Latencies of response of eye movement-related neurons in the region of the interstitial nucleus of Cajal to electrical stimulation of the vestibular nerve in alert cats

Summary Recent studies have shown that the interstitial nucleus of Cajal (INC) in the midbrain reticular formation is involved in the conversion of vertical semicircular canal signals into eye position during vertical vestibuloocular reflexes. Secondary vestibulo-ocular relay neurons related to the vertical canals, which constitute the majority of output neurons sending signals from the vestibular nuclei directly to the oculomotor nuclei, have been shown to project axon collaterals to the region within and near the INC. To understand how the INC is involved in the signal conversion, latencies of response of neurons in the INC region to electrical stimulaton of the vestibular nerve were examined in alert cats. The responses of 96 cells whose activity was clearly modulated by sinusoidal pitch rotation (at 0.31 Hz) were analyzed. These included 41 cells whose activity was closely correlated with vertical eye movement (38 burst-tonic and 3 tonic neurons), and 55 other cells (called pitch cells as previously). Twenty nine of the 96 cells (30%) were activated at disynaptic latencies following single shock stimulation of the contralateral vestibular nerve. Disynaptically activated cells were significantly more frequent for pitch cells than for eye movement-related cells (25/55 = 45% vs 4/41 = 10%; p < 0.001, Chi-square test). Conversely, cells that did not receive short-latency activation (< 6 ms) were more frequent among eye movement-related cells than pitch cells (26/41 = 63% vs 13/55 = 24%; p < 0.001, Chi-square test). Pitch cells showed significantly less phase lag (re head acceleration) than eye movement-related cells during sinusoidal pitch rotation (mean ± SD 124° ± 17° vs 138° ± 14°. p < 0.01, t-test). These results suggest that 1) cells in the INC region other than burst-tonic and tonic neurons mainly receive direct inputs from secondary vestibulo-ocular relay neurons, and that 2) vertical canal signals reach eye movement-related neurons mainly polysynaptically.     

Spatial properties of vertical eye movement-related neurons in the region of the interstitial nucleus of Cajal in awake cats

Summary 1. Maximal activation directions of vertical burst-tonic and tonic neurons in the region of the interstitial nucleus of Cajal (INC) were examined in alert cats during vertical vestibulo-ocular reflex induced by sinusoidal rotation (at 0.11 Hz±10 deg, or 0.31 Hz±5 deg) in a variety of vertical planes using a null point analysis. The results were compared with the angles of anatomical and functional planes of vertical canals reported by Blanks et al. (1972) and Robinson (1982), and with the angles of vertical eye muscles measured in this study and by Ezure and Graf (1984). 2. Maximal activation directions of 23 cells (21 burst-tonic and 2 tonic neurons) were determined from their responses during rotation in 4 or more different vertical planes. All cells showed sinusoidal gain curves and virtually constant phase values except near the null regions, suggesting that their responses were evoked primarily by canal inputs. Phase values of 5 cells near the null regions depended on the rotation plane, suggesting additional otolith inputs. We used a measurement error range of ±10 deg for calculating the maximal activation directions from the null regions of individual cells and the values of error ranges of null calculation. Of the 23, the maximal activation directions of 7 cells were outside the measurement error ranges of vertical eye muscle angles and within the ranges of vertical canal angles (class A), those of 5 cells were within the ranges of eye muscle angles and outside the ranges of vertical canal angles (class B), and those of the remaining 11 cells were in the overlapping ranges for both angles (class C). Even if only the cells in which 5 or more measurement points were taken to determine maximal activation directions (n = 15), the results were similar. During vertical rotation with the head orientation +60 deg off the pitch plane, dissociation of cell activity and vertical compensatory eye movement was observed in 5 cells in class A or C that had null angles near +45 deg. These results suggest that the cells in class A and B carried individual vertical canal and oculomotor signals, respectively, although it is difficult to tell for the majority of cells (class C) which signals they reflected. Some cells in class A and C were antidromically activated from the medial longitudinal fasciculus at the level of abducens nucleus, suggesting that the signals carried by these cells may be sent to the lower brainstem. 3. Most burst-tonic neurons did not respond to horizontal rotation; significant responses were obtained in only 3 of 10 cells tested for which the gain was only 14–17% of their maximal vertical gain. There was no clear difference in gain or phase values of the responses to vertical rotation, or in eye position sensitivity (during spontaneous saccades) between cells whose responses coincided with individual vertical canal angles and those matching the angles of vertical recti muscles. The values of phase lag (re head acceleration during pitch rotation) and eye position sensitivity of these cells are still smaller compared to those of extraocular motoneurons reported by Delgado-Garcia et al. (1986), although they were larger than those of secondary vestibulo-ocular neurons (Perlmutter et al. 1988). All these results suggest that the signals carried by burst-tonic and tonic neurons in the INC region are different from oculomotor signals. 4. Similar analysis was done for comparison for 19 other cells that did not show close correlation with spontaneous eye movement but whose activity was clearly modulated by pitch rotation (pitch cells). More than a half (10/19) had maximal activation directions outside the measurement error ranges of individual vertical canal angles, and many shifted towards roll. Horizontal rotation produced responses with higher gain than burst-tonic neurons, suggesting a difference in the spatial response properties of burst-tonic and tonic neurons on one hand and pitch cells on the other.     

