Spatial Alignment of Rotational and Static Tilt Responses of Vestibulospinal Neurons in the Cat

S. I. Perlmutter, Y. Iwamoto, J. F. Baker, and B. W. Peterson

Department of Physiology, Northwestern University School of Medicine, Chicago, Illinois 60611


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Perlmutter, S. I., Y. Iwamoto, J. F. Baker, and B. W. Peterson. Spatial Alignment of Rotational and Static Tilt Responses of Vestibulospinal Neurons in the Cat. J. Neurophysiol. 82: 855-862, 1999. The responses of vestibulospinal neurons to 0.5-Hz, whole-body rotations in three-dimensional space and static tilts of whole-body position were studied in decerebrate and alert cats. The neurons' spatial properties for earth-vertical rotations were characterized by maximum and minimum sensitivity vectors (Rmax and Rmin) in the cat's horizontal plane. The orientation of a neuron's Rmax was not consistently related to the orientation of its maximum sensitivity vector for static tilts (Tmax). The angular difference between Rmax and Tmax was widely distributed between 0° and 150°, and Rmax and Tmax were aligned (i.e., within 45° of each other) for only 44% (14/32) of the neurons. The alignment of Rmax and Tmax was not correlated with the neuron's sensitivity to earth-horizontal rotations, or to the orientation of Rmax in the horizontal plane. In addition, the extent to which a neuron exhibited spatiotemporal convergent (STC) behavior in response to vertical rotations was independent of the angular difference between Rmax and Tmax. This suggests that the high incidence of STC responses in our sample (56%) reflects not only canal-otolith convergence, but also the presence of static and dynamic otolith inputs with misaligned directionality. The responses of vestibulospinal neurons reflect a complex combination of static and dynamic vestibular inputs that may be required by postural reflexes that vary depending on head, trunk, and limb orientation, or on the frequency of stimulation.


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The properties of vestibuloocular and vestibulospinal reflexes reflect the combination of information from semicircular canal and otolith receptors (Angelaki and Hess 1996; Baker et al. 1985; Gresty et al. 1987; Guedry 1966; Sargent and Paige 1991; Schor and Miller 1981; Wilson et al. 1986). The convergence of these signals is apparent in the responses of vestibular nucleus neurons (Angelaki et al. 1993; Baker et al. 1984; Curthoys and Markham 1971; Endo et al. 1995; Kasper et al. 1988; Lannou et al. 1980; Tomlinson et al. 1996; Wilson et al. 1990), reticular neurons (Bolton et al. 1992; Fagerson and Barmack 1995), and spinal interneurons (Endo et al. 1994; Schor et al. 1986), whose properties are determined by the relative directional tuning and dynamics of canal and otolith inputs.

Previous studies have found varying degrees of spatial and temporal alignment of inputs to vestibular nucleus neurons. In response to on-axis rotations, neurons with spatially aligned vestibular inputs exhibit response gain that is cosine-tuned to stimulus orientation, a null response orientation, and response dynamics that are independent of stimulus direction (Angelaki 1991; Schor et al. 1985). For these neurons, a "maximal vertical response vector" defines the rotation plane and direction that produces the strongest response to earth-vertical rotations. Responses that do not exhibit these properties have been termed "spatiotemporal convergent" (STC) and were originally described for secondary neurons in the cat (Baker et al. 1984; Goldberg et al. 1983). We hypothesized that STC behavior is generated by inputs from canal and otolith afferents that have different response dynamics and dissimilar preferred orientations. Kasper et al. (1988), Wilson et al. (1990), and Endo et al. (1995) found fewer neurons with STC responses in similar preparations. Most neurons had a maximal vertical response vector whose orientation was independent of rotation frequency. Many cells were classified as receiving otolith plus canal input based on their frequency responses. For these neurons, the stability of the response vector orientation across frequency suggested that a given neuron received canal and otolith inputs with the same directionality.

