Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas 77555-1063
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ABSTRACT |
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Kaufman, Galen D., Michael E. Shinder, and Adrian A. Perachio. Convergent Properties of Vestibular-Related Brain Stem Neurons in the Gerbil. J. Neurophysiol. 83: 1958-1971, 2000. Three classes of vestibular-related neurons were found in and near the prepositus and medial vestibular nuclei of alert or decerebrate gerbils, those responding to: horizontal translational motion, horizontal head rotation, or both. Their distribution ratios were 1:2:2, respectively. Many cells responsive to translational motion exhibited spatiotemporal characteristics with both response gain and phase varying as a function of the stimulus vector angle. Rotationally sensitive neurons were distributed as Type I, II, or III responses (sensitive to ipsilateral, contralateral, or both directions, respectively) in the ratios of 4:6:1. Four tested factors shaped the response dynamics of the sampled neurons: canal-otolith convergence, oculomotor-related activity, rotational Type (I or II), and the phase of the maximum response. Type I nonconvergent cells displayed increasing gains with increasing rotational stimulus frequency (0.1-2.0 Hz, 60°/s), whereas Type II neurons with convergent inputs had response gains that markedly decreased with increasing translational stimulus frequency (0.25-2.0 Hz, ±0.1 g). Type I convergent and Type II nonconvergent neurons exhibited essentially flat gains across the stimulus frequency range. Oculomotor-related activity was noted in 30% of the cells across all functional types, appearing as burst/pause discharge patterns related to the fast phase of nystagmus during head rotation. Oculomotor-related activity was correlated with enhanced dynamic range compared with the same category that had no oculomotor-related response. Finally, responses that were in-phase with head velocity during rotation exhibited greater gains with stimulus frequency increments than neurons with out-of-phase responses. In contrast, for translational motion, neurons out of phase with head acceleration exhibited low-pass characteristics, whereas in-phase neurons did not. Data from decerebrate preparations revealed that although similar response types could be detected, the sampled cells generally had lower background discharge rates, on average one-third lower response gains, and convergent properties that differed from those found in the alert animals. On the basis of the dynamic response of identified cell types, we propose a pair of models in which inhibitory input from vestibular-related neurons converges on oculomotor neurons with excitatory inputs from the vestibular nuclei. Simple signal convergence and combinations of different types of vestibular labyrinth information can enrich the dynamic characteristics of the rotational and translational vestibuloocular responses.
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INTRODUCTION |
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Second-order neurons of the vestibular system
(vestibular nuclei neurons) have been demonstrated to respond to inputs
from multiple sensory organs of the labyrinth. This type of convergence has been proposed to explain a phenomenon originally named
spatiotemporal convergence by Baker et al. (1984),
whereby neuronal response gains and phases were found to vary
systematically when head tilts were applied dynamically in each of
several vertical head planes. Coactivation of semicircular canal and
macular receptors (canal-otolith convergence) was proposed as the
mechanism that accounted for the finding that responses varied as a
function of head tilt angle.
In subsequent studies, in which pure translational acceleration was
applied by horizontal translational motion of the head, a similar
response was reported for second-order medial vestibular neurons in
decerebrate rats (Angelaki et al. 1993; Bush et
al. 1993
). This form of spatiotemporal convergence was modeled
by the probable convergence of inputs from otolith organ-related afferent neurons with different response dynamics, i.e., vector sensitivities or firing regularity (Angelaki 1993
).
Furthermore, medial vestibular neurons exhibited responses that
appeared to encode different stimulus properties. For example, in some
neurons the responses to stimulus vectors to which they were maximally sensitive remained in-phase with peak head acceleration and exhibited relatively constant gains across stimulus frequencies. In contrast, the
responses to an orthogonal vector that resulted in minimal amplitude
gain were characterized by a response phase lead of nearly 90°.