Vertical eye movement-related type II neurons with downward on-directions in the vestibular nucleus in alert cats

The vestibular nuclei and the interstitial nucleus of Cajal (INC) have been regarded as key elements of the velocity-to-position integrator for vertical eye movements. This paper reports a class of type II vestibular neurons that receives input from the INC and carries vertical eye movement signals that appear to represent an intermediate stage of the integration process. Extracellular recordings were made from neurons in and near the vestibular nuclei in alert cats. We encountered 39 neurons that exhibited an intense burst of spikes for downward saccades and a position-related tonic activity during intersaccadic intervals (d-type II neurons). They had a very high saccadic sensitivity (4.3±2.7 spikes/deg, mean ± SD) as well as a high position sensitivity (3.2±1.6 (spikes/sec)/deg). Unlike the bursts of motoneurons, the bursts of these neurons declined gradually with an exponential-like time course and lasted well beyond the end of saccades. The mean time constant of the burst decay was 139±43 ms. The d-type II neurons were excited with disynaptic or trisynaptic latencies following stimulation of the contralateral vestibular nerve. The responses to vertical head rotations suggested inputs from the contralateral posterior canal. The d-type II neurons were excited with short latencies following stimulation of the ipsilateral INC, suggesting that they receive a direct excitatory input from vertical eye movement-related INC neurons with downward on-directions. The d-type II neurons were located in the rostral portion of the vestibular nuclei and the underlying reticular formation. These results suggest that d-type II neurons may be interposed between the burst-tonic neurons in the INC and pure tonic neurons in the vestibular nuclei and contribute to the oculomotor velocity-to-position integration.     

Activity of eye-movement-related neurons in the region of the interstitial nucleus of Cajal during sleep

Activity of vertical burst-tonic neurons in the region of the interstitial nucleus of Cajal (INC) in cats that showed a close correlation with spontaneous vertical eye movement during the waking state was compared to that during sleep. All the cells tested maintained high and regular discharge rates similar to those during the waking state when the eye was near the primary position. However, a significant correlation between tonic discharge rates and vertical eye position change seen during the waking state was lost during slow drifting eye movement during sleep, indicating that they are not involved in such eye movement. Upward (or downward) burst-tonic neurons showed bursts (or decreased activity) during upward rapid-eye movements (REMs) accompanied by failure of eye position holding with almost exponential decay during REM sleep. However, the increased (or decreased) activity was not maintained and quickly returned to near-previous discharge rates. Despite the fact that a significant positive correlation was seen between average discharge rates during vertical saccades and tonic rates after saccades for these neurons during the waking state, the same cells lost such a correlation during vertical REMs with eye position holding failure. The close correlation between presence or absence of tonic activity related to preceding bursts of burst-tonic neurons, on the one hand, and holding or failure of vertical eye position after vertical saccades or REMs, on the other, suggests that these neurons receive excitatory and inhibitory burst inputs, and also that they are involved in some aspect of vertical eye position generation, but that the INC region alone cannot convert the burst signals into eye position.     

Activity of eye movement-related neurons in and near the interstitial nucleus of Cajal during sinusoidal vertical linear acceleration and optokinetic stimuli

Summary 1. A total of 43 neurons that showed a close correlation with vertical eye movement with a burst-tonic or tonic type response during spontaneous saccades, were recorded within, and in the close vicinity of, the interstitial nucleus of Cajal (INC) in alert cats. Neuronal responses to sinusoidal vertical linear acceleration (0.2–0.85 Hz, amplitude 10.5 cm) and optokinetic stimuli (0.1–1.0 Hz, amplitude 10.5 cm), were examined. 2. All 43 eye movement-related neurons responded to sinusoidal vertical linear acceleration in the presence of a stationary visual pattern in correlation to robust eye movement responses with compensatory phase. Phase and gain values (re stimulus position) of response of individual cells were independent of the stimulus frequencies tested. Of these, 33 cells were examined during linear acceleration without visual input. Most cells (27/33) did not respond even when a weak linear vestibulo-ocular reflex was present (6/27). The remaining 6 cells (6/33) responded to linear acceleration. Their mean phase values advanced by 80 ° and gain dropped by 55% compared to the responses with visual inputs. 3. Twenty eight of the 43 cells were examined during vertical optokinetic stimuli. The activity of all 28 cells was modulated in correlation to eye movement responses. Response phase showed more lag, and gain decreased as stimulus frequencies increased, similar to optokinetic eye movement responses. 4. The close correlation between the activity of eye movement-related neurons in the INC region and robust eye movements during linear acceleration with visual inputs and optokinetic stimuli suggest that these neurons are involved in some aspect of vertical eye position generation during such stimuli.     

