Vestibular nerve activity in the alert monkey during vestibular and optokinetic nystagmus

Summary Activity of vestibular nerve fibers and eye movements were recorded in the alert monkey during natural stimulation. The animal was rotated about a vertical axis in the dark with velocity trapezoids (vestibular), or a striped cylinder was rotated around the stationary monkey (optokinetic), or these stimuli were combined.After velocity steps in the dark, neuronal activity declined with a dominant time constant of 5–6 s. The time constant of nystagmus recorded simultaneously was always longer, on average 23 s. Vestibular nerve activity was not influenced by optokinetic patterns or additional visual stimuli during combined visualvestibular stimulation. Thus, in contrast to vestibular nuclei neurons, vestibular nerve activity in the alert monkey is only determined by head acceleration and cannot be related to the nystagmus response or visual stimuli.Supported by a grant from the Swiss National Foundation for Scientific Research 3.343-2.78     

The velocity response of vestibular nucleus neurons during vestibular,visual, and combined angular acceleration

Summary In alert Rhesus monkeys neuronal activity in the vestibular nuclei was measured during horizontal angular acceleration in darkness, acceleration of an optokinetic stimulus, and combined visual-vestibular stimulation. The working ranges for visual input velocity and acceleration extend up to 60 °/s and 5 °/s². The corresponding working range for vestibular input acceleration is wider and time-dependent. During combined stimulation, that is acceleration of the monkey in the light, a linear relation between neuronal activity and velocity could be established for all neurons. Type I vestibular plus eye movement neurons displayed the greatest sensitivity and had a small linear range of operation. Other vestibular neurons were less sensitive but had a larger range of linear response to different values of acceleration. Accelerating the animal and visual surround, simultaneously but in opposite directions, results in neuronal activity proportional to relative velocity over a limited range.Supported by a grant from the Swiss National Foundation for Scientific Research 3.672-0.77     

Carbachol effects on hippocampal neurons in vitro: dependence on the rate of rise of carbachol tissue concentration

Summary Extracellular activity from vestibular nuclei neurons and vertical eye movements were recorded in the alert cat during sinusoidal optokinetic stimulation in the vertical plane at frequencies varying from 0.0125 Hz to 0.75 Hz. Among a population of 96 vestibular units located in and around Deiters' nucleus, 73 neurons (76%) displayed a firing rate modulation which followed the input at the standard parameters of visual stimulation (0.05 Hz; 10.1 deg/s or 9.1 cm/s peak to peak velocity). Two different patterns of modulation were found. In 42 cells (57%) an increase in the firing rate was observed during motion of the visual scene in the downward direction, while 31 neurons (43%) showed the opposite behavior, with an enhanced firing rate during upward movement. The phase of the neuronal responses was close (± 45°) to the velocity peaks (+90°: downward and -90°: upward) of visual scene motion for 65 among the 73 neurons. Mean values of phase was-6.1 ± 19.5° (SD) and -3.2 ± 15.5° (SD) with respect to the +90° and -90° velocity peaks, respectively. In the frequency range 0.0125–0.75 Hz, the phase of the neuronal responses remained almost stable, with only a slight lag which reaches -22° at the 0.25 Hz visual stimulation. The firing rate modulation was found to be predominant at low frequencies (0.0125 Hz–0.25 Hz), with three distinct peaks of modulation occurring either at 0.025 Hz, 0.10 Hz or 0.25 Hz, depending on the recorded cells. Above 0.5 Hz, the cell modulation was very poorly developed or even absent. A gain attenuation was observed in all units, which was more important in cells showing a peak of modulation at 0.025 Hz as compared with the others (-20.7 dB vs -9.6 dB, respectively, in the 0.025 Hz–0.25 Hz decade). The gain of the optokinetic reflex (OKR) progressively decreased from mean values of 0.78 ± 0.15 to 0.05 ± 0.06 in the 0.025 Hz–0.5 Hz frequency range. A close correlation was observed between the OKR slow phase velocity and the modulation of the neuronal responses in the two cell populations with maximal modulations at 0.10 Hz or 0.25 Hz. No correlations were noticed in the third population characterized by a peak of modulation at 0.025 Hz. In all units, the phase of eye movement velocity and of neuronal responses were both related to the velocity of the visual surround motion. These correlations were also found when varying the amplitude of the visual stimulation at a fixed frequency. Saturation was observed in the unit responses at velocities above 68.5°/s. When considering both the gain attenuation in the frequency range and the correlation between firing rate modulation and OKR slow phase velocity, two rather different cell populations can be distinguished: one with neurons peaking at 0.025 Hz (strong gain attenuation; no correlation with OKR velocity) and one with neurons peaking at 0.10 Hz or 0.25 Hz (slight gain attenuation; correlation with OKR velocity). This study points to the influence of visual motion cues on vestibular nuclei unit activity in the low-frequency range. A velocity coding of visual — surround motion in the vertical plane is performed by vestibular neurons. Our results in the alert cat suggest that both retinal (retinal slip) and extraretinal (proprioceptive afferences from eye muscles, efference copy) inputs can be involved in this visually induced modulation of vestibular nuclei neurons.     