However, this minimum response gain increased in magnitude ~10-fold
over a decade increase in stimulus frequency. Those properties can be
compared with the two forms of vestibuloocular responses to applied
linear forces. The neuronal responses to the vector of maximum
sensitivity best relate to the compensatory vestibuloocular response to
static head tilt, which is dominated by low-pass characteristics (Tomko and Paige 1992
). In contrast the vestibuloocular
responses to dynamic translational acceleration have high-pass
properties that reflect sensitivity to the rate of change of
acceleration (jerk) during translational motion (Niven et al.
1966
), similar to that found in neuronal responses to the
vector of minimum sensitivity.
Among the other premotor inputs to oculomotor neurons are those from
the perihypoglossal nuclei (including the prepositus, Rollers nucleus,
and intercalatus), particularly the prepositus nucleus, which itself
has reciprocal connections with the medial, inferior, and ventral
lateral vestibular nuclei bilaterally (Belknap and McCrea
1988; McCrea and Baker 1985
). The vestibular
responses of perihypoglossal neurons have been examined to date
primarily with regard to stimulation of horizontal semicircular canal
receptors. The majority of the responses of those cells were classified
as Type II activated by contraversive rotation (Blanks et al.
1977
; McFarland and Fuchs 1992
). Because the
vast majority of medial vestibular nuclei cells receive convergent
canal and otolith organ-related inputs (Bush et al.
1993
), it is presumed that many of those cells project to the
perihypoglossal area and thus would impart signals from both vestibular
sources onto their target neurons. Perihypoglossal neurons also have
been found to discharge during eye movements (McFarland and
Fuchs 1992
). Typically, they have been found to burst before
the onset of saccades and/or exhibit sensitivity to ocular position
(Escudero et al. 1996
; McFarland and Fuchs 1992
). A subset of those cells also responds to head rotation.
Perihypoglossal neurons projecting to the abducens nuclei have been
characterized immunocytochemically as GABAergic (Lahjouji et al.
1997) and glycinergic (Spencer et al. 1989
).
Vestibular-related output of those cells therefore would be sign
reversed compared with that of converging vestibular nuclei inputs to
oculomotor neurons. We hypothesize that signal cancellation might occur
at the oculomotor neuron unless the perihypoglossal neurons' dynamic responses are different from those of the vestibular nuclei. More complete characterization of the vestibular properties of
perihypoglossal cells would provide potential insight as to the role of
those cells in regulation of vestibuloocular function.
One of the objectives of the current study was to examine vestibular- and oculomotor-related activity in and near the perihypoglossal neurons during the application of either horizontal rotational or translational head acceleration. We then compared the results to previous findings in similar studies of medial vestibular nucleus neurons to assess how both sets of premotor neurons might influence and regulate the rotational and translational vestibuloocular responses.
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METHODS |
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For measurement of extracellular unit activity and the vestibuloocular reflex (VOR), we developed an alert gerbil preparation in which orthodromic vestibular labyrinth stimulating electrodes, a recording access cap, and a head restraint bolt were implanted surgically several days before the first recording session. Under general anesthesia [pentobarbital sodium (Nembutal) and ketamine, each 20 mg/kg], a postauricular approach through the thin bulla was used uni- or bilaterally to place silver monopolar stimulating electrodes near the oval window. Self-tapping stainless steel screws and inverted T-bolts were placed into the skull at several points as anchors for the acrylic cap, which fixed the hardware together. After the surgery and for the extent of its use, each animal was housed individually to protect the implant. These and all other procedures were reviewed and approved by the University of Texas Medical Branch Institutional Animal Care and Utilization Committee.
On a recording day, the animal was anesthetized briefly with isoflurane gas (3% induction, 1% maintenance) while an eye coil (see following text) was secured to the locally anesthetized cornea of one eye. The animal was allowed to recover from the isoflurane while restrained. The head was fixed by holding the skull-cap restraint stud in a plane that brings the horizontal semicircular canals to an earth horizontal position (20° nose down). The body was confined loosely in a plexiglass tube the diameter of which slightly exceeded the animal's body. Within 5 to 10 min the gerbil became alert. We have determined that by 30 min after isoflurane anesthesia, the gerbil VOR recovers and remains stable. Therefore at 30 min we began to obtain a record of horizontal and translational VOR at several frequencies and began simultaneous extracellular unit recordings in the perihypoglossal region. Horizontal translational acceleration angles were defined with the right-hand rule so that positive values represent an acceleration vector pointing out the animal's left ear.