Vertical eye movement-related secondary vestibular neurons ascending in medial longitudinal fasciculus in cat I. Firing properties and projection pathways

1. The firing characteristics and projection patterns of secondary vestibular nucleus neurons involved in the vertical vestibuloocular pathways were investigated in alert cats. Single-unit recordings were made in the medial longitudinal fasciculus (MLF) near the trochlear nucleus from axons that were monosynaptically activated after electrical stimulation of the vestibular nerve. In a total of 253 identified secondary neurons, 225 discharged in relation to vertical eye movements; 189 of these increased their firing rate for downward eye movements and 36 for upward movements. The activity of the remaining 28 axons was not related to eye movements when the head was still. 2. Virtually all of the secondary neurons with downward on-direction displayed tonic activity that was primarily related to steady eye position during fixation (DPV neurons). The slope of the relationship between firing rate and vertical eye position ranged from 1.2 to 9.1 (spikes/s)/deg with a mean of 3.2 (spikes/s)/deg. The regularity of firing was quantified by calculating the coefficient of variation (CV) of interspike intervals. A comparison of the CV in the population units indicated that DPV neurons could be classified as either regular or irregular neurons. There was a tendency for regular neurons to have higher firing rates and higher correlation coefficients for the rate-position relationships than irregular neurons. 3. During pitch rotation in the light, all the DPV neurons tested increased their firing rate with upward head rotation. Both the phase and the amplitude of the response indicated that DPV neurons discharged not only in relation to eye position but also in relation to head velocity, suggesting that they received monosynaptic input from the posterior semicircular canal. The gain and phase lag of the response relative to head velocity were measured at 0.5 Hz. The range of the gain was 1.1-5.1 (spikes/s)/(deg/s), and that of the phase lag was 18.3-62.4 degrees. There was a tendency for irregular DPV neurons to have a larger gain and smaller phase lag than regular DPV neurons. 4. Ascending and descending projection pathways were determined for 147 DPV axons. Of these, 69 ascended in the contralateral MLF with respect to their soma (crossed-DPV axons), and 78 in the ipsilateral MLF (uncrossed-DPV axons), as revealed by their monosynaptic activation from the contralateral or ipsilateral vestibular nerve. Stimulation of the caudal MLF at the level of the obex evoked direct responses caused by antidromic activation of descending collaterals in approximately 70% (49/69) of the crossed-DPV axons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Saccade-related burst neurons with torsional and vertical on-directions in the interstitial nucleus of Cajal of the alert monkey

The interstitial nucleus of Cajal (iC) is known to be the neural integrator for vertical and torsional eye movements. Burst-tonic neurons are thought to be the neural substrate for this function. Until now, the iC has not been specifically considered to play a part in saccade generation. The aim of this study was to characterize saccade-related burst neurons in the iC during torsional and vertical eye movements. Saccade-related burst neurons were recorded in the iC of macaque monkeys during fast phases of torsional and vertical vestibular nystagmus, spontaneous and visually guided eye movements, and in light and darkness. Burst neurons in the iC (n=85) were found intermingled between burst-tonic and tonic neurons. They were not spontaneously active, showed no eye position sensitivity, and responded during saccades and quick phases of nystagmus with a burst of activity whose duration was closely correlated with saccade amplitude and hence saccade duration (correlation coefficients up to 0.9). Latency in the on-direction was, on average, 10.4 ms (range 5–23 ms); it decreased with different saccade directions and became negative in the off-direction. In a horizontal-vertical coordinate system, on-direction of the majority of neurons was either upward (n=52) or downward (n=33). There was no horizontal on-direction. Burst neurons of different vertical on-directions were found intermingled throughout the iC. In the vertical-torsional plane, on-direction always showed an ipsiversive torsional component, i.e., a clockwise (positive) torsion for neurons in the right iC and a counterclockwise (negative) torsional component when recorded in the left iC. The findings indicate that saccade-related burst neurons in the iC control coordinate axes for vertical and torsional quick eye rotations. As in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), burst neurons in the iC encode vertical saccades with an ipsitorsional direction with similar burst characteristics. It is suggested that iC burst neurons play a part in the local feedback loop of the reciprocal iC-riMLF projections.     

The interstitial nucleus of Cajal in the midbrain reticular formation and vertical eye movement.

Bilateral lesions of the midbrain reticular formation within, and in the close vicinity of, the interstitial nucleus of Cajal (INC) result in the severe impairment of the ability to hold eccentric vertical eye position after saccades, phase advance and decreased gain of the vestibulo-ocular reflex (VOR) induced by sinusoidal vertical rotation. In addition, the INC region of alert animals contains many burst-tonic and tonic neurons whose activity is closely correlated with vertical eye movement, not only during spontaneous saccades, but also during the VOR, smooth pursuit and optokinetic eye movements. Although their activity is closely related to these conjugate vertical eye movements, it is different from the oculomotor motor neuron activity. These results indicate that the INC region is involved in, and indispensable for, some aspects of eye position generation during vertical eye movement. Further comparison of INC neuron discharge with eye movements during two special conditions indicates that the INC region alone cannot produce eye position signals. First INC neuron discharge shows no response or an 80 degrees phase advance (close to the expected value if there is no integration) in the dark compared to the light during sinusoidal vertical linear acceleration in alert cats. Second, during rapid-eye-movement (REM) sleep, the discharge of INC neurons is no longer correlated with eye position. These results imply that the INC is not the entire velocity-to-position integrator, but that it has to work with other region(s) to perform the integration. A close functional linkage has been described between vertical-eye-movement-related neurons in the INC region and vestibulo-ocular relay neurons related to the vertical semicircular canals in the vestibular nuclei. It has been suggested that both are the major constituents of the common neural integrator circuits for vertical eye movements.     