For central neurons with otolith inputs alone, previous studies also differ concerning the extent to which afferent inputs with different dynamics have the same directional preference. In cats with all canals plugged, Schor et al. (1985) found that the orientation preferences of neurons for angular rotations in vertical planes did not change for rotation frequencies between 0.01 and 2 Hz. In contrast, many neurons in the rat exhibited STC behavior in response to linear accelerations in the horizontal plane (Bush et al. 1993).

The present study further examines the relative spatial tuning of afferent inputs to vestibulospinal neurons by comparing their spatial properties to two types of natural stimuli: static tilts, which activate otolith receptors alone, and 0.5-Hz angular rotations, which activate canal and otolith afferents. The results will show that more than half of the neurons exhibit different directional preferences for inputs signaling static changes of head position and inputs generating dynamic responses to angular rotations.


    METHODS
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Data were collected in experiments described in detail in Perlmutter et al. (1998) and summarized briefly here. All procedures conformed to the Principles of Laboratory Animal Care (NIH publication No. 85-23, revised 1985) and were approved by the Northwestern University Animal Care and Use Committee. All preparatory surgery was performed with the animals under 1% halothane anesthesia.

Vestibulospinal neurons that responded both to maintained changes in head position and to 0.5-Hz rotations in vertical planes were selected for analysis. Data were obtained from two preparations. In seven precollicularly decerebrated and one intact, awake cats, neural activity was recorded extracellularly in the vestibular nucleus. Labyrinth electrodes were implanted unilaterally in the bulla tympanica for stimulation of vestibular afferents. Expoxylite-insulated, tungsten electrodes were advanced through a craniotomy opened over the cerebellum to regions where VIIIth nerve-evoked field potentials were recorded. Neurons were identified as vestibulospinal neurons by antidromic activation (cathodal pulses of 100 µs, threshold <= 500 µA) from metal electrodes implanted in the descending vestibulospinal tracts (in C1 for decerebrate animals; in the medial longitudinal fasciculus near the obex for the alert animal). In five other decerebrate cats, vestibulospinal neurons were recorded intra-axonally in the C1 ventral funiculus with micropipettes filled with KCl solution. The dorsal surface of the cord was exposed with a laminectomy of the C1 vertebra and resection of the dura mater. The animals were paralyzed with pancuronium bromide and artificially ventilated, and a bilateral pneumothorax was performed. Neurons were identified as secondary vestibular neurons by monosynaptic responses to stimuli delivered to labyrinth electrodes implanted in the bullae tympanica.

The responses of all neurons to sinusoidal, whole-body rotations at 0.5 Hz in the earth-horizontal and 2-11 (median, 8; 27/32 >=  6) earth-vertical planes were recorded. The animal's head was fixed to the rotation apparatus and pitched 28° nose down from stereotaxic coordinates to bring the vertical canals to a near vertical position (Blanks et al. 1972). The cat was placed on a turntable that could be positioned at any angle (i.e., orientation) about the earth-vertical axis, so that rotation about the earth-horizontal axis could deliver a stimulus in any vertical plane relative to the cat's head. In our coordinate system, vertical rotation with the cat in the 0° orientation produced a pitch stimulus, the 90° orientation produced a roll stimulus, the 45° orientation produced a stimulus in a plane near that of the left anterior-right posterior semicircular canal pair, and the 135° orientation produced a stimulus in a plane near that of the left posterior-right anterior canal pair. Rotations of 10° peak-to-peak amplitude were applied during extracellular recordings and 5° during intra-axonal recordings. Histograms of neural activity for a cycle of rotation were compiled from 40-80 s of rotation for each rotation plane and fitted with a 0.5-Hz sine wave using a least-squares error algorithm (Fig. 2Aa) (Schor et al. 1985). Response gain and phase were determined from the peak of the sine fit, and expressed relative to turntable position. Type I and type II responses were defined in the usual way, as activation during ipsilateral and contralateral (relative to the location of the neuron's soma) yaw or ear down rotation, respectively (Duensing and Schaefer 1958). Cell bodies were localized to the left or right vestibular nucleus by the recording side for neurons recorded extracellularly, and by the labyrinth that monosynaptically activated the cell for neurons recorded intra-axonally.

