided between the roll and pitch quadrants. 6. We conclude that most of our neurons have dynamics and response vector orientations that make them good candidates to participate in vestibulospinal reflexes acting on the limbs, but not those acting on the neck.     

Response characteristics of semicircular canal and otolith systems in cat. II. Responses of trochlear motoneurons

1. The electrical activity of single trochlear motoneurons (TMns) and axons of second order vestibular neurons presumably terminating on these motoneurons were studied during natural stimulation of semicircular canals and otolith organs in cats anesthetized with Ketamine. 2. Null point analysis showed that TMns received an excitatory canal input from the contralateral posterior canal, and labyrinthine lesion experiments suggested that the functionally synergistic, ipsilateral anterior canal provides an inhibitory input. A small number of motoneurons showed orthogonal canal convergence. 3. In addition to the canal projections most TMns received an otolithic input. Firing rate was proportional to lateral head tilt and was of the beta type. Most units also responded to pitch with an increase and decrease in firing rate on nose-up and nose-down positioning, respectively. Lesion experiments indicated that the otolith responses are the results of reciprocal innervation of TMns by contralateral (excitatory) and ipsilateral (inhibitory) otolith projections. 4. During sinusoidal rotation in yaw (canal only stimulation) the mean phase lag re acceleration of the response of TMns increased from 60 degrees at 0.025 Hz to 126 degrees at 1.0 Hz. In roll (canal plus otolith stimulation) the phase lag of TMn responses measured 180 degrees and 130 degrees at 0.025 and 1.0 Hz, respectively. Phase-lags measured in Vi and Vc axons were less by ca. 15 degrees. 5. The otolith contribution to TMn responses in roll was calculated by vectorial subtraction of the yaw from the roll responses: A phase lag of 10 (0.025 Hz) to 90 degrees (0.5 Hz) re. displacement was noted and gain was constant over the same range. Similar lag dynamics were revealed in TMns when studied during ramp displacement of the head. 6. The possible functional role of central canal-otolith convergence and the differences between the response of primary vestibular afferents and secondary vestibular neurons and TMns will be discussed.     

Otolith and canal integration on single vestibular neurons in cats

In this review, based primarily on work from our laboratory, but related to previous studies, we summarize what is known about the convergence of vestibular afferent inputs onto single vestibular neurons activated by selective stimulation of individual vestibular nerve branches. Horizontal semicircular canal (HC), anterior semicircular canal (AC), posterior semicircular canal (PC), utricular (UT), and saccular (SAC) nerves were selectively stimulated in decerebrate cats. All recorded neurons were classified as either projection neurons, which consisted of vestibulospinal (VS), vestibulo-oculospinal (VOS), vestibulo-ocular (VO) neurons, or non-projection neurons, which we simply term vestibular (V) neurons. The first three types could be successfully activated antidromically from oculomotor/trochlear nuclei and/or spinal cord, and the last type could not be activated antidromically from either site. A total of 1228 neurons were activated by stimulation of various nerve pair combinations. Convergent neurons were located in the caudoventral part of the lateral, the rostral part of the descending, and the medial vestibular nuclei. Otolith-activated vestibular neurons in the superior vestibular nucleus were extremely rare. A high percentage of neurons received excitatory inputs from two nerve pairs, a small percentage received reciprocal convergent inputs and even fewer received inhibitory inputs from both nerves. More than 30% of vestibular neurons received convergent inputs from vertical semicircular canal/otolith nerve pairs. In contrast, only half as many received convergent inputs from HC/otolith-nerve pairs, implying that convergent input from vertical semicircular canal and otolith-nerve pairs may play a more important role than that played by inputs from horizontal semicircular canal and otolith-nerve pairs. Convergent VS neurons projected through the ipsilateral lateral vestibulospinal tract (i-LVST) and the medial vestibulospinal tract (MVST). Almost all the VOS neurons projected through the MVST. Convergent neurons projecting to the oculomotor/trochlear nuclei were much fewer in number than those projecting to the spinal cord. Some of the convergent neurons that receive both canal and otolith input may contribute to the short-latency pathway of the vestibulocollic reflex. The functional significance of these convergences is discussed.     