Visual-vestibular interaction in the flocculus of the alert monkey

Summary The activity of Purkinje cells (P-cells) was recorded in the flocculus of alert Rhesus monkeys under different conditions of visual-vestibular stimulation. Stimulus conditions were vestibular, optokinetic, combined and conflicting. About 10–20% of all P-cells were activated in their simple spike activity during conflicting stimulation to the recording side (type I) and gave no response or much less during vestibular stimulation. About half of these P-cells were also activated during optokinetic stimulation to the recording side at velocities above 40–60 deg/s. Simple and complex spike activity behaved in a reciprocal way with overlapping but not identical working ranges. Simple spike modulation was unidirectional, complex spike activity always bidirectional. Modulation of simple spike activity cannot be related to one single parameter of the sensory input or the oculomotor output. The hypothesis is put forward that the vestibular nuclei and the flocculus behave in a complementary fashion in processing visual-vestibular information, the flocculus being specialized for high velocity optokinetic nystagmus and suppression of vestibular nystagmus.Supported by a grant from the Swiss National Foundation for Scientific Research 3.343-2.78     

Purkinje cell activity in the primate flocculus during optokinetic stimulation,smooth pursuit eye movements and VOR-suppression

Summary Purkinje cell (PC), activity in the flocculus of trained monkeys was recorded during: 1) Vestibular stimulation in darkness. 2) Suppression of the vestibulo-ocular reflex (VOR-supp) by fixation of a small light spot stationary with respect to the monkey. 3) Visual-vestibular conflict (i.e. the visual surround moves together with the monkey during vestibular stimulation), which leads to attenuation or suppression of vestibular nystagmus. 4) Smooth pursuit eye movements. 5) Optokinetic nystagmus (OKN). 6) Suppression of nystagmus during optokinetic stimulation (OKN-supp) by fixation of a small light spot; whereby stimulus velocity corresponds then to image slip velocity.Results were obtained from PCs, which were activated with VOR-supp during rotation to the ipsilateral side. The same PCs were also modulated during smooth pursuit and visual-vestibular conflict. No tonic modulation during constant velocity OKN occurred with slow-phase nystagmus velocities below 40–60 deg/s. Tonic responses were only seen at higher nystagmus velocities. Transient activity changes appeared at the beginning and end of optokinetic stimulation. PCs were not modulated by image slip velocity during OKN-supp.The results show that in primates the same population of floccular PCs is involved in different mechanisms of visual-vestibular interaction and that smooth pursuit and certain components of OKN slow-phase velocity share the same neural pathway. It is argued that the activity of these neurons can neither be related strictly to gaze, eye or image slip velocity; instead, their activity pattern can be best interpreted by assuming a modulation, which is complementary to that of central vestibular neurons of the vestibular nuclei, in the control of slow eye movements.Supported by Swiss National Foundation for Scientific Research 3.343-2.78, and Deutsche Forschungsgemeinschaft, SFB 200, A2     

Velocity storage in the vestibulo-ocular reflex arc (VOR)

Summary Vestibular and optokinetic nystagmus (OKN) of monkeys were induced by platform and visual surround rotation. Vision prolonged per-rotatory nystagmus and cancelled or reduced post-rotatory nystagmus recorded in darkness. Presumably, activity stored during OKN summed with activity arising in the semicircular canals. The limit of summation was about 120 °/s, the level of saturation of optokinetic after-nystagmus (OKAN). OKN and vestibular nystagmus, induced in the same or in opposite directions diminished or enhanced post-rotatory nystagmus up to 120 °/s. We postulate that a common storage mechanism is used for producing vestibular nystagmus, OKN, and OKAN. Evidence for this is the similar time course of vestibular nystagmus and OKAN and their summation. In addition, stored activity is lost in a similar way by viewing a stationary surround during either OKAN or vestibular nystagmus (fixation suppression).These responses were modelled using direct pathways and a non-ideal integrator coupled to the visual and peripheral vestibular systems. The direct pathways are responsible for rapid changes in eye velocity while the integrator stores activity and mediates slower changes. The integrator stabilizes eye velocity during whole field rotation and extends the time over which the vestibulo-ocular reflex can compensate for head movement.     

Purkinje cell activity in the flocculus of vestibular neurectomized and normal monkeys during optokinetic nystagmus (OKN) and smooth pursuit eye movements

