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Department of Neurobiology, Washington University School of Medicine, St. Louis, Missouri
Submitted 17 October 2005; accepted in final form 10 January 2006
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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). To achieve foveal image stability, these eye movements, known as the translational vestibulo-ocular reflex (TVOR), must scale with both target distance and eccentricity (Paige and Tomko 1991; Schwarz and Miles 1991; Schwarz et al. 1989). Specifically, the horizontal velocity of each eye, 
, during translation with velocity v along a direction forming an angle 
with the forward axis should depend on eye-to-target distance, d, and eye position, 
, as follows (Angelaki and Hess 2001)
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; Angelaki and McHenry 1999; Busettini et al. 1994; Gianna et al. 1997; Hess and Angelaki 2003; McHenry and Angelaki 2000; Paige and Tomko 1991; Schwarz and Miles 1991; Schwarz et al. 1989; Telford et al. 1997), but also along any heading direction (Angelaki and Hess 2001; Hess and Angelaki 2003). In monkeys, the TVOR does not use sensory or "higher level" estimates of target distance (Wei et al. 2003), nor does it depend on factors like spatial attention or an upcoming eye movement (Wei and Angelaki 2006). Rather, d and in Eq. 1 seem to be exclusively specified by the current static location of the eyes. These behavioral observations suggest that scaling by d and in Eq. 1 requires efference copies of vergence angle and eye position.
Where in the vestibulo-ocular reflex pathways this scaling occurs remains unknown. Premotor cells for the VOR are found in the vestibular (VN) and prepositus hypoglossi (PH) nuclei. Recent studies of VN neuron responses suggest that all three eye movement-sensitive cell types thought to provide the primary premotor drive for slow eye movements, i.e., position-vestibular-pause (PVP), eye-head (EH) and burst-tonic (BT) neurons, change their firing rates as a function of vergence angle during eccentric rotation (Chen-Huang and McCrea 1999a,b; McConville et al. 1996). However, these experiments typically used low-frequency motion in the presence of visual feedback and/or co-activation of the RVOR that makes evaluation of vergence angle effects on vestibular translational signals difficult to interpret. To gain further insight into how and where vestibular information is scaled by a neural estimate of target distance, these experiments have characterized PVP, EH, and BT neural responses during pure translational motion in complete darkness.
Using TVOR cancellation conditions, it was proposed recently that the translation signal flow within the VN and PH differs for neurons whose firing rate increases with ipsilaterally or contralaterally directed eye movements (eye-ipsi cells: type II PVP/i-EH; eye-contra cells: type I PVP/c-EH cells, respectively; Angelaki et al. 2001; Meng et al. 2005). These studies concluded that 1) approximately one-half of the type II PVP and i-EH neurons, but none of the type I PVP and BT cells, were modulated during TVOR cancellation; 2) PVP and EH neurons whose firing rates increased for ipsilaterally or contralaterally directed eye movements were characterized by distinct dynamic properties during TVOR cancellation. These results were interpreted to suggest that eye-contra neurons exhibit more motor-like properties than eye-ipsi cells during translation. In addition, differential projections of sensory canal and otolith signals onto eye-contra and eye-ipsi cells, respectively, were proposed to exist within a shared premotor circuitry to generate the VORs. The hypothesis regarding a differential signal flow for eye-ipsi and eye-contra cells would also predict that distinct differences should exist between type I and type II PVP, as well as between c-EH and i-EH neurons, in their dependence of firing rate modulation on vergence angle during translation. Because previous studies never compared the viewing distance dependence of eye-ipsi and eye-contra cells in darkness, a main goal of this study was to directly test for these predictions.
Finally, in addition to viewing distance, Eq. 1 also requires scaling with target eccentricity (i.e., dependence on eye position, ). Unlike the dependence on vergence angle, virtually no data currently exist about how these neurons change their firing rate modulation during translation as a function of target eccentricity, a dependence that is most apparent during fore-aft motion (i.e., when = 0 in Eq. 1). Thus a second goal of this study was to investigate the neural correlates of the scaling of vestibular signals by eye position, by characterizing firing rate modulation during fore-aft motion for targets at different horizontal eccentricities. We found distinct differences in premotor cell types, with BT and contralateral EH cells exhibiting the largest vergence and eye position dependences. Preliminary results of this work have been presented in abstract form (Meng and Angelaki 2005).