Regional blood flow in genetically obese (ob/ob) mice

1. Experiments have been undertaken on 11 decerebrate cats to investigate the effects of natural vestibular stimulation on the activity of cerebellar fastigial neurons. 2. From recordings in the rostral portion of the nucleus during sinusoidal lateral (roll) and horizontal (yaw) rotation, distinctive patterns of response were observed. 3. The majority of neurons sensitive to vestibular stimulation showed responses to a single modality of vestibular activation. During lateral tilt some neurones showed positional sensititivy, others gave responses related tothe velocity of movement. Other neurones responded in phase with the velocity of movement in the horizontal plane. 4. Aside from these neuronal responses, others provided indications of a convergence of inputs from different sets of vestibular receptors. In particular, several neurons showed a pattern of response that indicated tht they received inputs from otolith receptors and ampullar receptors of the vertical canal. At low velocities of movement their response was positional but with inreasing velocity the magnitude of the response increased and there was a marked phase shift of the discharge towards head velocity. 5. Neurons responding to horizontal rotation often showed positional responses during lateral tilt. There were also indications of a convergence of ampullar inputs from both vertical and horizontal canals. 6. The neural pathways mediating these resonses are discussed in consideration of previous neuroanatomical and neurophysiological data. We consider it likely that several pathways may act to evoke the patterns of response observed, and a role of the cerebellar cortex is indicated.     

Patterns of canal and otolith afferent input convergence in frog second-order vestibular neurons

Second-order vestibular neurons (2 degrees VN) were identified in the isolated frog brain by the presence of monosynaptic excitatory postsynaptic potentials (EPSPs) after separate electrical stimulation of individual vestibular nerve branches. Combinations of one macular and the three semicircular canal nerve branches or combinations of two macular nerve branches were stimulated separately in different sets of experiments. Monosynaptic EPSPs evoked from the utricle or from the lagena converged with monosynaptic EPSPs from one of the three semicircular canal organs in ~30% of 2 degrees VN. Utricular afferent signals converged predominantly with horizontal canal afferent signals (74%), and lagenar afferent signals converged with anterior vertical (63%) or posterior vertical (37%) but not with horizontal canal afferent signals. This convergence pattern correlates with the coactivation of particular combinations of canal and otolith organs during natural head movements. A convergence of afferent saccular and canal signals was restricted to very few 2 degrees VN (3%). In contrast to the considerable number of 2 degrees VN that received an afferent input from the utricle or the lagena as well as from one of the three canal nerves (~30%), smaller numbers of 2 degrees VN (14% of each type of 2 degrees otolith or 2 degrees canal neuron) received an afferent input from only one particular otolith organ or from only one particular semicircular canal organ. Even fewer 2 degrees VN received an afferent input from more than one semicircular canal or from more than one otolith nerve (~7% each). Among 2 degrees VN with afferent inputs from more than one otolith nerve, an afferent saccular nerve input was particularly rare (4-5%). The restricted convergence of afferent saccular inputs with other afferent otolith or canal inputs as well as the termination pattern of saccular afferent fibers are compatible with a substrate vibration sensitivity of this otolith organ in frog. The ascending and/or descending projections of identified 2 degrees VN were determined by the presence of antidromic spikes. 2 degrees VN mediating afferent utricular and/or semicircular canal nerve signals had ascending and/or descending axons. 2 degrees VN mediating afferent lagenar or saccular nerve signals had descending but no ascending axons. The latter result is consistent with the absence of short-latency macular signals on extraocular motoneurons during vertical linear acceleration. Comparison of data from frog and cat demonstrated the presence of a similar organization pattern of maculo- and canal-ocular reflexes in both species.     

Response of pontomedullary reticulospinal neurons to vestibular stimuli in vertical planes. Role in vertical vestibulospinal reflexes of the decerebrate cat.