The neurons' responses to vertical rotations in different planes were modeled as having two-dimensional spatiotemporal sensitivity (Angelaki 1991; Bush et al. 1993). We implemented Angelaki's analysis of responses in multiple stimulation planes using the MATLAB (Math Works, Natick, MA) computational package (Angelaki et al. 1992). Gain and phase as a function of vertical rotation plane (orientation) were simultaneously fit with a simplex algorithm for minimizing least-squares error. The procedure specifies the neuron's maximal (Rmax) and minimal (Rmin) sensitivity vectors in the earth-horizontal plane, which define the axis and direction of rotation that produce maximal and minimal responses, respectively, for earth-vertical rotations. Of the two vectors perpendicular to Rmax, Rmin was defined as the axis of rotation that elicited a response with a phase that led by 90° the phase of the maximal response. Rmax and Rmin are shown as the semi-major and semi-minor axes of a response ellipse in the cat's horizontal plane.

The ratio of the magnitudes of Rmin to Rmax, termed the neuron's tuning ratio, was used as a quantitative measure of the extent of STC behavior exhibited by each neuron. We used Angelaki et al.'s (1993) criterion that neurons with tuning ratios >0.1 exhibit STC behavior, although this value is arbitrary.

For some neurons, frequency responses were also characterized in or near the plane that produced the cell's strongest response to vertical rotations. Activity was recorded in response to single sinusoidal or sum-of-sinusoids (Baker et al. 1985) stimuli with frequencies from 0.01 to 2 Hz.

Neurons that received input from canal afferents were identified using the response-phase criterion of Wilson, Schor, and colleagues, based on response dynamics across a range of stimulus frequencies (Bolton et al. 1992; Endo et al. 1994, 1995; Kasper et al. 1988; Wilson et al. 1990). Neurons that exhibited a phase lead exceeding 55° for 0.5-Hz rotations in the neuron's maximal response plane were classified as receiving canal input.

Static tilt, a maintained change of the cat's head position relative to gravity, was used as a pure otolith stimulus. The animal was rotated slowly in an earth-vertical plane until the head was pitched up or down by 10-45°, and held in position until the firing rate was judged to have remained constant for at least 20 s (Fig. 1Aa). Activity was recorded at several different tilt angles, both nose up and nose down, in each vertical plane. For each neuron, static tilts were delivered in two to four different vertical planes.



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Fig. 1. Responses to static tilts. A: data from a neuron in the left vestibular nucleus, recorded extracellularly in a decerebrate animal. Aa: firing rate (bottom traces) during tilts of whole-body position (top traces) in 2 vertical planes (indicated by cartoons to the right). Ab: plot of gain vs. tilt plane (orientation); solid curve is least-squares error fit. Negative gains correspond to peak firing for nose down and left ear down tilts when the cat was in the 0 and 90° orientation, respectively. Circled data points show gain for tilts in Aa. Ac: Tmax shows direction and plane of tilt, by the right-hand rule, that produces the maximal tilt response for this neuron. B: orientation of Tmax vectors in the horizontal plane, normalized to a length of one, for all 32 neurons. Vectors are shown as if the neurons' somas were in the left vestibular nucleus; thus neurons activated by ipsilateral ear down roll (i.e., left or right ear down for left or right vestibular nucleus neurons, respectively) have vectors in the top half of the figure. LED, left ear down tilt; RED, right ear down tilt; NU, nose up tilt; ND nose down tilt.

Steady-state responses to static tilts were analyzed as position detectors containing no temporal information. For each tilt plane, mean steady-state firing rate was calculated for each tested angle of head position, and tilt gain was taken as the slope of the least-squares fit of mean steady-state firing rate versus tilt angle. Gain was plotted as a function of stimulus orientation, and fit with a least-squares sine wave. A vector defining the plane and direction of static tilt that maximally excited the cell (Tmax) was determined from the values of the fitted sine function for tilts in the pitch and roll planes.