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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, 2001; Meng et al. 2005). Briefly, animals were instrumented with a delrin head-restraint ring and a recording platform, as well as dual eye coils on both eyes. Eye coil signals were calibrated daily during experiments, as explained in detail elsewhere (Klier et al. 2005). All surgical procedures were performed under sterile conditions in accordance to institutional and National Institutes of Health guidelines. Motion stimuli were generated using a vestibular turntable consisting of a linear sled on top of a yaw-axis rotator (Neurokinetics, Pittsburgh, PA). The yaw axis was used to study neurons during rotations in the horizontal plane. The translational stimulus profiles were generated using the linear sled that moved in an earth-horizontal plane. Visual targets for fixation and pursuit were generated using a laser/x-y mirror galvanometer system (General Scanning), which was secured on the wall of the room (world-fixed targets). The projection screen was placed at 20 and 80 cm away from the animal. If neural isolation was maintained, data were also collected with the screen placed at 12 and 32 cm. Stimulus presentation and data acquisition were controlled with custom-written scripts within the Spike2 software environment using the Cambridge Electronics Device (CED, model power 1401) data acquisition system. For each recording session, the voltage signals of the two eye-coil assemblies, the three-dimensional (3-D) linear accelerometer signals (mounted on fiberglass members that firmly attached the animal's head ring to the inner gimbal of the rotator), and velocity and position feedback signals from the rotator and/or linear sled were anti-alias filtered (200 Hz, 6-pole Bessel), digitized at a rate of 833.33 Hz (CED, model 1401, 16-bit resolution), and stored on a PC for off-line analysis.
Extracellular recordings were obtained using epoxy-coated, etched tungsten microelectrodes (2- to 4-M
impedance; FHC, Bowdoinham, ME). Neural activity was amplified, filtered (300 Hz to 6 kHz), and passed both to an audio amplifier and to a BAK Instruments dual time-amplitude window discriminator the output of which was used to trigger the event channel of the CED data acquisition system that stored the time of the spike at a 10-µs resolution. Recordings concentrated in the medial boarder of the medial vestibular (VN) and prepositus hypoglossi (PH) nuclei (e.g., Fig. 1 in Meng et al. 2005), areas that have been previously shown to contain eye movement-sensitive cells, many of which project directly to the abducens and oculomotor nuclei (Cullen and McCrea 1993; McCrea et al. 1987; Scudder and Fuchs 1992).
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; Meng et al. 2005). Because previous work has suggested a potential difference in the role of neurons with ipsilateral and contralateral eye movement sensitivity (referred to as eye-ipsi and eye-contra, respectively; Angelaki et al. 2001; Meng et al. 2005), data are presented separately for these two subgroups of PVP and EH cells. For this reason, the nomenclatures we use either refer to the cell's vestibular preference (e.g., type I/type II) or to its eye movement preference (e.g., eye-ipsi/eye-contra). Because no difference between BT cells was found, ipsi- and contra-BT neurons have been considered together in this presentation. The main experimental protocol consisted of high-frequency sinusoidal translational and rotational motions. First, using the linear sled, animals were translated laterally (4 Hz, with a peak acceleration of 0.25g corresponding to a displacement of ±0.4 cm). Second, animals were rotated (4 Hz, with a peak velocity of 18°/s) about an earth-vertical axis in the midsagittal plane, intersecting the line connecting the two auditory meatii (6–7 cm behind the eyes). The viewing distance dependence of the TVOR or RVOR was tested by requiring the animals to fixate central targets at distances of 12, 20, 32, or 80 cm in a softly illuminated room, as well as during interleaved periods in darkness.
If cell isolation was maintained, data were also collected during 4- (±0.25g) and/or 2-Hz (±0.33g) fore-aft oscillations, while fixating targets at different horizontal eccentricities at a viewing distance of 20 cm. Because this experimental protocol was delivered only to a subpopulation of recorded cells and because our penetrations were typically centered medially in the VN/PH, our sample for this analysis did not include type I PVP neurons.
For all motion stimuli (yaw rotation, lateral translation, and fore-aft translation), separate behavioral windows (<±1°) were used for the left and right eyes. Typically, the animal had to maintain fixation for 1 s on the target and then the fixation point was extinguished, and the monkey was required to maintain fixation at the memorized target for another 1 s in darkness (windows were increased to ±2° during this period). Animals were rewarded once after both fixation and motion in darkness intervals, as long as eye position stayed within the specified windows. This sequence of light/dark periods (e.g., Figs. 2 and 3) was delivered multiple times for each cell, allowing quantification of the amplitude of compensatory eye movements during both target fixation and in complete darkness. Despite large variations in the dependence of the VOR amplitude on viewing distance and eye position among animals (e.g., Angelaki and Hess 2001; McHenry and Angelaki 2000; Paige and Tomko 1991; Schwarz and Miles 1991; Telford et al. 1997), data were very consistent across different stimulus presentations on different experimental days within the same animal (Fig. 1).