1. To investigate the neural substrate of vestibulospinal reflexes in decerebrate cats, we studied the responses of pontomedullary reticulospinal neurons to natural stimulation of the labyrinth in vertical planes. Our principal aim was to determine whether reticulospinal neurons that terminate in, or are likely to give off collaterals to, the upper cervical segments had properties similar to those of the vestibulocollic reflex (VCR). 2. Antidromic stimulation was used to determine whether the neurons projected to the neck, lower cervical, thoracic, or lumbar levels. Dynamics of the responses of spontaneously firing neurons were studied with sinusoidal stimuli delivered at 0.05-1 Hz and aligned to the plane of body rotation, that produced maximal modulation of the neuron (response vector orientation). Each neuron was assigned a vestibular input classification of otolith, vertical canal, otolith + canal, or spatial-temporal convergence (STC). 3. We found, in agreement with previous studies, that the largest fraction of pontomedullary reticulospinal neurons projected to the lumbar cord, and that only a small number ended in the neck segments. Neurons projecting to all levels of the spinal cord had similar responses to labyrinth stimulation. 4. Reticulospinal neurons that received only vertical canal inputs were rare (1 of 67 units). Most reticulospinal neurons (48%) received predominant otolith inputs, 18% received otolith + canal input, and only 9% had STC behavior. These data are in sharp contrast to the results of our previous studies of vestibulospinal neurons. A considerable portion of vestibulospinal neurons receives vertical canal input (38%), fewer receive predominantly otolith input (22%), whereas the proportion that have otolith + canal input or STC behavior is similar to our present reticulospinal data. 5. The response vector orientations of our reticulospinal neurons, particularly those with canal inputs (canal, otolith + canal, STC) were predominantly in the roll quadrants. There was no evidence of convergence of inputs from like canals across the midline (e.g., right anterior + left anterior). 6. Two characteristics of the VCR, STC behavior and bilateral input from symmetric vertical canals (in some muscles), cannot be accounted for by the reticulospinal neurons that we studied. Because these characteristics are also not seen in vestibulocollic neurons, they are likely to be the result of the appropriate convergence of vestibular signals in the spinal cord. 7. Pontomedullary reticulospinal neurons seem particularly well suited to play a role in gravity-dependent postural reflexes of neck and limbs.     

Fastigial nucleus activity during different frequencies and orientations of vertical vestibular stimulation in the monkey.

Neurons in the rostral part of the fastigial nucleus (FN) respond to vestibular stimulation but are not related to eye movements. To understand the precise role of these vestibular-only neurons in the central processing of vestibular signals, unit activity in the FN of alert monkeys (Macaca mulatta) was recorded. To induce vestibular stimulation, the monkey was rotated sinusoidally around an earth-fixed horizontal axis at stimulus frequencies between 0.06 (+/-15 degrees) and 1.4 Hz (+/-7.5 degrees). During stimulation head orientation was changed continuously, allowing for roll, pitch, and intermediate planes of orientation. At a frequency of 0.6 Hz, 59% of the neurons had an optimal response orientation (ORO) and a null response (i.e., no modulation) 90 degrees apart. The phase of neuronal response was constant except for a steep shift of 180 degrees around the null response. This group I response is compatible with a semicircular canal input, canal convergence, or a single otolith input. Several other features indicated more complex responses, including spatiotemporal convergence (STC). 1) For 35% of the responses at 0.6 Hz, phase changes were gradual with different orientations. Fifteen percent of these had a null response (group II), and 20% showed only a minimal response but no null response (group III). The remaining responses (6%), classified as group IV, were characterized by a constant sensitivity at different orientations in most instances. 2) For the vast majority of neurons, the stimulus frequency determined the response group, i.e., an individual neuron could show a group I response at one frequency and a group II (III or IV) response at another frequency. 3) ORO changed with frequency by >45 degrees for 44% of the neurons. 4) Although phase changes at different frequencies were close to head velocity (+/-45 degrees ) or head position (+/-45 degrees ) for most neurons, they exceeded 90 degrees for 29% of the neurons between 0.1 and 1.0 Hz. In most cases, this was a phase advance. The change in sensitivity with change in frequency showed a similar pattern for all neurons; the average sensitivity increased from 1.24 imp. s-1. deg-1 at 0.1 Hz to 2.97 imp. s-1. deg-1 at 1.0 Hz. These data demonstrate that only an analysis based on measurements at different frequencies and orientations reveals a number of complex features. They moreover suggest that for the vast majority of neurons several sources of canal and otolith information interact at this central stage of vestibular information processing.     