Using these techniques it was possible to perform multiple recording sessions with individual animals approximately biweekly spanning several weeks. At the end of the terminal experiment, a glass pipette containing saturated Fast Green dye in 2 M KCl was advanced into the perihypoglossal region. Cell latency was determined by applying 100-µs pulses to the oval window electrode. Both polarities were tested for the maximum effect, and the current was decreased to determine a 50% threshold where the cell fired after about half of the pulses. The threshold current was typically 25-50 µA. The reference electrode was subcutaneous in the neck region. After a representative unit was found and characterized, cathodal (positive) DC (+10 µA for 10-15 min) was applied to the recording electrode to eject the Fast Green dye. After the experiments, the animal was anesthetized deeply using 17% intraperitoneal chloral hydrate and perfused transcardially with 4% paraformaldahyde. The brain stem was removed and cut in 40-µm frozen sections for electrode track and dye spot recovery. The Fast Green requires no further processing and can be seen clearly in unstained or lightly counterstained tissue (see Fig. 2).
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Using aseptic technique, the acrylic skull caps used in our experiments for restraint and brain stem extracellular recording access were stable for several weeks without antibiotics or other preventative treatments. One animal was maintained with a skull cap for 6 wk with no behavioral pathology. However, after perfusion, the tissue over the recording site was thickened and fibrous, and the surface of the cerebellum was concave where repeated electrode entry was performed. Significant cerebellar compression and pathology were present. Therefore an optimum period for experimental manipulation using these methods is ~2 wk with no more than three to four separate recording days. Baseline data were collected during the first recording sessions, while anatomic and/or adaptive experiments could be performed during the terminal recording day, with subsequent tissue collection.
Some early data were acquired in the decerebrate preparation for
comparison. The technique in the gerbil has been described previously
(Newlands and Perachio 1990a,b
). There was a clear difference in unit activity between the decerebrate and alert preparations. This generally was characterized by lower background discharge rates and response gains across frequencies in the
decerebrate animal (P = 0.0001, ANOVA). In addition,
variations from the alert sample were common. At 1.0 Hz, for example,
rotational convergent neurons in the decerebrate preparation
significantly phase-led their counterparts as observed in alert
preparations (P = 0.034). Nonconvergent,
eye-independent Type I decerebrate cells had an especially strong phase
shift with increasing stimulus frequency.
SEARCH-COIL TECHNIQUE.
We adopted the technique of Hess and Dieringer (1991) to
record two-dimensional eye movements in the gerbil. Briefly, an eye coil (Sokymat, Switzerland; 1.8 mm, 80 turns) was glued onto the cornea
using cyanoacrylate adhesive while the gerbil was maintained under
isoflurane anesthesia. The eye was held open with a tungsten wire
speculum and irrigated with a viscous topical anesthetic (lidocaine,
2%) before allowing the animal to become alert. Calibration of the eye
coil was accomplished by physically moving the attached coil through
rotational horizontal and vertical steps of the eye against a small
protractor while the animal was still under anesthesia or by
horizontally rotating the head of the anesthetized animal. After the
recording session, excess topical anesthetic was applied to the eye,
and the coil was removed with a gentle shearing motion. No significant
damage occurred to the cornea from this procedure, which could be
repeated in the same eye after 2-3 days. The signal derived by the
calibration procedure was linear over a range of ±30° for horizontal
displacement and ±20° for vertical displacement. Vision in the eye
to which the coil was attached probably was reduced.