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). Positive directions were leftward and downward. Saccades and fast phases of nystagmus were identified and removed through a semiautomated computer algorithm based on a higher derivative of eye velocity (Angelaki 1998). To analyze neural firing rate, for each spike, an occurrence time was logged. Instantaneous firing rate (IFR) was calculated as 1/interspike interval and assigned to the middle of the interval. For each recorded run, neural data were also "desaccaded" using a window that extended from 50 ms before to 100–200 ms after each saccade (Scudder and Fuchs 1992). The static eye position sensitivity of cells was evaluated by recording neural activity during fixation of targets with eccentricities extending ±20° horizontally and vertically. Fixation data and multiple linear regression analyses were used to estimate the eye position sensitivity of the neurons.
To estimate peak neural response modulation and phase during rotation and translation, desaccaded neural activity from multiple stimulus cycles was folded in time into a single cycle instantaneous frequency response for each stimulus condition and fitted with a sinusoidal function (Meng et al. 2005). Notice that only sections where the animal's behavior was within the specified behavioral windows were included in the folding. This analysis gave the peak firing rate of each cell during either rotation or translation, in units of spikes/s. Neural TVOR gains were expressed relative to the linear acceleration stimulus, in units of spike/s/G (with G = 9.81 m/s2). RVOR and pursuit gains were expressed relative to peak head or eye (respectively) velocity in units of spikes/s/°/s. Phase for the TVOR and RVOR responses was expressed as the difference (in °) between peak neural activity and peak linear or rotational head velocity. Positive stimulus directions were leftward for rotation, leftward for lateral translation, and forward for fore-aft motion.
In addition to quantifying peak firing rate amplitude and phase, we also computed the corresponding mean vergence angle, as well as right and left eye positions. Thus a direct correlation between firing rate modulation and vergence angle (target distance) or eye position (target eccentricity) was possible. Notice that many VN/PH cells were also sensitive to static eye position and/or vergence angle. Thus the mean steady-state firing rate often changed as a function of target distance and eccentricity. The goal of these analyses was to quantify the linear acceleration, stimulus-driven component of neural firing rate (i.e., the cell's peak-to-trough sinusoidal modulation), and not mean changes in firing rate.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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Figure 1, A and B, shows the dependence of each of the 4-Hz yaw RVOR and lateral motion TVOR on vergence angle, plotted separately (column-wise) for each of the three animals used in these experiments. In agreement with previous reports (Schwarz and Miles 1991; Telford et al. 1997), the vergence dependence of the TVOR is larger than that of the RVOR, with regression slopes of 1.0–2.1 and 0.1–0.2°/s/° of vergence for the TVOR and RVOR in darkness, respectively. The vergence slopes tended to be larger during fixation of a world-fixed target, particularly during the TVOR (Fig. 1A, open symbols and gray lines).
As expected from Eq. 1, eye velocity during the TVOR also exhibits a dependence on target eccentricity. This dependence is maximal during fore-aft motion (when = 0), as shown in Fig. 1C, which plots the amplitude and phase of the 4-Hz fore-aft TVOR as each of the three animals used in these experiments fixated (or maintained fixation in darkness) at targets of different horizontal eccentricities at a distance of 20 cm. Each data point in the plot corresponds to the eye velocity elicited during the 4-Hz motion protocols for each recorded cell, shown separately for periods during target fixation and in complete darkness (Fig. 1, target on and off, respectively). The fore-aft TVOR exhibits a V-shape amplitude dependence and a phase reversal for right versus left eye positions (see also Angelaki and Hess 2001; McHenry and Angelaki 2000; Seidman et al. 1999).