Response vectors were plotted in the cat's horizontal plane using a right-hand coordinate system to indicate the associated plane and direction of rotation or tilt. The spatial alignment of a neuron's responses to angular rotations and static tilts was quantified as the absolute value of the smallest angular difference (i.e., <= 180°) in the horizontal plane between Rmax and Tmax.

At the conclusion of each experiment, the locations of stimulating electrodes in the vestibulospinal tracts and some extracellular recording sites in the vestibular nucleus were marked electrolytically (20-30 µA for at least 20 s). The animals were anesthetized with an overdose of pentobarbital sodium and perfused with 10% Formalin or 4% paraformaldehyde. Stimulating and recording positions were verified using standard histological techniques.


    RESULTS
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Orientation of rotational and tilt responses

In our studies in alert and decerebrate cats (Iwamoto et al. 1996; Perlmutter et al. 1998), 65 vestibulospinal neurons were tested for sensitivity to changes in steady-state head position relative to gravity. The activity of 46 neurons (71%) was modulated by the static tilts, and we characterized the spatial tuning of the responses for 32 of these neurons, 23 recorded extracellularly and 9 recorded intra-axonally. Twenty-five of the neurons (16 of those recorded extracellularly and all those recorded intra-axonally) were judged to be secondary vestibular neurons based on monosynaptic activation following electrical stimulation of one labyrinth (see Perlmutter et al. 1998 for description of latency criterion). Responses were similar for neurons recorded extra- or intracellularly, in decerebrate or awake animals, and with or without monosynaptic input from vestibular afferents, and the data were combined.

The responses of a secondary vestibulospinal neuron, recorded in the left vestibular nucleus of a decerebrate cat, to static tilts in different earth-vertical planes are shown in Fig. 1Aa. Response gain was well fit as a sinusoidal function of stimulus orientation (Fig. 1Ab). Tmax indicated a maximal tilt response to nose down tilts in a plane near that of the right anterior canal (Fig. 1Ac; cf. response vectors of canal afferents in Fig. 2B). Tmax vectors for all 32 vestibulospinal neurons, normalized to a length of one, are shown in Fig. 1B. All vectors are shown as if the neuron's soma was in the left vestibular nucleus (i.e., vectors for neurons in the right nucleus were reflected about the roll coordinate axis). Tmax vectors were widely distributed, except that only one neuron had a Tmax near the axis of the ipsilateral posterior canal.



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Fig. 2. Responses to 0.5-Hz earth-vertical rotations. A: data from a neuron in the right vestibular nucleus, recorded intra-axonally in a decerebrate animal. Aa: histograms of neural activity for rotations in 4 planes (indicated by cartoons to the right); solid lines are least-squares fit sine wave. Ab: plots of gain and phase vs. rotation plane (orientation). Solid curves are best fits obtained with a simplex algorithm for minimizing least-squares error (Angelaki et al. 1992). Response phases were relative to peak nose up or right ear down excursion, indicated by dotted vertical lines on histograms in Aa. Circled data points show gain and phase for rotations in Aa. Ac: response ellipse for this neuron. Lines along the semi-major and semi-minor axes show Rmax and Rmin, respectively. Rmax and Rmin give the direction and plane of rotation, by the right-hand rule, that produce the neuron's maximal and minimal, respectively, response to earth-vertical rotations. B: orientation of Rmax vectors in the horizontal plane, normalized to a length of one and shown as if the neurons' somas were in the left vestibular nucleus, for all 32 neurons. Arrows show orientation of response vectors for canal afferents. Inset: shows Rmin (normalized to a length of 1) for neurons with tuning ratios >0.1. LED, left ear down roll; RED, right ear down roll; NU, nose up pitch; ND nose down pitch; lac, left anterior canal; lpc, left posterior canal; rac, right anterior canal; rpc, right posterior canal.