Discharges of neurons in the dorsal paraflocculus of monkeys during eye movements and visual stimulation

Extracellular recordings were obtained from 319 input units and 304 Purkinje cells (P-cells) in the dorsal paraflocculus of alert monkeys trained to fixate a visual target. They changed discharge rates with either eye movement, eye position, or visual stimulus movement. Of the 319 input units, recorded in the granular layer or white matter, most were mossy fibers (MFs), but 90 (28%) showed characteristic cellular spikes. The latter units were probably granular cells (p-GC). Of the 319 input units, 163 (51%) showed bursts with saccades (burst units) and 62 (19%) showed a prelude on the average 124 ms prior to the onset of saccade (long-lead burst units). Sixty-five (20%) had tonic activity related to eye position and also showed bursts with saccades (burst-tonic units), and the remaining 29 (9%) showed only tonic activity (tonic units). MFs and p-GCs showed no significant differences in the proportion of each type of unit or in their response properties. The majority of burst units (63%) were pan directional, whereas all long-lead burst units had directional selectivity. The preferred directions of long-lead burst, burst tonic, and directionally selective burst units were found in all four quadrants. Position-related activity was found in 48% of the burst-tonic and tonic units to be linearly related to eye position and to show position threshold. The other units also had position thresholds but their activity was not monotonically related to fixation position. Six climbing fibers (CFs), 32 input units (including 13 p-GC), and 8 P-cells showed cyclic responses during sinusoidal movements of a visual pattern. One class of MF units (57%) responded only to the direction, whereas the others responded to both the direction and retinal-slip velocity. Both CF and P-cell units responded to sinusoidal retinal-slip velocity. Of 67 input units, 23 showed cyclic modulation in firing during sinusoidal eye movements in the horizontal plane. Nineteen were burst-tonic and four were tonic units. They also showed position sensitivity. The phase of the cyclic responses tended to lag behind the eye velocity during low-frequency trackings. Of 237 P-cells, 163 (68.8%) discharged with saccades (burst P-cells), 42 (17.7%) paused with saccades (pause P-cells), and 32 (13.5%) discharged with saccades in one direction and paused in the other (burst-pause P-cells). Position sensitivity was found in 38 P-cells; 12 were burst, 5 were pause, and 10 were burst-pause P-cells. Eleven did not respond with saccades.(ABSTRACT TRUNCATED AT 400 WORDS)     

Discharge patterns in nucleus prepositus hypoglossi and adjacent medial vestibular nucleus during horizontal eye movement in behaving macaques.

1. Monkeys were trained to perform a variety of horizontal eye tracking tasks designed to reveal possible eye movement and vestibular sensitivities of neurons in the medulla. To test eye movement sensitivity, we required stationary monkeys to track a small spot that moved horizontally. To test vestibular sensitivity, we rotated the monkeys about a vertical axis and required them to fixate a target rotating with them to suppress the vestibuloocular reflex (VOR). 2. All of the 100 units described in our study were recorded from regions of the medulla that were prominently labeled after injections of horseradish peroxidase into the abducens nucleus. These regions include the nucleus prepositus hypoglossi (NPH), the medial vestibular nucleus (MVN), and their common border (the "marginal zone"). We report here the activities of three different types of neurons recorded in these regions. 3. Two types responded only during eye movements per se. Their firing rates increased with eye position; 86% had ipsilateral "on" directions. Almost three quarters (73%) of these medullary neurons exhibited a burst-tonic discharge pattern that is qualitatively similar to that of abducens motoneurons. There were, however, quantitative differences in that these medullary burst-position neurons were less sensitive to eye position than were abducens motoneurons and often did not pause completely for saccades in the off direction. The burst of medullary burst position neurons preceded the saccade by an average of 7.6 +/- 1.7 (SD) ms and, on average, lasted the duration of the saccade. The number of spikes in the burst was well correlated with saccade size. The second type of eye movement neuron displayed either no discernible burst or an inconsistent one for on-direction saccades and will be referred to as medullary position neurons. Neither the burst-position nor the position neurons responded when the animals suppressed the VOR; hence, they displayed no vestibular sensitivity. 4. The third type of neuron was sensitive to both eye movement and vestibular stimulation. These neurons increased their firing rates during horizontal head rotation and smooth pursuit eye movements in the same direction; most (76%) preferred ipsilateral head and eye movements. Their firing rates were approximately in phase with eye velocity during sinusoidal smooth pursuit and with head velocity during VOR suppression; on average, their eye velocity sensitivity was 50% greater than their vestibular sensitivity. Sixty percent of these eye/head velocity cells were also sensitive to eye position. 5. The NPH/MVN region contains many neurons that could provide an eye position signal to abducens neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Discharge patterns of levator palpebrae superioris motoneurons during vertical lid and eye movements in the monkey.