Neural activity
Based on neuronal firing patterns during static fixations, 0.5-Hz smooth pursuit, and 0.5-Hz RVOR cancellation tasks (i.e., during rotation while fixating a head-fixed target that moves with the animal), VN/PH neurons were first classified into one of the following four groups (Table 1) (Chubb et al. 1984; Cullen and McCrea 1993; Fuchs and Kimm 1975; Keller and Daniels 1975; Keller and Kamath 1975; King et al. 1976; McFarland and Fuchs 1992; Miles 1974; Scudder and Fuchs 1992; Tomlinson and Robinson 1984): 1) neurons (VO) that responded during vestibular stimulation without any sensitivity for eye position and smooth eye velocity; 2) neurons (PVP) that changed their firing rates during rotation and pursuit in a complementary fashion, such that they exhibited maximal firing rate modulation during stable gaze RVOR [PVP cells modulated either in phase with ipsilateral head velocity during yaw RVOR cancellation and contralaterally directed eye velocity during horizontal smooth pursuit (type I PVP) or in phase with contralateral head velocity during RVOR suppression and ipsilaterally directed eye velocity during smooth pursuit (type II PVP)]; 3) neurons (EH) that exhibited RVOR cancellation and pursuit responses in the same directions, such that the two signals cancelled or opposed each other during stable gaze RVOR [this group included cells with ipsilaterally directed eye and head velocity sensitivities (i-EH) as well as cells with contralaterally directed eye and head velocity sensitivities (c-EH)]; and 4) neurons (BT) that exhibited both static eye position and pursuit sensitivities, but did not modulate during RVOR cancellation.
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= 0 (Eq. 1), the effects of eye position were characterized during fore-aft motion. Dependence of firing rate on target distance
Typical examples of PVP and EH cell responses during the TVOR are shown in Figs. 2 and 3. Each of the four sets of plots show IFR, along with binocular eye position, eye velocity and the linear acceleration stimulus, at two viewing distances: a far target, located at 80 cm and a near target, placed 20 cm away from the animal. Data were collected for 4-Hz motion while the animal fixated a world-fixed target in a softly illuminated room (target on) and during interleaved periods of total darkness (target off).
Viewing distance and the associated vergence angle had distinct effects on different cell types. For example, the type I PVP neuron of Fig. 2A showed some increase in peak-to-peak firing rate modulation at large vergence angles, although the modulation magnitude was typically small, even for the nearest target (Fig. 1A). In contrast, the c-EH cell of Fig. 2B exhibited large increases in firing rate with vergence angle; It modulated little during viewing of a target at 80 cm (corresponding to a small, <2°, vergence angle), but increased modulation amplitude by more than threefold for a target at 20 cm (and a vergence angle of 
8°).
A different picture emerged when considering neurons with ipsilateral eye movement preference (i.e., type II PVP and i-EH cells), as shown in Fig. 3. The most consistent behavior was shown by type II PVP cells, all of which modulated similarly during far and near viewing with changes in peak-to-peak response modulation amplitude being small or negligible (Fig. 3A). On the other hand, ipsilateral EH cells showed mixed behavior. For example, the cell whose responses have been plotted in Fig. 3B behaved similarly as type II PVP cells. That is, cell modulation was large and relatively independent of viewing distance. Other i-EH cells, however, behaved more like c-EH cells, where modulation amplitude was small during far target viewing but increased substantially during near viewing.
The mean ± SD firing rate modulation and phase of all cells tested during 4-Hz translational and rotational motions at 20 and 80 cm have been summarized in Table 1. A few of these cells did not modulate during 4-Hz motion at either viewing distance, despite the fact that they all exhibited robust 0.5-Hz responses and were reliably classified as PVP, EH, or BT cells. Using only cells with clear modulation for at least one viewing distance (TVOR: 45 cells; RVOR: 41 cells), two different analysis methods were used to quantify the dependence of cell firing rates on vergence angle. The first analysis separated the components of cell modulation that depended on vergence angle from those that did not. This method, which used data from all viewing distances, computed how much the peak firing rate modulation increased per degree of vergence. The second method used data at two viewing distances only (20 and 80 cm) and computed percent increases in firing rate (similar to Chen-Huang and McCrea 1999a,b).
The first analysis method is shown with four typical examples from type I PVP, c-EH, type II PVP, and i-EH cells in Fig. 4, A–D, where peak neural firing rate modulation, quantified using a sinusoidal function fit (see METHODS), was plotted as a function of the corresponding mean vergence angle, separately for data during fixation, as well as in interleaved periods of complete darkness (open vs. filled symbols, respectively). The dependence of neural firing rate on vergence angle was quantified using linear regression, separately for target on and off motion cycles (Fig. 4, open/filled symbols and gray/black lines, respectively). For neurons whose responses were tested at more than two viewing distances, r2 values varied between 0.04 and 0.99, with averages as follows: BT cells, 0.87 ± 0.12 (for 2/5, P < 0.05); PVP cells, 0.66 ± 0.33 (1/6, P < 0.05); EH cells, 0.85 ± 0.31 (for 6/8, P < 0.05).