Summary 1. Single unit activity was recorded in the primate flocculus after the vestibular nerves were cut (bilateral vestibular neurectomy) during optokinetic nystagmus (OKN), smooth pursuit eye movements (SP) and whole field visual stimulation with gaze fixed on a stationary target light (OKN-suppression). Following vestibular neurectomy monkeys had no vestibular responses and no optokinetic after-nystagmus (OKAN) in the horizontal plane. However, OKN slow phases still reached steady state velocities of up to 100 deg/s. 2. After neurectomy, simple spike (SS) activity of Purkinje cells (P-cells) was modulated in relation to eye velocity, regardless of whether eye velocity was induced by a small target light moving in darkness (SP) or by a moving visual surround (OKN). In over 90% of the P-cells firing rate increased with eye velocity to the ipsilateral side and decreased with velocities to the contralateral side. Modulation in firing rate increased monotonically with increasing eye velocity. The strength of modulation was similar during SP and OKN for the same eye velocity. 3. The change in firing rate of P-cells in response to a sudden change in optokinetic stimulus velocity contained a component related to eye velocity and a component related to eye acceleration. Only a few P-cells were also modulated with image slip velocity during OKN-suppression. 4. The modulation of P-cells during SP and OKN was compared in normal and vestibular neurectomized monkeys. The sensitivity of floccular P-cells to eye velocity during SP was 1.14 imp·s^–1/deg·s^–1 in normal monkey and 1.28 imp·s^–1/deg·s^–1 after neurectomy. The similarity of eye velocity sensitivities demonstrates that neurectomy does not change the characteristics of floccular P-cell modulation during SP. In contrast, during OKN modulation of P-cells is quite different in normal and neurectomized monkey. In normal monkey, P-cells are modulated during steady state OKN for eye velocities above 40–60 deg/s only. This threshold velocity corresponds approximately to the maximal initial OKAN velocity (i.e. OKAN saturation velocity). After neurectomy, the threshold velocity is 0 deg/s and P-cells are modulated during steady state OKN also over ranges of eye velocities that do not cause a response in normal monkey. Sensitivities of P-cells to eye velocity during OKN for eye velocities above the threshold velocity are 1.0 imp·s^–1/deg·s^–1 in neurectomized monkey and 1.43 imp·s^–1/deg·s^–1 in normal monkey. 5. The hypothesis has been put forward that OKN slow phase velocity in normal monkey has two dynamically different components, a fast and a slow component. The results strongly suggest that the two components depend on different neuronal populations. Firing rate of floccular P-cells is modulated in relation to the fast component only. The results furthermore support the idea that it is the smooth pursuit system which may generate the fast component in the OKN slow phase velocity response.Supported by Swiss National Foundation for Scientific Research (Nr. 3.718-0.80 and 3.593-0.84)     

The effect of muscimol micro-injections into the fastigial nucleus on the optokinetic response and the vestibulo-ocular reflex in the alert monkey

Eye movements of four macaque monkeys were investigated after unilateral micro-injections of the GABA agonist muscimol (1 g in 1 l NaCl) into the caudal fastigial nucleus, i.e. the fastigial oculomotor region. Spontaneous eye movements in the dark and in the light were tested, as well as those evoked by vestibular stimulation in the dark (sinusoidal: 0.1–0.2 Hz, ±40–100 deg/s, velocity trapezoid acceleration 40 deg/s², constant velocity 120 deg/s), optokinetic stimulation (sinusoidal: 0.1–0.2 Hz, ±40–100 deg/s, constant velocity 60–100 deg/s), and visual-vestibular conflict stimulation. With these stimuli, smooth pursuit mechanisms (fast build-up of optokinetic slow phase velocity), the vestibulo-ocular reflex (VOR) and the velocity storage mechanism were investigated. Muscimol injections consistently led to specific eye movement changes which were maximal 30–60 min after the injection and lasted 4–6 h. The fast initial rise of OKN slow phase velocity to the contralateral side decreased by 45% (range 24%–82%) of its pre-injection value, while it was virtually unaltered on the ipsilateral side (average decrease of 1%, range from a decrease of 20% to an increase of 32%). For conflict ramp stimulation, the suppression of vestibular nystagmus was less (decrease of 50%, range 12–82%) towards the contralateral side while it remained unchanged on the ipsilateral side. The VOR in the dark and the velocity storage mechanism were not altered. For the latter, the slow build-up of optokinetic nystagmus velocity, the optokinetic afternystagmus (OKAN) and the time constant of decay for the vestibular nystagmus were evaluated. There was no spontaneous nystagmus in the light or dark and no gazeholding deficit. These data support evidence that the fastigial oculomotor region contributes direction-specifically to smooth pursuit mechanisms, without affecting the VOR and the velocity storage mechanism.     

Differential effects of bicuculline and muscimol microinjections into the vestibular nuclei on simian eye movements