1. We recorded single-unit activity in the caudal central nucleus (CCN) of the oculomotor complex in monkeys trained to make vertical saccadic, smooth-pursuit, and fixation eye movements. We confirmed that our recordings were from motoneurons innervating the upper lid, because small lesions placed at the sites of responsive units were recovered among neurons labeled by horseradish peroxidase (HRP) injections into the levator palpebrae superioris muscle. 2. For fixations above a threshold lid position, levator motoneurons discharged at a steady rate, which increased linearly with upward lid position. The average position sensitivity during fixation was 2.9 spikes/s per deg, and the average lid motoneuron was recruited into steady firing when the eye was looking 10 degrees down. 3. During upward saccades, levator motoneurons discharged a burst of spikes that began, on average, 7.3 ms before the lid movement if the saccade started from a straight-ahead position; the lead time decreased considerably as the initial eye and lid positions shifted downward. The firing rate usually reached its peak (130-280 spikes/s) at the very onset of the burst and declined gradually during the course of the saccade. The steady rate associated with the new fixation position was reached about halfway during the saccade. All units exhibited a pause in firing during the initial half of large downward saccades; during small saccades, the pause was inconspicuous or absent. 4. During vertical sinusoidal smooth pursuit, levator motoneurons exhibited a sinusoidal modulation in firing rate, which led eye position by an average of 23 degrees at 0.3 Hz. The average velocity sensitivity calculated from such data was 0.63 spikes/s per deg/s. 5. Although they exhibit a number of qualitative similarities, the discharge patterns of levator motoneurons and superior rectus motoneurons differ in several respects. First, during a blink, when the lid undergoes a large depression but the eye exhibits only a brief transient displacement, levator motoneurons cease firing completely, whereas superior rectus motoneurons continue to discharge. Second, for all types of coordinated lid and eye movements, levator motoneurons discharge at lower firing rates than do superior rectus motoneurons. Third, during saccades, levator motoneurons have less conspicuous and shorter-lasting bursts and pauses than do motoneurons involved in rotating the eye. 6. During upward gaze, the qualitative similarity of their burst-tonic discharge patterns suggests that levator and superior rectus motoneurons receive input signals that originate from a common source, but that the signals are processed differently to deal with the different loads facing these muscles.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of lesion of the interstitial nucleus of Cajal on vestibular nuclear neurons activated by vertical vestibular stimulation

Summary 1. Experiments were performed in cats anesthetized with nitrous oxide to study the effects of INC lesions on responses of vestibular nuclear neurons during sinusoidal rotations of the head in the vertical (pitch) plane. Responses of neurons in the INC region were recorded during pitch rotations at 0.15 Hz. A great majority of these neurons did not respond to static pitch tilts, and they seemed to respond either to anterior or to posterior semicircular canal inputs with a peak phase lag of 140 deg (re head acceleration). 2. Responses of vestibular nuclei neurons in intact cats were recorded during pitch rotations at the same frequency (0.15 Hz). Neurons that seemed to respond to vertical semicircular canal inputs showed peak phase lags of 90 deg relative to head acceleration, whereas neurons that responded to static pitch tilts showed peak phase shifts near 0 deg. These results indicate that responses of neurons in the INC region lag those of vestibular neurons by about 50 deg, suggesting that the former neurons possess a phase-lagging (i.e. integrated) vestibular signal. 3. Responses of vestibular neurons in cats that had received electrolytic lesions of bilateral INCs 1–2 weeks previously were recorded during pitch rotations at the same frequency (0.15 Hz). Neurons that presumably responded to vertical semicircular canal inputs showed a peak phase lag of 60 deg relative to head acceleration, a significant decrease of the phase lag compared to normal, whereas responses near 0 deg were unchanged. Gain values of individual cells also significantly dropped from 2.07 ± 0.67 spikes · s⁻¹/deg · s⁻²2 (mean ± SD; normal cats) to 1.27 ± 0.68 spikes · s⁻²/deg · s⁻² (INC lesioned cats) at 0.15 Hz. When responses of vestibular neurons were studied during pitch rotations in the range of 0.044–0.49 Hz in these cats, a large decrease of the phase lag was observed at lower frequencies, whereas the slopes of phase lag curves of vestibular neurons in intact cats were rather flat. 4. Procaine infusion into the bilateral INCs not only resulted in a decrease of 20–50 deg in the phase lag in responses of vestibular neurons that had lagged head acceleration by 90–140 deg before procaine infusion, but also dropped the gain of the response to rotation by an average of 31%, whereas responses of neurons that had showed phase shifts near 0 deg were not influenced consistently. Simultaneous recording of the vestibular neurons and the vertical vestibuloocular reflex (VOR) indicated that the phase advance and gain drop of vestibular neurons occurred earlier than those of the VOR. These results exclude the possibility that the change in dynamic response of vestibular neurons after procaine infusion is due to depression of general brain stem activity that may lead to the phase advance of the VOR, and suggest that the decrease of the phase lag and gain drop in responses of the vestibular neurons was caused by removal of the phase-lagging, feedback signal coming from the INC to the vestibular nuclei.     