All 32 vestibulospinal neurons that were studied during static tilts also had clear responses to 0.5-Hz rotations in earth-vertical planes. Fifteen neurons were modulated only by vertical rotations, and 17 neurons were responsive to both vertical and horizontal rotations. Eighteen of 32 neurons (56%) had tuning ratios >0.1 for rotational stimuli, indicating STC behavior (44% had tuning ratios >0.2). The responses of one of these neurons, recorded intra-axonally, are shown in Fig. 2Aa. This secondary neuron, located in the right vestibular nucleus, had no null response plane and response phase varied with the orientation of the applied stimulus (Fig. 2Ab). The cell had a tuning ratio of 0.32 and a Rmax near right ear down roll (Fig. 2Ac). Rmax for all 32 vestibulospinal neurons, normalized to a length of one and shown as if the neurons' somas were in the left vestibular nucleus, are shown in Fig. 2B. Rmax vectors were grouped around the axes of the canals (arrows) or shifted toward roll, but none were near the pitch axis. Most neurons (24) were of the same response type when tested with rotations and tilts; that is, neurons with type I and type II responses to vertical rotations were usually activated by ipsilateral and contralateral ear down tilts, respectively.

There was no consistent relation between the orientation of Rmax and Tmax for individual neurons. The angular difference in the horizontal plane between a neuron's two maximum sensitivity vectors varied widely, from 1 to 150° (Fig. 3A). For descriptive purposes, we considered vectors that were within 45° of each other to be aligned. With the use of this criterion, Rmax and Tmax were aligned for 14 of 32 (44%) neurons. There was also no consistent relation between the orientations of Rmin (Fig. 2B, inset) and Tmax.



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Fig. 3. Alignment of Rmax and Tmax. A: histogram of absolute values of the angular difference in the horizontal plane between Rmax and Tmax for all neurons. Open and filled bars show neurons that did, and did not, respond to yaw, respectively. Neurons with yaw gain greater than maximal vertical gain indicated with asterisks (1 per bar). B: angular difference between Rmax and Tmax as a function of the neuron's tuning ratio. Open and filled circles indicate neurons that did, and did not, respond to yaw, respectively.

The variability in the spatial alignment of rotational and tilt responses could not be accounted for by other response properties of the neurons (ANOVA, P > 0.05). First, the proximity of Rmax to Tmax was not related to the degree of STC behavior exhibited in the neuron's response to 0.5-Hz rotations (Fig. 3B). Neurons with small or large tuning ratios could have rotational and tilt vectors that were either close or far apart. The normalized response ellipses and static tilt vectors for four different vestibulospinal neurons are shown in Fig. 4. The neuron in Fig. 4A had a tuning ratio of 0.03. Rotational response gain was well described as a cosine function of stimulus orientation with maximum sensitivity for nose down stimuli in a plane close to that of the ipsilateral anterior canal. Rotation in the perpendicular vertical plane elicited very little modulation of activity. Response phase was fairly constant for all orientations, ranging from 65 to 96° in advance of head position. The neuron's tilt response was also maximal in a plane near that of the ipsilateral anterior canal, and Rmax and Tmax were <1° apart. In contrast, the neuron in Fig. 4B, which had a tuning ratio <0.01, was maximally activated by nose up rotations in a plane near that of the ipsilateral posterior canal and by nose down static tilts about the pitch axis (Rmax and Tmax 128° apart). The neurons in Fig. 4, C and D, exhibited STC responses to vertical rotations (tuning ratios were both 0.34). Phase varied from near 0° to near 90° as a function of orientation, and the neurons did not have null response planes. Rmax and Tmax were 8° apart in Fig. 4C, both near the ipsilateral ear down roll axis. In contrast, the neuron in Fig. 4D responded maximally to rotations about the contralateral ear down roll axis and to static tilts about an axis 62° away, near the contralateral anterior canal plane.