Summary 1.) Eye movements were recorded in four Java monkeys (M. fascicularis) after unilateral microinjections (1 l, concentration 1 g/l) of the GABA antagonist, bicuculline, and the GABA agonist, muscimol, into oculomotor related regions of the vestibular nuclei. Eye movements were investigated in the dark and light during spontaneous eye movements, vestibular stimulation (sinusoidal: 0.2 Hz, ±40 deg/s, and velocity trapezoid: 40 deg/s² acceleration, 120 deg/s constant velocity), and visual-vestibular conflict stimulation. 2.) Bicuculline and muscimol injections consistently led to specific eye movement changes, which were maximal 5–10 min after bicuculline injection (muscimol 10–30 min), and lasted 90–120 min (muscimol 2–4 h). Control injections with NaCl (0.9%) into the responsive area and with bicuculline 2–3 mm more lateral showed no effect. 3.) Bicuculline induced a spontaneous nystagmus of 40.9 deg/s (average, range 10.5–93 deg/s), beating in 60% of the cases to the contralateral and in 40% to the ipsilateral side. The analysis of the slope of the slow phase gave no evidence for an additional gaze holding deficit. The VOR gain in the dark showed a slight decrease (pre: 0.96; post: 0.86) on average. The time constant of decay for slow phase nystagmus velocity after vestibular ramp stimulation was reduced, reflecting a velocity storage deficit. After bicuculline injections nystagmus suppression in the light and during visual-vestibular conflict stimulation was generally well preserved. 4.) After muscimol injections horizontal gaze holding was severely affected. Each saccade was followed by an exponentially decreasing postsaccadic drift with a time constant as short as 250 ms (average 414 ms). The eyes always drifted towards a null-position, which generally did not coincide with the midposition of the eye. The null-position could move up to 35 deg to the contra-lateral or ipsilateral side. The highly distorted eye movements after muscimol injections prevented VOR-measurements based on eye velocity. Instead vestibular stimulation led to a shift of the null-position with an amplitude corresponding to a gain (eye position/stimulus position) of 0.17 (average) at 0.2 Hz (±40 deg/s). Vertical eye movements did not show a major gaze holding deficit. 5.) From the experiments it can be concluded that the inhibitory transmitter GABA plays an important role for eye movement generation within the vestibular nuclei. Bicuculline induces mainly a vestibular imbalance with little evidence for a neural integrator deficit. In contrast unilateral muscimol injections lead to a complete, reversible loss of function for the common horizontal neural integrator, which converts eye velocity into eye position signals. The accompanying shift of the null-position reflects an additional vestibular imbalance.     

Neuronal activity in the flocculus of the alert monkey during sinusoidal optokinetic stimulation

Summary 1. Activity of single units was recorded in the flocculus of alert, behaving monkeys during sinusoidal optokinetic (0.02–5.0 Hz), constant velocity optokinetic, vestibular and visual-vestibular conflict stimulation. The maximal stimulus velocity for sinusoidal optokinetic stimulation at different frequencies was 40 deg/s or less (at frequencies above 1 Hz). For an amplitude series at 0.2 Hz, stimulus velocity was varied between ±10 to ±80 deg/s. In one trained monkey activity was also investigated during smooth pursuit eye movements and suppression of the vestibulo-ocular reflex by visual fixation (VOR-supp.). Only neurons which responded to 0.2 Hz (±40 deg/s) optokinetic stimulation were included in the study. 2. The majority of neurons (44 out of 59) were type I Purkinje cells (PCs), which increased their simple spike activity during optokinetic cylinder rotation to the ipsilateral recording side. The responses during other, vestibular related, paradigms allowed all these neurons to be classified as so called gaze velocity PCs. Three type II PCs were encountered, which responded similarly, but were only weakly modulated. 3. All type I PCs were modulated at frequencies of sinusoidal optokinetic stimulation between 0.05 and 2.5 Hz. PC's showed little or no modulation at 0.03 and 0.02 Hz. About half of the PC's still responded at 5.0 Hz. 4. Relative to eye velocity, the PC activity had a phase advance of about 30 deg between 0.1 and 2 Hz. It became larger at lower, and smaller at higher, frequencies. Eye velocity related sensitivity (imp/s/deg/s) was small at low stimulus frequencies and increased monotonically, on average from 0.16 at 0.02 Hz to 2.0 at 3.3 Hz. 5. Ten (out of 12) mossy fiber related input neurons were classified as visual neurons, since their activity could be related to the amount of retinal slip in all conditions. Neurons were clearly modulated at sinusoidal optokinetic stimulation up to 5 Hz. One input neuron, investigated during sinusoidal OKN, smooth pursuit eye movements, VOR and VOR-supp., behaved qualitatively like a gaze velocity PC. The remaining input neuron encoded eye velocity at 0.2 Hz optokinetic, vestibular and visual-vestibular conflict stimulation. 6. The results show that during sinusoidal and constant velocity optokinetic stimulation gaze velocity PC's do not encode eye velocity and/or eye acceleration. 7. The vestibular nuclei-flocculus complementary hypothesis (Waespe and Henn 1981) can explain PC responses to a large extent. However, a direct comparison shows that at low frequencies (particularly around 0.05 Hz) the complementary responses of most velocity storage encoding vestibular nuclei neurons and floccular PC's appears insufficient to account fully for the oculomotor response.Supported by Deutsche Forschungsgemeinschaft SFB 220, D7R.B. was a Alexander v. Humboldt fellow.     