Role of primate flocculus during rapid behavioral modification of vestibuloocular reflex. II. Mossy fiber firing patterns during horizontal head rotation and eye movement.

1. Extracellular recordings were obtained from 113 mossu fibers (MFs) in the flocculus of alert monkeys trained to perform a visual tracking task during sinusoidal, horizontal head rotation. The analysis of MF discharge patterns was designed to allow quantitative comparison of the discharge properties of flocculus MFs with brain stem cell populations from which the MFs might originate and with flocculus Purkinje cells (P-cells). Based on their firing patterns, MFs were divided into two classes. Vestibular MFs discharged in relation to head velocity and, in some cases, also in relation to eye movement. Eye movement MFs discharged only in relation to one or more components of eye movement. 2. Vestibular MFs were subdivided into three classes. Vestibular-only MFs (n = 15) displayed a modulation in firing rate during head rotation but exhibited no relationship to spontaneous eye movements. Vestibular-plus-saccade MFs (n = 14) displayed a modulation in firing rate during head rotation that quantitatively resembled the modulation in vestibular-only MFs. In addition, a pause in firing rate interrupted the vestibular modulation during saccades in one or more directions. Vestibular-plus-position MFs (n = 4) exhibited steady firing rates that were linearly related to horizontal eye position in the absence of vestibular stimulation. Sinusoidal head rotation evoked a modulation ofiring rate above and below the firing rate set by the eye position. 3. during sinusoidal head rotation, vestibular MF firing rate led head velocity by an average of 24 degrees. The amplitude of MF firing-rate modulation increased as a function of the frequency of head rotation and, hence, maximum head velocity. Since these characteristics are similar to those displayed by P-cells during suppression of the VOR, vestibular MFs probably transmit the head velocity component of P-cell firing rate to the flocculus. Based on evidence from other mammals and a quantitative comparison of population discharge characteristics, it is likely that vestibular MFs originate from the vestibular nerve and from cells in the medial vestibular nucleus. 4. Based on their discharge patterns, eye movement MFs were also subdivided into three classes. Burst MFs (n = 14) emitted a high-frequency burst of spikes prior to and during saccades in one or more direction, but were silent during steady fixation. Burst-tonic MFs (n = 53) emitted a burst of spikes prior to saccades in a preferred ("on") direction, ceased firing during saccades in the opposite ("off") direction, and exhibited steady firing rates that increased as steady gaze shifted in the on direction. Tonic MFs (n = 13) displayed steady firing rates that increased as the position of steady gaze shifted in the on direction, and either paused or exhibited step changes in firing rate during saccades. 5. During steady fixation, 64% of tonic and burst-tonic MFs were recruited into maintained firing within +/- 10 degrees of the primary direction of gaze...     

A neurophysiological study of prepositus hypoglossi neurons projecting to oculomotor and preoculomotor nuclei in the alert cat

The activity of 62 antidromically identified prepositus hypoglossi neurons was recorded in 10 alert cats during spontaneous, vestibular or visually induced eye movements. Neurons were antidromically activated from stimulating electrodes implanted in the ipsilateral medial longitudinal fasciculus (n = 24), the ipsilateral interstitial nucleus of Cajal (n = 6), the ipsilateral parabigeminal nucleus (n = 2), the contralateral superior colliculus (n = 6) and the contralateral cerebellar posterior peduncle (n = 24). Neurons were identified as eye-movement-related when their rate-position and/or rate-velocity plots showed correlation coefficients greater than or equal to 0.6. They were further classified as "position", "position-velocity" and "velocity-position" according to their relative eye position and velocity coefficients. However, they seemed to be distributed as a continuum in which a progressive decrease of eye velocity sensitivity was accompanied by a proportional increase in eye position sensitivity. "Position-velocity" neurons (n = 9) were mainly horizontal type II neurons projecting to the vicinity of the oculomotor complex; two of these neurons with vertical sensitivity were also activated from the interstitial nucleus of Cajal. Mean position and velocity sensitivity of these neurons were 5.2 spikes/s per degree and 0.62 spikes/s per degree per second, respectively. Pure "position" neurons (n = 7) also showed activation during ipsilateral eye fixations; their mean position gain was 7.3 spikes/s per degree and they projected to the ipsilateral oculomotor and Cajal nuclei, and to the contralateral superior colliculus. "Velocity-position" neurons (n = 18) were type I or II neurons with rather irregular tonic firing rates and a mean velocity gain of 0.75 spikes/s per degree per second. Type II "velocity-position" neurons projected mainly to the oculomotor area, while type I neurons projected preferentially to the cerebellum. A special type of "pause" neuron (n = 5), with very low firing rate and pausing mainly for contralateral saccades, was activated exclusively from the contralateral posterior peduncle. Many neurons with weak eye movement sensitivity (n = 22) were activated mainly (73%) from the cerebellum. It can be concluded that the prepositus hyperglossi nucleus distributes specific eye movement related signals to motor and premotor brainstem and cerebellar structures. The variability of interspike intervals of representative prepositus hypoglossi neurons of each class was compared to the discharge variability of identified abducens motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Behavior of neurons in the abducens nucleus of the alert cat--II. Internuclear neurons