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Mean ± SD of the vergence slope and the vergence-independent component values during translation in darkness for all 45 cells are summarized for each cell group in Fig. 5A. Because the vergence-independent component of cell firing rate was larger for cells that modulated during 0.5-Hz TVOR cancellation, compared with those that did not [F(43,1) = 32.2, P < 0.001], data are shown separately for the two groups (gray vs. black bars; none of the type I and BT cells exhibited modulation during TVOR cancellation; see also Meng et al. 2005). The vergence-independent component correlated positively with cell response modulation amplitude during the 0.5-Hz TVOR cancellation task (R2 = 0.78, 0.79 for target on and off, P < 0.001).
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For a direct comparison with previous results (Chen-Huang and McCrea 1999a,b), we also computed percent response changes, estimated as the difference in peak firing rate modulation between the 80- and 20-cm viewing distances, divided by the cell's peak firing rate for the 20-cm distance. Data for each cell group, as well as the corresponding mean percent changes in eye velocity, are summarized in Fig. 5B. With one exception, the results of this percent change analysis for the TVOR were identical to those presented earlier using the vergence slope metric. Specifically, percent increases in BT, c-EH, and i-EH firing rates were indistinguishable from the corresponding increase in TVOR eye velocity (t-test, P > 0.05 for all). Thus both sets of analyses revealed that BT and c-EH cells, and to a lesser extent i-EH cells, exhibited the largest change with vergence angle. In contrast, very little changes were seen for type II PVP cells.
The one exception was the type I PVP cell group, which showed small vergence slope values (Fig. 5A, top) but large percent increases with vergence angle (Fig. 5B). These two results are consistent and due to the very small modulation of type I PVP cells during high-frequency translation (e.g., Figs. 2A and 4A; Table 1). Specifically, although peak firing rates for type I PVP cells increased little with vergence angle (in terms of the regression line slope in units of spikes/s/° of vergence), mean percent changes were as large as those for BT and c-EH cells and closely matched the percent changes in TVOR eye velocity (Fig. 5B). Thus, although too small to account for the large TVOR eye velocity vergence-dependent slope, type I PVP response amplitude changes were proportionally appropriate for the behavioral effects.
Despite these amplitude changes, viewing distance did not alter the high-frequency response phase during either rotation or translation [repeated-measures ANOVA: F(40,1) = 1.2, P > 0.05]. There were, however, differences in high-frequency TVOR response phase among the different cell types (Fig. 6A). Specifically, phase leads (relative to linear head velocity) for EH (both i-EH and c-EH) and type II PVP cells were similar to each other (ANOVA, P > 0.05), but larger than the phase of type I PVP neurons (Fig. 6A; Table 1). In contrast, the TVOR phase of type I PVP neurons was not different from the phase of BT cells [F(12,1) = 1.3, P > 0.05]. Notably, the neural response phase of type I PVP cells during the RVOR was similar with the phase of type II PVP, i-EH, and c-EH cells (P > 0.05; Fig. 6B), all of which differed from BT neurons. Thus unlike rotation, the high-frequency phase leads of type I PVP neurons during translation were as small as those of the BT cells.
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In addition to target distance, the other geometrical property of the TVOR is its dependence on target eccentricity (i.e., its dependence on eye position, , in Eq. 1). We next describe the neural response properties during fore-aft motion as a function of eye position as animals fixated or maintained fixation on memorized targets at different horizontal eccentricities. In particular, as expected from the sinusoidal term in Eq. 1, eye velocity of the TVOR exhibits a "V-shape" amplitude dependence on eye position (Fig. 1C, top). In addition, the phase of eye velocity modulation relative to the linear acceleration stimulus is shifted 180° for left versus right eye positions (Fig. 1C, bottom) (Angelaki and Hess 2001; McHenry and Angelaki 2000; Paige and Tomko 1991; Seidman et al. 1999). Representative responses from a c-EH cell and a type II PVP neuron during 4-Hz fore-aft translation while fixating a left, a center, and a right target are shown, along with superimposed fits of a sinusoidal function (see METHODS), in Fig. 7. Similar to eye velocity, the c-EH neuron responses changed phase relative to the head acceleration stimulus (Hacc, bottom traces) for targets to the left versus targets to the right (Fig. 7A, top and bottom). In contrast, for the type II PVP neuron, firing rate did not change as a function of target location (Fig. 7B).