Nystagmus induced by electrical stimulation of the vestibular and prepositus hypoglossi nuclei in the monkey: evidence for site of induction of velocity storage

Summary Electrical stimulation of the vestibular nuclei (VN) and prepositus hypoglossi nuclei (PPH) of alert cynomolgus monkeys evoked nystagmus and eye deviation while they were in darkness. At some sites in VN, nystagmus and after-nystagmus were induced with characteristics suggesting that velocity storage had been excited. We analyzed these responses and compared them to the slow component of optokinetic nystagmus (OKN) and to optokinetic after-nystagmus (OKAN). We then recorded unit activity in VN and determined which types of nystagmus would be evoked from the sites of recording. Nystagmus and eye deviations were also elicited by electrical stimulation of PPH, and we characterized the responses where unit activity was recorded in PPH. Horizontal slow phase velocity of the VN storage responses was contralateral to the side of stimulation. The rising time constants and peak steady-state velocities were similar to those of OKN, and the falling time constants of the after-nystagmus and of OKAN were approximately equal. Both the induced after-nystagmus and OKAN were habituated by stimulation of the VN. When horizontal after-nystagmus was evoked with animals on their sides, it developed yaw and pitch components that tended to shift the vector of the slow phase velocity toward the spatial vertical. Similar cross-coupling occurs for horizontal OKAN or for vestibular post-rotatory nystagmus elicited in tilted positions. Thus, the storage component of nystagmus induced by VN stimulation had the same characteristics as the slow component of OKN and the VOR. Positive stimulus sites for inducing nystagmus with typical storage components were located in rostral portions of VN. They lay in caudal ventral superior vestibular nucleus (SVN), dorsal portions of central medial vestibular nucleus (MVN) caudal to the abducens nuclei and in adjacent lateral vestibular nucleus (LVN). More complex stimulus responses, but with contralateral after-nystagmus, were induced from surrounding regions of ventral MVN and LVN, rostral descending vestibular nucleus and the marginal zone between MVN and PPH. Vestibular-only (VO), vestibular plus saccade (VPS) and tonic vestibular pause (TVP) units were identified by extracellular recording. Stimulation near type I lateral and vertical canalrelated VO units elicited typical storage responses with after-nystagmus in 23 of 29 tracks (79%). Stimulus responses were more complex from the region of neurons with oculomotor-related signals, i.e., TVP or VPS cells, although after-nystagmus was also elicited from these sites. Effects of vestibular nerve and nucleus stimulation were compared. Nerve stimulation evoked nystagmus with both a rapid and slow component and after-nystagmus. There was a more prominent rapid rise in slow phase velocity, higher peak velocities, shorter latencies and a shorter falling time constant from nerve than from nucleus stimulation. This indicates more prominent activation of rapid pathways from nerve stimulation. From a comparison of nerve- and nucleus-induced nystagmus, we infer that there was predominant activation of the network responsible for velocity storage by electrical stimulation at many sites in the VN. Microstimulation at sites in PPH elicited nystagmus with ipsilateral slow phases or ipsilateral eye deviations. Slow phase eye velocity changed rapidly at the onset of nystagmus, and peak eye velocities were about 10–15°/s lower than from VN stimulation. The nystagmus had no slow component, and it was not followed by after-nystagmus. Only burst or burst-tonic neurons were recorded in PPH. Stimulation at sites of recording of these units induced either nystagmus with a rapid component or ipsilateral eye deviation. We conclude that the slow component of optokinetic and vestibular nystagmus, attributable to velocity storage is produced in the VN, not in the PPH. We postulate that VO neurons lying in caudal ventral portions of SVN, dorsal portions of MVN and adjacent LVN are part of the network that generates velocity storage.     

Vestibular nuclei activity and eye movements in the alert monkey during sinusoidal optokinetic stimulation

Summary In the alert monkey (Macaca fascicularis) vestibular nuclei neurons and eye movements were recorded during sinusoidal optokinetic stimulation in the horizontal plane at frequencies between 0.02–3.3 Hz. Maximal stimulus velocity was generally kept constant at 40 deg/s, except for frequencies above 1 Hz. Eye movements showed a nystagmuslike pattern up to 0.2 Hz with a gain (change in eye position/change in cylinder position) greater than 0.8; at frequencies above 1 Hz the gain dropped to 0.35 at 3.3 Hz. A decrease in gain was accompanied by an increasing phase lag. Recordings in the vestibular nuclei were obtained from vestibular only and vestibular plus saccade neurons. Neurons with a strong eye position signal (vestibular plus position) were excluded. The vast majority (87%) of neurons were not modulated at 0.2 Hz or higher frequencies of sinusoidal optokinetic stimulation, and were classified as low-frequency type neurons. Compared to the response at constant stimulus velocity, sensitivity (imp·s^-1/deg·s^-1) dropped to 72% at 0.03 Hz and 16% at 0.1 Hz. A few neurons (13%) responding at 0.2 Hz (sensitivity on average 65% of the constant velocity response) were classified as high-frequency type neurons. They did not respond above 1.0 Hz and showed no modulation with individual eye movements. The results suggest that the activity in the groups of vestibular nuclei neurons tested here is insufficient to account for the eye movements in response to sinusoidal optokinetic stimulation at frequencies above 0.1 Hz. Thus additional neuronal mechanisms have to be involved in the generation of high frequency optokinetic responses, a likely structure being the flocculus in the cerebellum. Whether the high-frequency type vestibular nuclei neurons play a role for this response has yet to be determined.Supported by Deutsche Forschungsgemeinschaft SFB 200 A 2R.B. was a Alexander v. Humboldt fellow.     