The activity of 43 antidromically identified abducens internuclear neurons with conduction velocities ranging from 14 to 54 m/s was analyzed in alert cats during spontaneous and vestibular induced eye movements. The discharge rate of internuclear neurons significantly increased with successive adducting positions of the contralateral eye. Slopes of rate-position (k) relationships ranged from 3.1 to 17.9 spikes/deg (mean 12.01 +/- 3.1). Threshold ranged from -19 degrees to +3 degrees. Frequency saturation was never observed for any internuclear neuron within the oculomotor range. Although straight lines were selected to illustrate the rate-position relationships, exponential curves always provided the best statistical fit demonstrating that an enhancement in frequency potentiation (k) must accompany more eccentric fixations in the on direction. Internuclear neurons showed a low variability in firing rate (less than 3.0%) for fixations less than 1 s. Variability increased with both longer and repeated fixations of the same eye position. Discharge rates were found to depend upon both the direction of the preceding eye movement and the animal's level of alertness. Separate regression lines of rate-position relations following saccades in the on and off directions differed significantly in slope (100%), but not threshold. The observed static hysteresis in an identified non-motoneuron shows this property to be in a central neural circuit prior to the extraocular motoneuron. The slopes (k) of rate-position plots for all internuclear neurons decreased significantly (100%) when level of alertness changed from "alert" (1 +/- 0.2 saccades/s) to "drowsy" (0.5 +/- 0.2 saccades/s). Thresholds, however, were not significantly altered. Discharge rate of abducens internuclear neurons increased abruptly 10.4 +/- 2.5 ms preceding saccades in the on direction, and decreased 20.5 +/- 7.8 ms before saccades in the off direction. Internuclear neuronal activity was not affected by pure vertical saccades. During on direction saccades, firing frequency did not saturate, but increased with velocity in a linear fashion. Exponential functions often fit the data better due to the difference in slopes of rate-velocity plots for on vs off direction saccades. Slopes (rs) of rate-velocity regression lines during spontaneous saccades ranged from 0.99 to 4.10 spikes/s/deg/s (mean 2.16 +/- 0.93). During saccades in the off direction activity always decreased, but it seldom ceased. Rate-velocity regression lines measured during the fast phase of vestibular nystagmus (rsv = 2.09 +/- 0.88) showed no significant differences from rs slopes in 82% of the cases.(ABSTRACT TRUNCATED AT 400 WORDS)     

The interstitial nucleus of Cajal is involved in generating downward fast eye movement in alert cats.

We examined whether or not the interstitial nucleus of Cajal (INC) is involved in generating vertical fast eye movement. We used a gamma-aminobutyric acid (GABA) agonist (muscimol) to deactivate the INC cell bodies bilaterally in alert head-fixed cats. The INC was identified by recording vertical eye position-related burst-tonic neurons. Following muscimol infusion into the bilateral INC, the cats were unable to hold eccentric upward eye position after saccades, and the mean time constant of postsaccadic drift was 0.4 sec. In addition, downward saccades were virtually lost without clear impairment of horizontal saccades. Muscimol infusion into the Forel's field H resulted in loss of both upward and downward fast eye movement as reported previously. Bilateral electrolytic INC lesions produced results similar to those after muscimol infusion into the INC, suggesting that the cutting of passing fibers in the INC alone cannot explain the selective loss of downward fast eye movement. These results indicate that the INC itself is involved in generating downward fast eye movement. We propose that the loss of activity in possible downward burster-driving neurons in the INC can explain the selective loss of downward fast eye movement after bilateral INC lesions.     

Minimal synaptic delay in the saccadic output pathway of the superior colliculus studied in awake monkey

The synaptic organization of the saccade-related neuronal circuit between the superior colliculus (SC) and the brainstem saccade generator was examined in an awake monkey using a saccadic, midflight electrical-stimulation method. When microstimulation (50–100 A, single pulse) was applied to the SC during a saccade, a small, conjugate contraversive eye movement was evoked with latencies much shorter than those obtained by conventional stimulation. Our results may be explained by the tonic inhibition of premotor burst neurons (BNs) by omnipause neurons that ceases during saccades to allow BNs to burst. Thus, during saccades, signals originating from the SC can be transmitted to motoneurons and seen in the saccade trajectory. Based on this hypothesis, we estimated the number of synapses intervening between the SC and motoneurons by applying midflight stimulation to the SC, the BN area, and the abducens nucleus. Eye position signals were electronically differentiated to produce eye velocity to aid in detecting small changes. The mean latencies of the stimulus-evoked eye movements were: 7.9±1.0 ms (SD; ipsilateral eye) and 7.8±0.9 ms (SD; contralateral eye) for SC stimulation; 4.8±0.5 ms (SD; ipsilateral eye) and 5.1±0.7 ms (SD; contralateral eye) for BN stimulation; and 3.6±0.4 ms (SD; ipsilateral eye) and 5.2±0.8 ms (SD; contralateral eye) for abducens nucleus stimulation. The time difference between SC- and BN-evoked eye movements (about 3 ms) was consistent with a disynaptic connection from the SC to the premotor BNs.     