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Fig. 4. Response ellipses and Tmax for four neurons indicate different relations between a cell's tuning ratio and the alignment of Rmax and Tmax. Rmax and Rmin (for neurons with tuning ratios >0.1) are shown as plain lines along the semi-major and semi-minor axes, respectively, of the response ellipse. Tmax are shown as lines with arrowheads. Rmax and Tmax normalized to a length of 1. All vectors are shown as if the neurons' somas were in the left vestibular nucleus. Two neurons were recorded intra-axonally (A and D), and 2 were recorded extracellularly (B and C), all in decerebrate cats. A: neuron with tuning ratio of 0.03; Rmax and Tmax overlap. B: neuron with tuning ratio <0.01; orientation of Rmax within the response ellipse (collapsed to a line) indicated. C and D: 2 neurons with tuning ratios of 0.34.

Second, the relation between Rmax and Tmax was not correlated with the neurons' sensitivity to earth-horizontal rotations. Neurons with no significant response to yaw, including all four neurons shown in Fig. 4, had a wide range of angular differences between Rmax and Tmax (shaded histogram, Fig. 3A). This was also true for neurons with significant horizontal canal input (open histogram, Fig. 3A), whether the response gain for yaw was greater than (asterisks, Fig. 3A) or less than the maximum vertical gain.

Finally, the spatial alignment of Rmax and Tmax was independent of the orientation of Rmax in the horizontal plane. There was no predisposition for neurons with type I responses, with type II responses, with Rmax near a canal axis, or with Rmax shifted toward one of the roll axes, to have maximal rotational and tilt vectors that were either aligned or unaligned.

Vestibular inputs

Sensitivity to static tilts indicated that all 32 neurons received inputs from otolith afferents. A definitive test for canal input was not performed. Nonetheless, we believe that most neurons also received inputs from canal afferents, based on response phase for 0.5-Hz rotations and on response dynamics measured for several neurons.

For most neurons, response phase was near velocity for rotations about axes near Rmax. Twenty-nine of 32 neurons (91%) had response phase >= 55° (mean phase lead, 76 ± 13°); these neurons were classified as receiving canal input based on the criterion of Wilson and Schor (see METHODS). Eight of these neurons were studied using rotations at multiple stimulus frequencies (0.01-2 Hz) about an axis within 45° of Rmax. These cells exhibited frequency responses that were characteristic of inputs from canal and otolith afferents (Kasper et al. 1988). Gain was relatively flat at frequencies below ~0.1 Hz and increased more than threefold from 0.1 to 1.0 Hz. Phase was near velocity in the midfrequency range and often became more advanced as frequency increased. Rmax and Tmax were >45° apart for 16/29 neurons with responses that suggested inputs from canal plus otolith afferents.

Three neurons classified as receiving only otolith input had response phases of 16, 46, and 53° for rotations about an axis near Rmax. The frequency response of one of these neurons was studied; it exhibited behavior characteristic of otolith input alone. Phase was near position at low and middle frequencies and became more lagged as frequency increased above 0.5 Hz. Gain was significant at 0.01 Hz and increased less than threefold between 0.1 and 1.0 Hz. Rmax and Tmax were >45° apart for two of three neurons that appeared to receive only otolith input.


    DISCUSSION
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Otolith contributions to neuronal responses

A larger percentage of neurons (56% using the criterion of Rmin/Rmax > 0.1) exhibited STC responses to rotational stimuli than in previous studies (Baker et al. 1984; Endo et al. 1995; Fukushima et al. 1990; Graf et al. 1993; Iwamoto et al. 1996; Kasper et al. 1988; Perlmutter et al. 1998; Wilson et al. 1990). Two factors probably account for this difference. First, the analysis method used in the current paper (Angelaki 1991) provides a more sensitive test of STC behavior (Bush et al. 1993). Empirical tests of STC behavior have varied, although there is a generally accepted theoretical description (Schor and Angelaki 1992). Second, neurons were selected by responses suggesting inputs from both canal and otolith afferents. Most previous studies also included neurons with inputs from only canal or only otolith afferents, which are less likely to exhibit STC behavior.