Visual sensory substitution in vestibular compensation: neuronal substrates in the alert cat

The purpose of this study was to investigate adaptive changes in the activity of vestibular nuclei neurons unilaterally deprived of their primary afferent inputs when influenced by visual motion cues. These neuronal changes might account for the established role that vision plays in the compensation for posturo-kinetic deficits after the loss of vestibular inputs. Neuronal recordings were made in alert, non-paralysed cats that had undergone unilateral vestibular nerve sections. The unit responses collected in both Deiters' nuclei were compared to those previously recorded in intact cats. We analysed the extracellular activity of Deiters' nucleus neurons, as well as the optokinetic reflex (OKR) evoked during sinusoidal translation of a whole-field optokinetic stimulus in the vertical plane. In intact cats, we found the unit firing rate closely correlated with the visual surround translation velocity, and the relationship between the discharge rate and the motion frequency was tuned around an optimal frequency. The maximum firing rate modulation was generally below the 0.25 Hz stimulus frequency; unit responses were weak or even absent above 0.25 Hz. From the 4th day to the end of the 3rd week after ipsilateral deafferentation, a majority of cells was found to display maximum discharge modulation during vertical visual stimulation at 0.50 Hz, and even at 0.75 Hz, indicating that the frequency bandwidth of the visually induced responses of deafferented vestibular nuclei neurons had been extended. Consequently, the frequency-dependent attenuation in the sensitivity of vestibular neurons to visual inputs was much less pronounced. After the first 3 weeks postlesion, the unit response characteristics were very similar to those observed prior to the deafferentation. On the nucleus contralateral to the neurectomy, the maximum modulation of most cells was tuned to the low frequencies of optokinetic stimulation, as also seen prior to the lesion. We found, however, a subgroup of cells displaying well-developed responses above 0.50 Hz. Under all experimental conditions, the neuronal response phase still remained closely correlated with the motion velocity of the vertical sinusoidal visual pattern. We hypothesize that Deiters' neurons deprived of their primary afferents may transiently acquire the ability to code fast head movements on the basis of visual messages, thus compensating, at least partially, for the loss of dynamic vestibular inputs during the early stages of the recovery process. Since the overall vertical OKR gain was not significantly altered within the 0.0125 Hz–1 Hz range of stimulation after the unilateral neurectomy, it can be postulated that the increased sensitivity of deafferented vestibular neurons to visual motion cues was accounted for by plasticity mechanisms operating within the deafferented Deiters' nucleus. The neuroplasticity mechanisms underlying this rapid and temporary increase in neuronal sensitivity are discussed.     

Unidirectional habituation of vestibulo-ocular responses by repeated rotational or optokinetic stimulations in the cat

Summary 1.Unilateral habituation of the vestibuloocular reflex was produced in adult cats stimulated by repeated unidirectional velocity steps (vestibular training) or by a continuously moving visual surround (optokinetic training). — 2. Unidirectional vestibular training produced a strong asymmetry of vestibuloocular responses (VOR). Responses to velocity steps applied to the trained labyrinth were decreased both in gain and in time-constant. This effect generalized to responses to sinusoidal oscillations (0.03 Hz to 0.1 Hz), i.e. to a stimulus not used during training. — No spontaneous nystagmus was ever observed in spite of the dynamic VOR asymmetry. — 3. Unilateral vestibular habituation produced by vestibular training appeared to be a long-lasting phenomenon. It was still present 10 days after the end of training. — 4. Optokinetic responses were not affected by vestibular training. — 5. Unidirectional optokinetic training produced an increase in the slow phase velocity of optokinetic nystagmus (OKN) by about 25% in both directions. This effect did not persist for more than a few minutes. A marked spontaneous nystagmus was recorded in the dark after each session of optokinetic training, with a slow phase in the direction opposite to the previous OKN. — 6. VOR in response to velocity steps and to sinusoidal oscillations were decreased unilaterally after optokinetic training. This effect was of short duration, however, and disappeared within the interval between training sessions. This lack of retention contrasted with the prolonged effect of vestibular training.Supported by INSERM (France) and by CNR (Italy)     

Optokinetic-vestibular interaction in patients with increased gain of the vestibulo-ocular reflex

We studied optokinetic nystagmus (OKN), optokinetic afternystagmus (OKAN) and visual-vestibular interaction in five patients with markedly elevated vestibulo-ocular reflex (VOR) gain due to cerebellar atrophy. All had impaired smooth pursuit, decreased initial slow phase velocity of OKN, and impaired ability to suppress the VOR with real or imagined targets. OKN slow phase velocity gradually built up over 25–45 s, reaching normal values for low stimulus velocities (30 deg/s). Initial velocity of OKAN was increased, but the rate of decay of OKAN was normal. These findings can be explained by models that include separate velocity storage and variable gain elements shared by the vestibular and optokinetic systems.     