Neuron activity in monkey vestibular nuclei during vertical vestibular stimulation and eye movements

To elucidate how information is processed in the vestibuloocular reflex (VOR) pathways subserving vertical eye movements, extracellular single-unit recordings were obtained from the vestibular nuclei of alert monkeys trained to track a visual target with their eyes while undergoing sinusoidal pitch oscillations (0.2-1.0 Hz). Units with activity related to vertical vestibular stimulation and/or eye movements were classified as either vestibular units (n = 53), vestibular plus eye-position units (n = 30), pursuit units (n = 10), or miscellaneous units (n = 5), which had various combinations of head- and eye-movement sensitivities. Vestibular units discharged in relation to head rotation, but not to smooth eye movements. On average, these units fired approximately in phase with head velocity; however, a broad range of phase shifts was observed. The activities of 8% of the vestibular units were related to saccades. Vestibular plus eye-position units fired in relation to head velocity and eye position and, in addition, usually to eye velocity. Their discharge rates increased for eye and head movements in opposite directions. During combined head and eye movements, the modulation in unit activity was not significantly different from the sum of the modulations during each alone. For saccades, the unit firing rate either decreased to zero or was unaffected. Pursuit units discharged in relation to eye position, eye velocity, or both, but not to head movements alone. For saccades, unit activity usually either paused or was unaffected. The eye-movement-related activities of the vestibular plus eye-position and pursuit units were not significantly different. A quantitative comparison of their firing patterns suggests that vestibular, vestibular plus eye-position, and pursuit neurons in the vestibular nucleus could provide mossy fiber inputs to the flocculus. In addition, the vertical vestibular plus eye-position neurons have discharge patterns similar to those of fibers recorded rostrally in the medial longitudinal fasciculus. Therefore, our data support the view that vertical vestibular plus eye-position neurons are interneurons of the VOR.     

Dynamic properties of eye position coded neurons in the alert monkey during saccades

Summary Single units in the regions of the III, IV and VI nuclei were recorded together with EOG's for horizontal and vertical eye positions in alert macaques. The sequential analysis of several dynamic parameters of the activity patterns in correlation to the saccade velocity for saccades in the on-direction leads to the results that: 1. eye position coded neurons can clearly be separated into two main classes [early peak (EP) and late peak (LP)] by means of their activity patterns during saccades in the on-direction; 2. the maximum impulse rate of EP neurons shows a better correlation with saccade velocity than the difference between maximum and initial impulse rate while the opposite is valid for LP neurons. EP neurons are likely to be motoneurons which initiate saccadic eye movements whereas LP neurons are too slow for this task because they reach their maximum impulse rate after half the saccadic time. The dynamic properties of LP neurons have several features similar to those of primary stretch receptors during ramp-like stretches. The possible influence of fusimotor activity on the oculomotor system is discussed. The fact that the relationship between dynamic index and saccade velocity shows subgroups of data supports the assumption that the state of alertness changes instantaneously in untrained monkeys.Supported in part by the National Eye Institute, U.S. Public Health Service under grant EY-00592 to Dr. G. Westheimer and by the Deutsche Forschungsgemeinschaft.     

Characteristics and functional identification of saccadic inhibitory burst neurons in the alert monkey

1. With the use of single-unit recording, the reticular formation immediately caudal to the abducens nucleus was searched for saccadic burst neurons in alert, trained rhesus monkeys. We recorded 80 short- and long-lead burst neurons, investigated their connections, and quantitatively analyzed their discharge characteristics. 2. Like excitatory burst neurons located rostral to the abducens, these caudal burst neurons fire optimally for ipsilaterally directed saccades, fire less for vertical saccades, and fire minimally, if at all, for contralateral saccades. The direction associated with the maximum number of spikes was approximately along the horizontal axis (1 +/- 12 degrees (SD); n = 33). 3. The first spike of the burst led the saccade by 2-120 ms, depending on the unit. Neurons were divided into short lead (45%) and long lead (55%) using a burst-lead criterion of 15 ms. In the on-direction, the discharges of both types exhibited strong correlations between number of spikes in the burst and size of the horizontal saccade component; duration of the burst and duration of the saccade; and peak frequency of the burst and peak velocity of the saccade. These relations were looser for long-lead neurons than for short-lead neurons. 4. Horseradish peroxidase injected into the abducens nucleus retrogradely labeled cells in the contralateral reticular formation where burst neurons were recorded, showing that cells in this region make crossed monosynaptic connections. There was good agreement between the limits of this region, as determined physiologically and anatomically. 5. Microstimulation at the locus of recorded burst neurons elicited EMG potentials in the contralateral lateral rectus muscle of the appropriate sign and latency for a monosynaptic inhibitory projection to abducens motoneurons. Stimulation also elicited eye movements consistent with inhibition of the contralateral lateral rectus. 6. It is argued that these characteristics make it likely that the short-lead neurons are the source of the afference which generate the pause in contralateral abducens motoneuron firing during adducting saccades. These neurons are therefore analogous to the inhibitory burst neurons (IBNs) found in the cat. The characteristics of long-lead burst neurons, particularly their lead, make them less likely to subserve this function. These cells might be better suited to providing input to omnipause neurons or to the short-lead IBNs.