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) and in darkness (target off: 
) are compared with horizontal eye velocity (shown with + and x for target on and off, respectively) in Fig. 8. Once again, eye-contra and eye-ipsi cells responded differently. In particular, responses of c-EH neurons exhibited an eye position-dependence similar to that of eye velocity (Fig. 8A). The most salient change was the 180° shift in neural response phase for right versus left eye positions, similarly as horizontal eye velocity (Fig. 8A, bottom). In contrast, no 180° shift in response phase was seen for cells with ipsilateral eye movement preference (Fig. 8, B and C). The dependence of response amplitude on eye position was more idiosyncratic.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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; Meng et al. 2005), provide a clearer picture as to the role of these cell types in the generation of the TVOR. Dependence on target distance
Using two different methods of analyses, based either on the slope with which neural firing rates increased as a function of vergence angle or on the percent change in firing rate for viewing at 20 and 80 cm, we found that c-EH and BT neurons were the cell types that changed the most as a function of viewing distance. The other extreme was type II PVP neurons, where very small increases in firing rate with vergence angle were observed. I-EH neurons were in-between, with most cells responding like type II PVP neurons, although a few showed large vergence-dependent changes. Finally, type I PVP neurons showed very small vergence-dependent slopes, yet when expressed as percent changes, type I PVP percent increases, like those of c-EH and BT neurons, were as large as those of TVOR eye velocity. This was because the peak-to-peak modulation of type I PVP neurons during high-frequency translation under near viewing conditions was small in comparison to those of other cell types. As a result, although in absolute numbers the vergence-dependent slopes of type I PVP neurons were small, the percent changes paralleled the vergence-dependent scaling of the eye velocity.
These results are in general agreement with those of Chen-Huang and McCrea (1999a),b and McConville et al. (1996) during eccentric rotation in the presence of visual feedback, with a single exception: we found that the vergence-dependent slopes of neural firing rates depended on neural response gain during horizontal pursuit but not static eye position sensitivity. In contrast, Chen-Huang and McCrea (1999b) reported a significant correlation between the increase in the presumed "translational" component of cell firing for near versus far viewing and the cell's static eye position sensitivity. This difference could be caused by differences in visual conditions, the linear acceleration stimulus (0.03–0.05g, compared with 0.25g in these studies), or the combined canal/otolith stimulation (eccentric rotation) of previous studies (analysis of translational responses during eccentric rotation assumes that RVOR/TVOR signals add linearly, a presumption that is still debatable; Anastasopoulos et al. 1996; Fuhry et al. 2002; Telford et al. 1998; Wei and Angelaki 2004). The significance of such correlations of the vergence dependence of TVOR neural modulation with either pursuit (this study) or static eye position (Chen-Huang and McCrea 1999a,b) sensitivity is nevertheless unclear.
It is important to point out that these results, where we report selective changes in cell firing rate modulation during the TVOR as a function of target distance (vergence angle), should not be interpreted as if VN/PH neurons explicitly carry vergence (as opposed to monocular) eye position signals. Although several recent studies have characterized the presence of such signals in premotor areas (Sylvestre et al. 2003; Zhou and King 1998), the present experiments did not test whether neural firing rates during static fixations correlate best with vergence or monocular signals. Whether and how much neural firing rate modulation during the TVOR scales with viewing distance is not necessarily related to whether neural firing rates correlate best with vergence or monocular eye position.
Dependence on target eccentricity
Very prominent differences between BT/c-EH neurons and type II PVP/i-EH cells were also observed in their target position dependence during high-frequency fore-aft motion. In particular, both BT and c-EH cells had responses that depended on target eccentricity as did the respective eye velocity, including a response phase reversal for left versus right eye positions and a small response modulation for straight-ahead fixations. In contrast, type II PVP and i-EH cells had firing rates that did not change much as a function of eye position. This was particularly noticeable when considering the relationship of neural response phase for left versus right ocular positions: unlike eye velocity, the neural response phase of type II PVP and i-EH cells did not reverse by 180° (Fig. 9). Other than some preliminary results during low-frequency translation in the presence of visual feedback (Angelaki et al. 2001), this is the first study to examine neural response properties as a function of target eccentricity during translation. As will be summarized next, these differences in response properties suggest distinct roles of the different premotor cell types in generating the TVOR versus the RVOR.