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RESULTS |
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General trends and distributions
The combined data represent 223 neurons in and near the
perihypoglossal region of alert (n = 13) and
decerebrate (n = 15) gerbils (total n = 28). A summary of response types is presented in Table 1. The
distribution is based on units recorded in that region and separated by
canal-otolith convergence and horizontal vestibular rotational Type.
Type I neurons are defined as responding to ipsilateral rotations, Type
II to contralateral rotation, Type III to both, and Type IV to neither
(Duensing and Schaeffer 1958). Note that a much higher
cell yield was obtained in the alert preparation. More units were
recorded on each day (the animal was more stable) and over days several
recording sessions were possible.
Stereotaxic distribution
The approximate stereotaxic distribution of the presented cells is shown in Fig. 1. The region includes the medial MVe, the prepositus nucleus, the intercalatus and Roller's nucleus caudally, the medial longitudinal fasciculus, and dorsal cells of the reticular medullary region. Stereotaxic data were verified histologically with electrode tracts and dye spots in sectioned brain stem tissue (Fig. 2). No significant unit response differences based on anatomic location were found, although we did not systematically vary stereotaxic position. Because no significant relationships were found between physiological and anatomic properties, we focused on the significant variables and interactions described in the following text. The majority of recorded cells were located in the rostral half of the prepositus region.
Latency from labyrinth
Galvanic labyrinth stimulation was applied to test the responses
of some of the cells to determine their latency and synaptic relationship to the vestibular periphery. Neurons in the prepositus nucleus, the location of which was verified later with Fast Green dye
spots, had latencies ranging from 1.5-4 ms. These latencies indicate
di- and polysynaptic connections to either or both the ipsilateral and
contralateral labyrinth (Newlands and Perachio 1990a).
This supports the functional position of these cells as primarily third
order from the labyrinth.
Finally the sampled population was cells with irregular firing characteristics (coefficient of firing variation, CV > 0.3). Rotational-only neurons had a significantly higher CV than their canal-otolith convergent counterparts (1.4 ± 0.85 vs. 1.1 ± 0.55, means ± SD; P = 0.023, F = 5.345, ANOVA). The vast majority of the cells in this region had a response to passive head motion in some form.
Results by category
We categorized the cells by examining several of their functional attributes and found the tested population to be highly heterogenous. No clear grouping of cell types with several similar characteristics was observed. Rather we encountered a mixture of cells with a variety of individual patterns of these attributes.
Rotational responses were tested across frequencies and classified according to the following attributes: rotational response Type (I or II), the presence of otolith convergence (canal-otolith convergence), the presence of an oculomotor-related response (nystagmus related activity), and finally a classification of the response phase. We arbitrarily defined a cell to be "in phase" or "out of phase" if the cycle phase angle of that cell's maximum firing response occurred within or outside of ±45° relative to the peak stimulus (re: peak acceleration for translational stimuli or re: peak velocity for rotational stimuli).
The attributes of the translational response in canal-otolith convergent cells, and in purely translational cells, also were categorized. Translational response parameters included the following: whether the cell was canal-otolith convergent and if so, its rotational vestibular Type (I or II), the presence of an oculomotor-related response (nystagmus or translational VOR related activity), the classification of the response phase (in or out re: acceleration), and finally whether the cell had additional spatiotemporal convergent properties (i.e., a non-null minimum response or Smin and shifting gain and phase with stimulus vector orientation). This latter determination could be made by testing across different polar angles of stimulus vector orientation. All of the translational vectors were parallel to the Earth's horizontal plane.
Clearly all of these unique attributes could combine in many patterns. The majority of the unit data were canal-otolith convergent and revealed in-phase responses. Translational-only neurons more likely had responses that were out of phase, and those cells generally had a higher response gain than in-phase translational-only neurons. Each category included cells for which individual patterns of attributes differed, and a particular attribute could be observed across many categories. For example, oculomotor-related neurons occurred in all of the categorical divisions. The response gain also varied greatly within one category.