Velocity storage in the human vertical rotational vestibulo-ocular reflex

Human horizontal rotational vestibulo-ocular reflex (rVOR) has been extensively investigated: the horizontal semicircular canals sense yaw rotations with high-pass filter dynamics and a time constant (TC) around 5 s, yet the rVOR response shows a longer TC due to a central processing stage, known as velocity storage mechanism (VSM). It is generally assumed that the vertical rVOR behaves similarly to the horizontal one; however, VSM processing of the human vertical rVOR is still to be proven. We investigated the vertical rVOR in eight healthy human subjects using three experimental paradigms: (1) per- and post-rotatory around an earth-vertical axis (ear down rotations, EDR), (2) post-rotatory around an earth-horizontal axis with different stopping positions (static otolith stimulation), (3) per-rotatory around an earth-horizontal axis (dynamic otolith stimulation). We found that the TC of vertical rVOR responses ranged 3–10 s, depending both on gravity and on the direction of rotation. The shortest TC were found in response to post-rotatory earth-horizontal stimulation averaging 3.6 s, while they were prolonged in EDR stimulation, i.e. when the head angular velocity vector is aligned with gravity, with a mean value of about 6.0 s. Overall, the longest TC were observed in per-rotatory earth-horizontal stimulation, averaging 7.8 s. The finding of longer TC in EDR than in post-rotatory earth-horizontal stimulation indicates a role for the VSM in the vertical rVOR, although its contribution appears to be weaker than on the horizontal rVOR and may be directionally asymmetric. The results from per-rotatory earth-horizontal stimulation, instead, imply a role for the otoliths in controlling the duration of the vertical rVOR response. We found no reorientation of the response toward earth horizontal, indicating a difference between human and monkey rVOR.     

Low-frequency otolith and semicircular canal interactions after canal inactivation

During sustained constant velocity and low-frequency off-vertical axis rotations (OVAR), otolith signals contribute significantly to slow-phase eye velocity. The adaptive plasticity of these responses was investigated here after semicircular canal plugging. Inactivation of semicircular canals results in a highly compromised and deficient vestibulo-ocular reflex (VOR). Based on the VOR enhancement hypothesis, one could expect an adaptive increase of otolith-borne angular velocity signals due to combined otolith/canal inputs after inactivation of the semicircular canals. Contrary to expectations, however, the steady-state slow-phase velocity during constant velocity OVAR decreased in amplitude over time. A similar progressive decrease in VOR gain was also observed during low-frequency off-vertical axis oscillations. This response deterioration was present in animals with either lateral or vertical semicircular canals inactivated and was limited to the plane(s) of the plugged canals. The results are consistent with the idea that the low-frequency otolith signals do not simply enhance VOR responses. Rather, the nervous system appears to correlate vestibular sensory information from the otoliths and the semicircular canals to generate an integral response to head motion.     

Spatial properties of central vestibular neurons of monkeys after bilateral lateral canal nerve section

Thirty-seven neurons were recorded in the superior vestibular nucleus (SVN) of two cynomolgus monkeys 1-2 yr after bilateral lateral canal nerve section to test whether the central neurons had spatially adapted for the loss of lateral canal input. The absence of lateral canal function was verified with eye movement recordings. The relation of unit activity to the vertical canals was determined by oscillating the animals about a horizontal axis with the head in various orientations relative to the axis of rotation. Animals were also oscillated about a vertical axis while upright or tilted in pitch. In the second test, the vertical canals are maximally activated when the animals are tilted back about -50 degrees from the spatial upright and the lateral canals when the animals are tilted forward about 30 degrees . We reasoned that if central compensation occurred, the head orientation at which the response of the vertical canal-related neurons was maximal should be shifted toward the plane of the lateral canals. No lateral canal-related units were found after nerve section, and vertical canal-related units were found only in SVN not in the rostral medial vestibular nucleus. SVN canal-related units were maximally activated when the head was tilted back at -47 +/- 17 and -50 +/- 12 degrees (means +/- SD) in the two animals, close to the predicted orientation of the vertical canals. This indicated that spatial adaptation of vertical canal-related vestibular neurons had not occurred. There were substantial neck and/or otolith-related inputs activating the vertical canal-related neurons in the nerve-sectioned animals, which could have contributed to oculomotor compensation after nerve section.     