The spatial orientation of otolith responses for vestibular nucleus neurons has been studied previously in the cat with dynamic stimuli. Response vectors in the horizontal plane were oriented near the axes of the vertical canals or roll, with few neurons responding maximally in the pitch plane (Daunton and Melvill Jones 1982; Endo et al. 1995; Kasper et al. 1988; Schor et al. 1984, 1985; Wilson et al. 1990).

The distribution of Tmax in the present study was somewhat different. Tilt vectors were widely distributed, and some neurons had maximal responses for tilts in pitch. We did not see a difference between the distributions of Tmax orientations for neurons with and without sensitivity to horizontal rotations, as described for linear accelerations in the rat (Angelaki et al. 1993). However, many neurons had similar response gains for horizontal and vertical rotations, which was not reported for the rat.

Neurons with Tmax near pitch may represent a population not sampled in the earlier cat studies. Alternatively, these responses may be dependent on the type of stimulus applied. Angular displacements elicit responses with both static and dynamic components. The tilts used in the present study reveal static otolith inputs in isolation. Vestibular nucleus neurons with Tmax near the pitch axis could have dynamic otolith responses with a different orientation. Comparison of our results with those of Wilson and Schor suggests that some vestibular neurons receive static and dynamic otolith inputs with different spatial orientations. This possibility is discussed further in the next section.

It should be noted that Chan et al. (1985) reported vestibular neurons with spatial preferences near pitch in response to slow, constant-velocity, off-vertical axis rotations. Their constant-velocity stimulus may have revealed static otolith responses in much the same way as our static tilts.

Alignment of Rmax and Tmax

We found wide variation in the degree of alignment of static tilt and rotational response vectors for individual vestibulospinal neurons. Rmax and Tmax were >45° apart in the horizontal plane for 18 of 32 cells. For 0.5-Hz rotations, we expect Rmax to be strongly influenced by canal inputs (Tomko et al. 1981; although otolith afferents also respond, Fernandez and Goldberg 1976). This suggests that canal and static otolith inputs had similar orientations for less than half of the neurons.

Such widespread misalignment of static and dynamic vestibular inputs was not expected from previous findings obtained using purely rotational stimuli. The number of neurons exhibiting STC behavior or frequency-dependent response vector orientation in the vestibular nucleus (Baker et al. 1984; Endo et al. 1995; Iwamoto et al. 1996; Kasper et al. 1988; Perlmutter et al. 1998; Wilson et al. 1990), the reticular formation (Bolton et al. 1992; Fagerson and Barmack 1995; Yates et al. 1993), the fastigial nucleus (Siebold et al. 1997), or the spinal cord (Schor et al. 1986) has been relatively low. In addition, Angelaki et al. (1993) reported that vestibular neurons with vertical canal and otolith inputs had responses to linear accelerations and vertical rotations that suggested the "synergistic" activation of canal and otolith inputs to individual neurons.

A likely explanation for the large proportion of central neurons with dissimilar Rmax and Tmax is the convergence of static and dynamic otolith inputs with different directionality. Three lines of evidence support this proposal.

First, the activation of otolith afferents alone can generate STC behavior in central neurons. STC behavior has been reported in response to pure linear accelerations for vestibular nucleus neurons (Angelaki et al. 1993; Bush et al. 1993), and to sinusoidal rotations for nucleus reticularis gigantocellularis neurons that had no canal inputs (Fagerson and Barmack 1995). The spatial and temporal properties of individual otolith afferents are diverse (Fernandez and Goldberg 1976), and the combination of signals from regular and irregular otolith afferents with different polarization vectors appears to be sufficient to generate STC behavior (Angelaki 1993).