Role of different cell types for the generation of compensatory eye movements during translation
The easiest cell type to place within the premotor pathway for both the TVOR and the RVOR is the BT group of neurons, which exhibit motor-like responses during both rotations and translations. None of these cells changes its firing rate during either RVOR or TVOR cancellation. In addition, all BT neurons scale their firing rates as a function of viewing distance and eye position congruent with TVOR eye velocity. Thus activity of this cell type is appropriate to drive eye movements during both the TVOR and RVOR.
Contralateral EH neurons represent the cell group that is closest in properties during translation to the motor-like characteristics of BT cells. Only a very small percentage of c-EH cells modulates during low-frequency TVOR cancellation (Angelaki et al. 2001; Meng et al. 2005). Furthermore, their activity during high-frequency TVOR scales with both target distance and eccentricity, congruent with the respective dependence of eye velocity. However, despite these similarities with BT neurons, their response dynamics during rotation and translation are different (e.g., Fig. 6), suggesting different roles within the premotor circuitry for slow eye movements (Green et al. 2004).
Importantly, type I PVP neurons, the main interneuron in the RVOR pathways that has been shown to receive direct semicircular canal inputs (Scudder and Fuchs 1992), do not share a similar role for the TVOR. Not only do they not receive direct otolith afferent inputs (Angelaki et al. 2001; Meng et al. 2005), but they also modulate little during high-frequency translation, even under conditions of near viewing. Another difference between type I PVP and other premotor types is that their response phase during the TVOR tends to be similar to that of BT cells and smaller (i.e., of less lead) than those of other cell types (Fig. 6, see also Table 1). This is not the case for the RVOR where, like other cell types, type I PVP cells lead eye velocity more than BT cells (Fig. 6; Table 1). Preliminary observations suggest that these differences generalize to multiple motion frequencies (Green et al. 2004). These results suggest that type I PVP neurons have different roles in the processing of sensorimotor signals for the two reflexes. Unlike the RVOR, where they are known to have a direct sensory contribution, type I PVP neurons are likely on the motor side of the premotor processing for the TVOR. These results support a previous proposal that direct semicircular canal, but only processed otolith signals, reach type I PVP cells (Angelaki et al. 2001).
Finally, it is clear that eye-ipsi neurons, including both type II PVP and i-EH cells, carry signals that are inappropriate to directly drive motoneuron firing rates during translation. The lack of tuning according to Eq. 1, the large vergence-independent component in their firing rates during high-frequency translation (Fig. 5A), and the fact that most cells modulate during low-frequency TVOR cancellation in the absence of eye movements (Angelaki et al. 2001; Meng et al. 2005) suggest that these cells carry more sensory-like signals that are independent of target distance and eccentricity. It is possible that these cells represent the interneuron in the weak three-neuron arc of the TVOR (Uchino et al. 1997), although why such a signal would be directly relayed to the motoneurons remains unclear.
Central to our understanding of the sensorimotor processing in the TVOR is testing how the vergence and ocular position-dependent modulations arise in the firing rates of these neurons. Probably related to this property is the distinct response dynamics of different cell types and the way they are interconnected with each other (Angelaki et al. 2001; Green et al. 2004). Furthermore, because many of the EH cells might represent floccular-target neurons (Lisberger and Pavelko 1988; Lisberger et al. 1994; Partsalis et al. 1995a,b; Zhang et al. 1995a,b), the role of the flocculus/ventral paraflocculus (FL/VPF) in these properties cannot be excluded. FL/VPF Purkinje cells have been reported to change their firing rates at short latency in response to translation (Snyder and King 1996), and patients with FL/VPFL lesions have large deficits in the TVOR (Baloh et al. 1995; Crane et al. 2000). Given the strongly interconnected and distributed nature of these signals, not to mention the bilateral nature of the premotor circuitry (Galiana and Outerbridge 1984; Green 2000), the task of unmasking these computations remains challenging.
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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Address for reprint requests and other correspondence: D. Angelaki, Dept. of Anatomy and Neurobiology, Box 8108, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110 (E-mail: angelaki{at}pcg.wustl.edu)
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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) and in complete darkness (Target Off, 
). Solid black and gray lines show linear regressions.