Response of vestibular neurons to head rotations in vertical planes. III. Response of vestibulocollic neurons to vestibular and neck stimulation

1. To compare the properties of the vestibulocollic reflex (VCR) with those of vestibular neurons projecting to the neck [vestibulocollic (VC) neurons], we have studied the behavior of the latter in the decerebrate cat. Neurons were identified by their antidromic responses to stimulation in C1-C2, but not C5. Responses to stimulation of vestibular and neck receptors were produced by rotation of the body and head in vertical planes. 2. We determined the plane of whole body (vestibular) or body with head counter-rotated (neck) rotation, which produced the maximal modulation of each neuron (response vector orientation). Neuron dynamics were then studied with sinusoidal (0.02-2 Hz) stimuli aligned with this orientation. 3. On the basis of dynamics and vector orientation, the neuron was assigned a vestibular input classification of otolith, vertical canal, otolith + canal, or spatial-temporal convergence (STC). 4. The properties of this sample of VC neurons are similar to those of a larger population of vestibular neurons whose projection was not identified. For example, the distributions of cells with different types of vestibular inputs were roughly the same; in particular, few cells showed STC responses. In addition, there was no evidence of significant convergence of like canals across the midline (e.g., right anterior + left anterior). 5. Also similar to the larger unidentified population, 80% of VC neurons tested for neck input received such an input. The neck and vestibular responses tended to be antagonistic; the vector orientations were usually opposite, and the response gains and phases similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

Directional sensitivity of anterior, posterior, and horizontal canal vestibulo-ocular neurons in the cat

Neurons subserving the vestibulo-ocular reflex transform the directionality and timing of input from semicircular canals into commands that are appropriate to rotate the eyes in a compensatory fashion. In order to assess the degree to which this transformation is evident in vestibular nucleus neurons of alert cats, we recorded the extracellular discharge properties of 138 second-order vestibular neurons in the superior and medial vestibular nucleus, including 64 neurons identified as second-order vestibulo-ocular neurons by antidromic responses to oculomotor nucleus stimulation and short-latency orthodromic responses to labyrinth stimulation (1.3 ms or less). Neuronal response gains and phases were recorded during 0.5-Hz sinusoidal oscillations about many different horizontal axes and during vertical axis rotations to define neuronal response directionality more precisely than in past studies. Neurons with spatial responses similar to anterior semicircular canal afferents were found to have more diverse maximal activation direction vectors than neurons with responses resembling those of posterior or horizontal canal afferents. The mean angle from neuron response vector to the axis of the nearest canal or canal pair was 19 degrees for anterior canal second-order neurons (n=28) and 20 degrees for anterior canal second-order vestibulo-ocular neurons (n=18), compared with 11 degrees for posterior canal second-order neurons (n=43) and 11 degrees for posterior canal second-order vestibulo-ocular neurons (n=25). Only two second-order vestibulo-ocular neurons (3%) showed a marked dependence of response phase on rotation direction, which is indicative of convergent inputs that differ in both dynamics and directionality. This suggests that spatiotemporal convergence is uncommon in the three-neuron vestibulo-ocular reflex arc of the cat. Neuron vectors included many that were closely aligned with canal axes and several that were better aligned with oblique or superior rectus extraocular muscle excitation axis vectors. Only single examples of second-order vestibulo-ocular neuron vectors were approximately aligned with the pitch and roll coordinate axes. We conclude that second-order vestibulo-ocular neurons do not exclusively represent either the semicircular canal sensory coordinate frame or the extraocular muscle excitation motor coordinate frame, and instead are mostly distributed on a continuum between the input and output coordinate frames, with anterior canal neurons having the widest distribution of directionality.     

The contribution of the horizontal semicircular canals to the response to off-vertical-axis rotation in the cat

Summary The response to off-vertical-axis rotation (OVAR) was measured in cats under circumstances in which the signals from the horizontal semicircular canals and otoliths were opposed. Opposition was achieved by sudden acceleration or deceleration during constant velocity OVAR. The degree of opposition was expressed as a canal/otolith ratio where a ratio of unity indicated agreement. For a canal/otolith ratio of 1, the OVAR gain (eye velocity/ stimulus velocity) was 0.73 (±0.13). The steady-state OVAR response was, however, reduced if the canals and otoliths were opposed. The reduction depended on the degree of opposition with a fall-off of 0.15 gain/(unit of canal/otolith ratio). These findings are discussed with respect to the central velocity store and the mechanism underlying the generation of the OVAR response.     