The number of factors tested meant that the actual number of recorded neurons that could be placed into any one particular combination of attributes was sometimes low. However, by employing variance analysis methods we gained an appreciation of which factors and interactions of factors were most important in shaping the response of neurons in this region. Multivariate ANOVA (MANOVA) was performed on the rotational and translational gain and phase data separately. The results from this analysis will be used to support classification response differences in the figures to follow. Pair-wise comparisons (contrasts) also are reported as P values throughout RESULTS to support specific observations. These data were a subset of the factors shown to be significant by the overall MANOVA.
Data illustrated in Figs. 4 and 5 were derived from a subset of the total data summarized in Table 1, omitting decerebrate, Type III, and any data obtained in tests in which the peak stimulus was not either ±0.1 g or 60°/s. One hundred and sixty-four cells remained for analysis of data from the alert preparation.
Ocular VOR responses
The presence of an earth-stationary visual surround slightly increased the rotational response gain of the VOR above that observed in the dark. Horizontal rotational VOR gains were generally <0.6 in the light and increased with stimulus frequency. Figure 3 shows an example of calculated rotational and translational VOR gain and phase at several frequencies in one animal.
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The translational horizontal VOR (tVOR) maximum ocular response gain varied with the stimulus vector polar angle. In general, the horizontal tVOR ocular gain was maximal when the vector of horizontal acceleration was oriented orthogonally to the optic axis (~50° from the nasooccipital axis). Vertical eye movements were maximal near horizontal translations near the optic axis. Torsional eye movements were not recorded. Individual animal responses always revealed a sinusoidal pattern the amplitude of which varied with stimulus polar angle. The translational VOR was characterized by a gain increase and advancing phase with increasing stimulus frequency (Fig. 3).
Rotational unit responses
ROTATIONAL TYPE AND CANAL-OTOLITH CONVERGENCE.
All of the four rotational response types as defined by Duensing
and Schaeffer (1958) were found in cellular responses encoded in the perihypoglossal region. Fifty-five percent of the cells with a
response to horizontal rotation (Types I, II, or III) were vestibular
Type II (sensitive to contralateral rotation). Type I (ipsilateral
sensitivity) and III (bidirectional sensitivity) cells constituted 35 and 9%, respectively, of the responsive neurons (Table 1). This
distribution remained fairly stable across classifications.
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OCULOMOTOR-RELATED RESPONSES. Eye movements during applied motion were correlated with simultaneous unit recordings. Within the tested neurons a continuum of response dynamics was observed, including pure vestibular responses (no oculomotor-related activity), and cells with both head-motion and oculomotor-related sensitivity. The paucity of spontaneous eye movement in the gerbil, along with the lack of behaviorally trained visuomotor responses (e.g., fixation or saccades to visual targets), precluded detailed evaluation of oculomotor related activity or ocular-position sensitivity. Nevertheless the presence or absence of an oculomotor-related signal associated with the vestibuloocular fast phases was one of several significant factors accounting for differences in response gain across many cell categories.
The second view of the rotational data (Fig. 4-2) splits neurons by their response or lack of response to oculomotor activity during the horizontal VOR. Neurons shown to burst or pause in correlation with the fast phase of nystagmus were classified as oculomotor-related, and separated further by Type I and II responses. Thirty percent (30%) of the rotational vestibular neurons had oculomotor-related activity. Of these, 72% (n = 42) had Type II rotational responses. However, most of the high-pass rotational frequency response was attributable to rotational-only Type I, not Type II, neurons (Fig. 4, 1 and 2). Neurons with oculomotor-related sensitivity had higher rotational gains than neurons in the same rotational response category that did not exhibit oculomotor-related activity (Fig. 4-2, P = 0.03). At least one pattern of cell attributes was commonly observed. In 16% of vestibular-related neurons in the alert preparation, the cells responded to contralateral (Type II) head rotation, burst with ipsilateral ocular fast phases and paused with fast phases in the opposite direction. That is, bursting correlated with ipsilateral fast phases during the portion of the stimulus cycle in which the vestibular canal input diminished, whereas brief pauses of unit activity occurred during the rotational vestibular response to contraversive head rotation associated with fast ocular motion in the direction opposite to the recording side (see Fig. 6). Bursting typically preceded the onset of the fast phase eye movement by ~10 ms.