Second, the extent of STC behavior exhibited during 0.5-Hz rotations was not correlated with the spatial alignment of Tmax and Rmax. This was initially surprising, because these vectors reflect otolith and, to a large extent, canal input, respectively. The usual explanation for STC behavior in response to angular stimuli is canal and otolith inputs that are not spatially aligned. However, the spatial sensitivities of a neuron's static otolith and dynamic responses appear to be independent.

Third, three neurons exhibited a response phase for rotation about an axis near Rmax that suggested inputs from otolith, but not canal, afferents (Kasper et al. 1988; Wilson et al. 1990). For these neurons it is likely that Rmax represented the spatial sensitivity of a dynamic otolith response. Rmax and Tmax were >45° apart for two of three of these neurons.

Functional implications

Postural control requires complex input-output transformations that depend on the relative orientation of the head, trunk, limbs, and gravity (Nashner and Wolfson 1974). Static vestibular inputs can modulate or gate reflex responses to dynamic stimuli (Baker et al. 1987). The variable relative orientation of Tmax and Rmax exhibited by our neurons may reflect this modulation.

Neurons with different static and dynamic properties also may contribute to the generation of different compensatory movements in response to different frequencies of vestibular stimulation. A well-known frequency-dependent dichotomy of behavior exists for the vestibuloocular reflex. The eye movements that compensate for linear head accelerations and changes in head orientation with respect to gravity differ, yet these stimuli elicit ambiguous activation of otolith receptors. It has been suggested that appropriate responses are achieved by central, frequency-selective, otolith-ocular pathways (Baarsma and Collewijn 1975; Mayne 1974; Paige and Tomko 1991; Tomlinson et al. 1996), although central processing based on canal-otolith interactions has also been proposed (Angelaki et al. 1999; Merfeld and Young 1995). Static tilts and low-frequency accelerations might activate pathways that are organized to produce eye movements that oppose changes in head position with respect to gravity. High-frequency stimuli might activate vestibuloocular pathways that compensate for translational head movements.

Similar mechanisms may exist for vestibulospinal reflexes. For example, the vestibulocollic reflex acts to stabilize head position relative to gravity. Because of the large inertia of the head, this can be achieved by responding to a low-pass-filtered transformation of vestibular input (Mayne 1974). Evidence for such low-pass filtering in vestibulospinal pathways is found in the sluggishness of the rabbit's postural adjustment to changes in the orientation of the apparent gravitational vertical due to applied centrifugal forces (Brindley 1965). On the other hand, the vestibulocollic reflex can compensate for disturbances of head position at much higher frequencies (Goldberg and Peterson 1986; Wilson and Melvill Jones 1979). There is also some evidence that vestibulo-limb reflexes are frequency dependent (Soechting et al. 1977), although these findings have been somewhat controversial (Schor and Miller 1981; Wilson et al. 1986). Vestibulospinal neurons with different Tmax and Rmax are consistent with frequency-selective pathways that include overlapping populations of vestibular nucleus neurons.

Our data suggest that the convergence of canal and otolith signals onto vestibulospinal neurons generates diverse combinations of static and dynamic spatial properties. This convergence may enable reflex pathways to compensate for a wide range of vestibular stimuli. For many neurons, static and dynamic inputs are aligned and act synergistically in response to postural disturbances, as suggested previously (Angelaki et al. 1993; Kasper et al. 1988). Other neurons may be involved in more complex processing that depends on the context or temporal properties of vestibular input.


    ACKNOWLEDGMENTS

We are grateful to L. Barke for technical assistance.

This study was supported by National Institutes of Health Grants NS-22490, NS-17489, and DC-01559.

Present address of Y. Iwamoto: Dept. of Physiology, Institute for Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305, Japan.


    FOOTNOTES

Present address and address for reprint requests: S. I. Perlmutter, Dept. of Physiology and Biophysics, University of Washington, Box 357290, Seattle, WA 98195.

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 14 December 1998; accepted in final form 3 May 1999.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

0022-3077/99 $5.00 Copyright © 1999 The American Physiological Society