Conflicting visual-vestibular stimulation and vestibular nucleus activity in alert monkeys

Summary In alert Rhesus monkeys (Macaca mulatta) neuronal activity of vestibular nuclei was recorded during pure vestibular and conflicting visual-vestibular stimulation. Pure vestibular stimulation consisted of rotating the monkey about the vertical axis in complete darkness. During conflicting visual-vestibular stimulation the monkeys were rotated in the light within a vertically striped cylinder mechanically coupled to the turntable. The conflict is that although the monkey is accelerated, there is no relative movement between visual surrounding and the animal. In the conflict situation thresholds of neuronal modulation and of nystagmus were raised compared with those during pure vestibular stimulation. Nystagmus slow-phase velocity could always be dissociated from the neuronal activity, the nystagmus often being totally suppressed whereas the neuronal activity was only attenuated. This suggests a further information processing between vestibular and oculomotor nuclei in the generation of nystagmus.Supported in part by Swiss National Foundation for Scientific Research 3.672-0.77, and Emil Barell-Foundation of Hoffmann-La Roche, Basel, Switzerland     

Visual-vestibular interactions in the vestibular nuclei of the goldfish

Summary The responses of vestibular nuclei neurons of relaxed unaesthetized goldfish have been examined with trapezoid velocity stimuli under three conditions. Responses to horizontal body rotation in the dark (pure vestibular stimulation) resemble those observed in vestibular nerve afferents. Optokinetic responses to exclusive visual surround-motion are also direction-specific and, in contrast to vestibular responses, exhibit a tonic response to constant velocity. They show three different response profiles, classified A, B or C, based on the neuron's discharge rate: either increasing, decreasing or remaining constant once surround motion is maintained at constant velocity. Following these dynamic effects, optokinetic responses have a maintained modulation of resting discharge until deceleration commences. The time constants associated with the dynamic effects vary between 1 and 11 seconds. Steady-state modulation of optokinetic responses shows a weak relation to stimulus velocities exceeding 10 deg/sec. Responses to body rotation in the light were found to linearly combine the weighted vestibular and optokinetic responses so that accurate velocity information is available for sensory and motor functions independent of the neuron's vestibular (I, II) or optokinetic (A, B, C) response type. The principle of this visual-vestibular interaction is discussed with respect to multisensory processing within the vestibular nuclei.     

Optokinetic nystagmus (OKN) and optokinetic after-responses after bilateral vestibular neurectomy in the monkey

Summary The superior branch of the vestibular nerve containing peripheral axons of primary afférents originating in the lateral and anterior semicircular canals was cut bilaterally in three monkeys (vestibular neurectomy). Vertical and horizontal components of eye position were monitored by electro-oculography (EOG) during different stimulus and behavioral paradigms. Postoperatively, monkeys were unable to hold their eyes in eccentric lateral positions in complete darkness. The eyes drifted slowly back to the primary position where eye drift was minimal (null-zone). After vestibular neurectomy the time constant of the eye position integrator in darkness was 4–8 s. Constant velocity optokinetic stimuli produced peak velocities of horizontal OKN that were similar to those before operation. Consistent optokinetic after-responses could not be observed after neurectomy for stimulus durations of less than 60 s. However, with stimulus periods greater than 60–120 s a drift near the primary position of the eyes appeared in darkness which had the same direction as the slow phases of the preceding OKN. Drift velocity was too high to be explained by drift due to the imperfect eye position integrator alone. We assume that drift after prolonged optokinetic stimulation is a combination of an after-response similar as it can be observed after smooth pursuit and of drift due to an imperfect eye position integrator. Secondary optokinetic after-nystagmus was not observed after neurectomy.Supported by Swiss National Foundation for Scientific Research (Nr. 3.718-0.80 and 3.593-0.84)     

Head movements during optokinetic stimulation in the alert rabbit

Summary Pigmented rabbits with their heads free to move about the vertical axis were seated inside a rotating optokinetic drum in order to evoke the optocollic reflex (OCR). At drum velocities below 5°/s, head movements were inconsequential, and eye velocity generally matched drum velocity. At velocities between 5–15°/s head movements were irregular and slight; head velocity was less than 20% of drum velocity, and gaze was undercompensatory by 1–3°/s (retinal image motion of 1–3°/s). At drum velocities above 15°/s, and especially above 30°/s, head movements were substantial (more than 20% of the drum velocity), but gaze was undercompensatory by 60–70% of the stimulus velocity. In the same rabbits in the same test periods and conditions, the vestibulo-collic reflex (VCR) was evoked with vision with minimal gaze undercompensation relative to a stationary surround; however, when deprived of vision the VCR gain dropped. The present results support the notion that with vision, the OCR does not contribute significantly to the improvement of the VCR response, since massive undercompensation of the gaze relative to the rotating drum was required in OCR testing to evoke head movements similar to those seen in VCR tests. Due to many differences in operating characteristics of the vestibular and optokinetic systems, and due to the nature of OCR testing, there were several unexpected results: in some cases head movements did not result in summation of vestibular and optokinetic reflexes, and with sinusoidal drum rotations of about 2°/s² peak acceleration there was overcompensation (gaze moves faster than the drum) for intervals up to 20 s. Thus, optokinetically generated active head movements could produce behavior strongly contrasting with passively induced head movements in visualvestibular tests. It is tentatively concluded that in mammals there is a vestigial and specific optokinetic control of gaze and that the optokinetic control of the head is weak (relative to the eyes). However, other non-reflex mechanisms controlling head movements — such as stimulus entrainment and temporal asymmetries in the vestibular and optokinetic reflexes — must also be considered to explain all, facets of the data.This work has been supported by USPHS grant NS-17002     