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PHASE CLASSIFICATION. The third view of the rotational data (Fig. 4-3) separates Type I and II neurons by their phase response classification (in phase = less than ±45° vs. out of phase = more than ±45°). There was significant variation in the cyclic phase relationship between the maximum neuronal response gain and the maximum sinusoidal stimulus amplitude during rotational stimuli. Using the two categories of response phase classification, a distinct difference could be observed in the response gain (MANOVA, P = 0.016, power = 0.67, Fig. 4-3). Neurons in which rotational response gains increased with increasing stimulus frequency were characterized by in-phase responses. In addition, their activity was often also oculomotor-related, and their vestibular responses were statistically mostly nonconvergent, Type I responses to head rotation (see Fig. 4, 1-3).
Translational unit responses
CANAL-OTOLITH CONVERGENCE AND ROTATIONAL TYPE. We observed neurons with translational-only, rotational-only, and canal-otolith convergent responses in a 1:2:2 ratio (see Table 1). The response gains during translational motion decreased with increasing stimulus frequency (low-pass characteristics, Fig. 5), but only for some categories.
The first view of the translational data (Fig. 5-1) shows the translational response gain across stimulus frequency of canal-otolith convergent neurons (both Type I and Type II), with translational-only neurons. Type II canal-otolith convergent neurons had higher response gains at 0.25 Hz than Type I and nonconvergent (translational-only) cells (P = 0.0095). The translational response gain of nonconvergent cells had only slight low-pass characteristics. This low-pass characteristic often was observed in convergent Type II neurons. Compared with the rotational response of Type I neurons, the vestibular rotational types, I and II, appear to complement each other in their frequency sensitivity to semicircular canal or otolith organ stimulation. The second view (Fig. 5-2) separates the translational responses of Type I and II canal-otolith convergent neurons and translational-only neurons by the presence of an oculomotor-related signal. The oculomotor-related classification was assigned to neurons with rotation-induced, nystagmus-related bursting activity. However, we did observe unit responses during translational motion that correlated with fast phases of the translational response. These neurons also exhibited bursting behavior during the rotational VOR. Figure 5-2 shows that it was primarily the oculomotor-related Type II neurons that were responsible for the low-pass characteristic. Oculomotor-related translational neurons had a significantly greater response gain than their vestibular-only counterparts (MANOVA P = 0.03, power = 0.58) Note that both the rotational and translational VOR responses reveal high pass activity (Fig. 3), yet a significant subset of perihypoglossal neurons encode low-pass activity. This apparent discrepancy is incorporated in a model presented in the discussion.PHASE CLASSIFICATION AND SPATIOTEMPORAL CONVERGENCE.
Convergent input from both regularly and irregularly firing vestibular
afferent neurons (Goldberg et al. 1987) arguably results in what has been referred to as two-dimensional responses to
stimulation of the otolith organs (Angelaki 1993b
;
Bush et al. 1993
). More than half of the neurons we
encountered that responded to pure translational acceleration displayed
this type of spatiotemporal convergence, i.e., a nonzero minimum
response gain (Smin) and a maximum
response phase that varied as a function of the stimulus vector angle
of horizontal translational motion (see Fig.
7). The phase relationship usually
inverts at a polar angle near the Smin
but varies systematically on either side. The resulting response gain
appears elliptical-, hourglass-, or dumbbell-shaped when plotted over
360° in the stimulus plane. The width of the ellipse varies greatly
depending on the ratio of the maximum and minimum response angle
(Smax/Smin).