Timing of low frequency responses of anterior and posterior canal vestibulo-ocular neurons in alert cats

The pitch vertical vestibulo-ocular reflex (VOR) is accurate and symmetrical when tested in the normal upright posture, where otolith organ and central velocity storage signals supplement the basic VOR mediated by the semicircular canals. However, when the animal and rotation axis are together repositioned by rolling 90° to one side, head forward pitch rotations that excite the anterior semicircular canals elicit a more accurately timed VOR than do oppositely directed rotations that excite the posterior canals. This suggests that velocity storage of posterior canal signals is lost when the head is placed on its side. We recorded from 47 VOR relay neurons, second-order vestibulo-ocular neurons, of alert cats to test whether asymmetries are evident in the responses of neurons in the medial and superior vestibular nuclei during earth-horizontal axis rotations in the normal upright posture. Neurons were identified by antidromic responses to oculomotor nucleus stimulation and orthodromic responses to labyrinth stimulation, and were classified as having primarily anterior, posterior, or horizontal canal input based on response directionality. Neuronal response gains and phases were recorded during 0.5 Hz and 0.05 Hz sinusoidal oscillations in darkness. During 0.5 Hz rotations, anterior canal second-order vestibulo-ocular neurons responded approximately in phase with head velocity (mean phase re head position, ±SE, 80°±3°, n=18), as did posterior canal second-order vestibulo-ocular neurons (mean phase 81°±1°, n=25). Lowering the rotation frequency to 0.05 Hz resulted in only slight advances in response phases of individual anterior canal second-order vestibulo-ocular neurons (mean phase 86°±6°, mean advance 7°±5°, n=12). In contrast, posterior canal second-order vestibulo-ocular neurons behaved more like semicircular canal afferents, with responses markedly phase-advanced (mean advance 28°±5°, n=14) by lowering rotation frequency to 0.05 Hz (mean phase 111°±5°, n=14). In summary, low frequency responses of anterior and posterior canal second-order vestibulo-ocular neurons recorded during horizontal axis pitch correspond to the VOR they excite during vertical axis pitch. These results show that velocity storage is evident at anterior but not posterior canal second-order vestibulo-ocular neurons. We conclude that responses of posterior canal second-order vestibulo-ocular neurons are insufficient to explain the accurate low frequency VOR phase observed during backward head pitch in the upright posture, and that velocity storage or otolith signals required for VOR accuracy are carried by other neurons. Electronic Publication     

Human 3-D aVOR with and without otolith stimulation

We describe in detail the frequency response of the human three-dimensional angular vestibulo-ocular response (3-D aVOR) over a frequency range of 0.05-1 Hz. Gain and phase of the human aVOR were determined for passive head rotations in the dark, with the rotation axis either aligned with or perpendicular to the direction of gravity (earth-vertical or earth-horizontal). In the latter case, the oscillations dynamically stimulated both the otolith organs and the semi-circular canals. We conducted experiments in pitch and yaw, and compared the results with previously-published roll data. Regardless of the axis of rotation and the orientation of the subject, the gain in aVOR increased with frequency to about 0.3 Hz, and was approximately constant from 0.3 to 1 Hz. The aVOR gain during pitch and yaw rotations was larger than during roll rotations. Otolith and canal cues combined differently depending upon the axis of rotation: for torsional and pitch rotations, aVOR gain was higher with otolith input; for yaw rotations the aVOR was not affected by otolith stimulation. There was a phase lead in all three dimensions for frequencies below 0.3 Hz when only the canals were stimulated. For roll and pitch rotations this phase lead vanished with dynamic otolith stimulation. In contrast, the horizontal phase showed no improvement with additional otolith input during yaw rotations. The lack of a significant otolith contribution to the yaw aVOR was observed when subjects were supine, prone or lying on their sides. Our results confirm studies with less-natural stimuli (off-vertical axis rotation) that the otoliths contribute a head-rotation signal to the aVOR. However, the magnitude of the contribution depends on the axis of rotation, with the gain in otolith-canal cross-coupling being smallest for yaw axis rotations. This could be because, in humans, typical yaw head movements will stimulate the otoliths to a much lesser extent then typical pitch and roll head movements.     