Neural basis for eye velocity generation in the vestibular nuclei of alert monkeys during off-vertical axis rotation

Summary Activity of vestibular only (VO) and vestibular plus saccade (VPS) units was recorded in the rostral part of the medial vestibular nucleus and caudal part of the superior vestibular nucleus of alert rhesus monkeys. By estimating the null axes of recorded units (n = 79), the optimal plane of activation was approximately the mean plane of reciprocal semicircular canals, i.e., lateral canals, left anterior-right posterior (LARP) canals or right anterior-left posterior (RALP) canals. All units were excited by rotation in a direction that excited a corresponding ipsilateral semicircular canal. Thus, they all displayed a type I response. With the animal upright, there were rapid changes in firing rates of both VO and VPS units in response to steps of angular velocity about a vertical axis. The units were bidirectionally activated during vestibular nystagmus (VN), horizontal optokinetic nystagmus (OKN), optokinetic afternystagmus (OKAN) and off-vertical axis rotation (OVAR). The rising and falling time constants of the responses to rotation indicated that they were closely linked to velocity storage. There were differences between VPS and VO neurons in that activity of VO units followed the expected time course in response to a stimulus even during periods of drowsiness, when eye volocity was reduced. Firing rates of VPS units, on the other hand, were significantly reduced in the drowsy state. Lateral canal-related units had average firing rates that were linearly related to the bias or steady state level of horizontal eye velocity during OVAR over a range of ±60 deg/s. These units could be further divided into two classes according to whether they were modulated during OVAR. Non-modulated units (n = 5) were VO types and all modulated units (n = 5) were VPS types. There was no significant difference between the bias level sensitivities relative to eye velocity of the units with and without modulation (P>0.05). The modulated units had no sustained change in firing rate in response to static head tilts and their phases relative to head position varied from unit to unit. The phase did not appear to be linked to the modulation of horizontal eye velocity during OVAR. The sensitivities of unit activity to eye velocity were similar during all stimulus modalities despite the different gains of eye velocity vs stimulus velocity during VN, OKN and OVAR. Therefore, VO and VPS units are likely to carry an eye velocity signal related to velocity storage. For example, when unit sensitivities were related to head or surround velocity, sensitivity relative to OVAR was less than for VN or OKN. Firing rates of both vertical canal-related VO and VPS units (n= 19) were strongly modulated during OVAR, although they did not show changes in discharge rate during static head tilts relative to the spatial vertical up to a maximal 25 deg. In some cases the amplitude of the modulation increased with increases in head velocity and eye velocity. Average activity of vertical canal-related units was linearly related to steady state horizontal eye velocity in the ipsilateral direction during OVAR. The mean sensitivities of RALP units were not significantly different from those of LARP neurons (P>0.05). Together, their mean sensitivity during OVAR about a subject yaw axis was 0.34 (imp/s)/(deg/s) relative to horizontal eye velocity. This could be explained as a contribution of the vertical canals to horizontal eye velocity due to their orientation in the head. During OVAR to the ipsilateral side, the bias level of neuronal activity decreased and saturated. For steps of rotation about a vertical axis with the animal upright, the firing rates of RALP and LARP units were linearly related to stimulus velocity and eye velocity. Contralateral rotation excited the units reflecting the orientation of the semicircular canals relative to the yaw axis of rotation. RALP and LARP units also responded during horizontal optokinetic stimulation producing both OKN and OKAN. All the vertical canal units had dynamic characteristics closely related to velocity storage. Their response characteristics were consistent with the model that they contribute to horizontal slow phase velocity as part of a three-dimensional system based on a semicircular canal frame of reference. Otolith-related units (n= 5) in the vestibular nuclei showed no evidence of velocity storage and were modulated in accordance with head position during OVAR. Mean amplitude of the modulation of activity during OVAR at a 20 deg tilt and 60 deg/s rotational velocity was 24 imp/s. The data indicate that the vestibular nuclei contain the requisite signals to generate horizontal eye velocity during OVAR. VO and VPS units probably contribute to the bias or velocity storage component while otolith units mainly contribute to the oscillations in eye velocity by generating gravity dependent eye position changes during OVAR. In addition to the velocity storage component of horizontal eye velocity, the vertical VO neurons also have oscillations in their discharge patterns probably related to the vertical component of eye movements generated by the velocity storage integrator.