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DISCUSSION |
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Our results indicate that neurons in the perihypoglossal region of the gerbil receive highly convergent (canal-otolith, spatiotemporal, and oculomotor) inputs in variable patterns. The convergence of otolith and canal signals was coincident with lower high-frequency horizontal rotational gains and higher low-frequency translational gains (see Figs. 4 and 5). The translational low-pass characteristic of canal-otolith convergent units was carried often on Type II neurons (Fig. 5). Nonconvergent neurons with a Type I rotational response displayed significantly higher rotational gains at frequencies above 1 Hz compared with convergent Type I and all Type II neurons.
Cells with an oculomotor-related signal displayed higher rotational gains over all frequencies tested, especially at higher frequencies, and had higher translational gains at lower frequencies, than their vestibular-only counterparts. Oculomotor-related neuronal response gains also varied as a function of stimulus frequency to a greater extent than vestibular-only units.
However, these patterns had many exceptions. It would be an oversimplification to conclude that there were two primary neuron behaviors. The data indicate a diffuse relationship among neuron categories, with individual units possessing nontypical patterns of response dynamics. Only by examination of the entire sample of cells and applying MANOVA did the observed trends emerge.
Finally we confirmed that the reduced decerebrate preparation is not an accurate representation of normal function. These findings support the notion that the perihypoglossal and surrounding regions are an anatomic and functional extension of the MVe, combining multiple signals on many neuron types. The data suggest that this region could serve diverse multimodal transformations in the CNS.
Comparison with MVe neurons
MVe neurons are known to display spatiotemporal convergence properties that are characterized by response gains and phases that vary continuously throughout a range of stimulus vectors. During horizontal head rotations, both Type I and II neurons in the MVe display a phase relationship with head velocity that leads by 20-30° at 0.15 Hz and becomes virtually in-phase at higher frequencies.
Burst-position neurons in the primate marginal zone [on the border of
prepositus hypoglossi (PrH) and MVe] have been shown to be one source
of a horizontal eye position signal (McFarland and Fuchs
1992). Our findings reveal that translational
vestibular-related responses, although similar to MVe neurons, possess
orthogonal response phase properties that could control eye movement
during specific types of head motion. We suggest that prepositus
neurons, by virtue of their responses to vestibular input, could
compete with the excitatory inputs from vestibular neurons on abducens motoneurons. The convergence of prepositus and medial vestibular inputs
on abducens neurons might summate to provide both peak acceleration and
jerk-related signals in response to translational acceleration (Fig.
8A). We assume that MVe input
across the midline is excitatory (Scudder and Fuchs
1992
) and that the PrH is inhibitory (Escudero et al.
1992
). The MVe input to the abducens nucleus is characterized
by a relatively flat gain in the signal that is phase-related to peak
head acceleration. The signal that represents the same cells'
responses to an orthogonal vector is phase related to the rate of
change of acceleration (jerk) and exhibits a gain increase with
stimulus frequency (Angelaki et al. 1993
). Conversely, our present findings suggest that Type II PrH neurons can provide a
signal to the contralateral abducens that is phase-related to jerk and
exhibits a falling gain as a function of stimulus frequency (Fig. 5).
The postsynaptic effect of these two inputs, converging an abducens
motoneuron (as depicted in Fig. 8A), would result in a
greater sensitivity to head acceleration at lower frequencies and an
increasing sensitivity to jerk as the stimulus frequency increases.
These combined characteristics are reflected in the gerbil tVOR (Fig.
3).
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Interpretation of the functional significance of the rotational
response of vestibular-related neurons requires certain underlying assumptions. We assume that the postsynaptic responses of cells receiving Type I inputs are excitatory, whereas Type II inputs from the
PrH produce inhibitory responses. Because the PrH projections to the
abducens nuclei are largely crossed (Belknap and McCrea 1988; McCrea 1988
; McCrea and Baker
1985
), we propose that those connections involve PrH Type II
cells the axon terminals of which converge with those of
contralaterally projecting MVe Type I neurons. By logical extension,
the PrH projection to the ipsilateral medial rectus division of the
oculomotor nucleus also would be carried by axons from PrH Type II
cells. Because the MVe and PrH are known to be reciprocally connected
bilaterally (McCrea 1988
), we propose that PrH Type I
neurons provide excitatory feedback to the vestibular nuclei,
specifically through contralateral projections to the MVe Type II
inhibitory interneurons that also receive inputs, via the vestibular
commissural connections, from contralateral MVe Type I cells.