Otolith-semicircular canal interaction during postrotatory nystagmus in humans

The otolith-semicircular canal interaction during postrotatory nystagmus was studied in ten normal human subjects by applying fast, short-lasting, passive head and body tilts (15, 30, 45, or 90° in the roll or pitch plane) 2 s after sudden stop from a constant-velocity rotation (100°/s) about the earth-vertical axis in yaw. Eye movements were measured with three-dimensional magnetic search coils. Following the head tilt, activity in the semicircular canal primary afferents continues to reflect the postrotatory angular velocity vector in head-centered coordinates, whereas otolith primary afferents signal a different orientation of the head relative to gravity. Despite the change in head orientation relative to gravity, postrotatory eye velocity decayed closely along the axis of semicircular canal stimulation (horizontal in head coordinates) for large head tilts (90°) and also for small head tilts (15–45°) for reorientations in the pitch plane. Only for small head tilts (15–45°) in the roll plane was there a reorientation of the eye rotation axis toward the gravitational vector. This reorientation was approximately compensatory for 15° head tilts. For 30° and 45° head tilts the eye rotation axis tilted toward the gravitational vector by about the same amount as for 15° head tilts. These results suggest that, with the exception of small head tilts in the roll plane, there was no compelling data showing a relationship between the eye rotation axis and head tilt and that postrotatory nystagmus is largely organized in head-centered rather than gravity-centered coordinates in humans. This indicates a rudimentary, nonlinear, and direction-specific interaction of semicircular canal and otolith signals in the central vestibular system in humans.     

The effect of gravity on the horizontal and vertical vestibulo-ocular reflex in the rat

Horizontal and vertical eye movements were recorded in alert pigmented rats using chronically implanted scleral search coils or temporary glue-on coils to test the dependence of the vestibulo-ocular reflex (VOR) upon rotation axis and body orientation. The contributions of semicircular-canal versus otolith-organ signals to the VOR were investigated by providing canal-only (vertical axis) and canal plus otolith (horizontal axis) stimulation conditions. Rotations that stimulated canals only (upright yaw and nose-up roll) produced an accurate VOR during middle- and high-frequency rotations (0.2-2 Hz). However, at frequencies below 0.2 Hz, the canal-only rotations elicited a phase-advanced VOR. The addition of a changing gravity stimulus, and thus dynamic otolith stimulation, to the canal signal (nose-up yaw, on-side yaw, and upright roll) produced a VOR response with accurate phase down to the lowest frequency tested (0.02 Hz). In order to further test the dependence of the VOR on gravitational signals, we tested vertical VOR with the head in an inverted posture (inverted roll). The VOR in this condition was advanced in phase across all frequencies tested. At low frequencies, the VOR during inverted roll was anticompensatory, characterized by slow-phase eye movement in the same direction as head movement. The substantial differences between canalonly VOR and canal plus otolith VOR suggest an important role of otolith organs in rat VOR. Anticompensatory VOR during inverted roll suggests that part of the otolith contribution arises from static tilt signals that are inverted when the head is inverted.     

Vestibular signals in the parasolitary nucleus

Vestibular primary afferents project to secondary vestibular neurons located in the vestibular complex. Vestibular primary afferents also project to the uvula-nodulus of the cerebellum where they terminate on granule cells. In this report we describe the physiological properties of neurons in a "new" vestibular nucleus, the parasolitary nucleus (Psol). This nucleus consists of 2,300 GABAergic neurons that project onto the ipsilateral inferior olive (beta-nucleus and dorsomedial cell column) as well as the nucleus reticularis gigantocellularis. These olivary neurons are the exclusive source of vestibularly modulated climbing fiber inputs to the cerebellum. We recorded the activity of Psol neurons during natural vestibular stimulation in anesthetized rabbits. The rabbits were placed in a three-axis rate table at the center of a large sphere, permitting vestibular and optokinetic stimulation. We recorded from 74 neurons in the Psol and from 23 neurons in the regions bordering Psol. The activity of 72/74 Psol neurons and 4/23 non-Psol neurons was modulated by vestibular stimulation in either the pitch or roll planes but not the horizontal plane. Psol neurons responded in phase with ipsilateral side-down head position or velocity during sinusoidal stimulation. Approximately 80% of the recorded Psol neurons responded to static roll-tilt. The optimal response planes of evoked vestibular responses were inferred from measurement of null planes. Optimal response planes usually were aligned with the anatomical orientation of one of the two ipsilateral vertical semicircular canals. The frequency dependence of null plane measurements indicated a convergence of vestibular information from otoliths and semicircular canals. None of the recorded neurons evinced optokinetic sensitivity. These results are consistent with the view that Psol neurons provide the vestibular signals to the inferior olive that eventually reached the cerebellum in the form of modulated climbing fiber discharges. These signals provide information about spatial orientation about the longitudinal axis.