The gerbil horizontal rotational VOR exhibits a frequency dependent
gain increase (Fig. 3). This is consistent with the response gain
increase found in PrH Type I neurons that likely converge and summate
with MVe crossed inputs to the abducens nucleus. The additional
proposed inhibitory input from the PrH Type II cells should have a
lesser effect on the rotational VOR because their gains are relatively
low and flat across the tested frequency range. The models are
predicated on circuitry that largely is based on anatomic findings. In
our previous work (Angelaki et al. 1993) and in the
current study, none of the recorded neurons was identified in terms of
their direct synaptic projections to the oculomotor nuclei. Therefore
the models serve to suggest potential connections that could be
examined in future studies. For the present, we can only draw
comparisons between the response properties of the various populations
of neurons and those of the VOR. Adding the anatomic evidence of the
connectivity within the VOR pathway, the most parsimonious arrangement
would be one in which the projection of the PrH to the abducens and the
oculomotor nuclei are those of Type II cells as depicted in Fig. 8,
A and B. Based on our present findings this is a
conceivable set of connections.
Comparison with other species
A comparison of unit data from several species (rat: Lannou
et al. 1984; cat: Blanks et al. 1977
;
Escudero et al. 1996
; Godaux and Cheron
1996
; Kitama et al. 1995
; Lopez-Barneo et
al. 1982
; and monkey: Cullen et al. 1993
;
McFarland and Fuchs 1992
) reveals similar findings with
regard to rotational gains and cell types. Although previous studies
focused on different stimuli and response dynamics, like others
(Lopez-Barneo et al. 1982
; McFarland and Fuchs
1992
), we observed vestibular-only and Type II vestibular cells
with ipsilateral eye-movement sensitivity. However, we noticed a higher
percentage of canal-otolith convergent cells than a previous study that
employed static head tilt as an otolith stimulus (92/223 vs. 2/13)
(Blanks et al. 1977
). Other studies (immobilized rat: Lannou et al. 1984
; and anesthetized cat: Blanks
et al. 1977
; Godaux and Cheron 1996
), in
agreement with this report, also showed an ~2:1 ratio of Type II to
Type I neurons encountered in the perihypoglossal region.
The horizontal translational VOR response in the gerbil was similar to
that reported in the rat (Hess and Dieringer 1990, 1991
). Gerbils normally possess a monocular temporal-nasal
optokinetic reflex (Israelian gerbils) (Sontheimer and Hoffmann
1987
). The lack of foveal vision in this and other rodent
species prevents tasks that can separate sensory from oculomotor
signals on individual units.
The rich and diverse nature of the neurons found in the vestibular-related brain stem could provide dynamically appropriate output responses through simple combinations of those neuronal response properties. Given subsets of neurons may dominate the region's impact on vestibular function for a common range of motion stimuli, but the responses of other neural groups could provide dynamic signals for performance outside of that range to maintain proper behavioral performance. The increasing level of complexity in the understanding of vestibular function necessitates higher resolution descriptions of individual neural groups in the vestibular pathway. This study provides evidence to indicate a manner in which a neural population could accomplish such dynamic modulation by simple signal convergence.
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ACKNOWLEDGMENTS |
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This work was supported in part by National Institute on Deafness and Other Communication Disorders Grant DC-00385, National Aeronautic and Space Administration Grant 5-6009, and National Research Council Associate Grant 9602390.
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FOOTNOTES |
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Address for reprint requests: A. A. Perachio, Dept. of Otolaryngology, University of Texas Medical Branch, 7.102 MRB, Galveston, TX 77555-1063.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 29 June 1999; accepted in final form 22 December 1999.
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REFERENCES |
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