Functions of the nucleus of the optic tract (NOT). I. Adaptation of the gain of the horizontal vestibulo-ocular reflex.

We studied the role of the nucleus of the optic tract (NOT) in adapting the gain of the angular vestibulo-ocular reflex (aVOR) in rhesus and cynomolgus monkeys using lesions and temporary inactivation with muscimol. The aVOR gain was adaptively reduced by forced sinusoidal rotation (0.25 Hz, 60 degrees/s) in a self-stationary visual surround, i.e., a visual surround that moved with the subject, or by wearing x0.5 reducing lenses during natural head movements. The aVOR gains dropped by 20-30% after 2 h and by about 30% after 4 h. Muscimol injections caused a loss of adaptation of contraversive-eye velocities induced by the aVOR, and their gains promptly returned to or above preadapted levels. The gains of the adapted ipsiversive and vertical eye velocities produced by the aVOR were unaffected by muscimol injections. Lesions of NOT significantly reduced or abolished the animals' ability to adapt the gain of contraversive aVOR-induced eye velocities, and the monkeys were unable to suppress these contraversive-eye velocities in a self-stationary surround. The lesions did not affect ipsiversive aVOR-induced eye velocities, and the animals were still able to suppress them. Lesions of NOT also affected the unadapted or "default" aVOR gains. After unilateral NOT lesions, gains of ipsiversive aVOR-induced eye velocity were reduced, while gains of contraversive aVOR-induced eye velocity were either unaffected or slightly increased. Consistent with this, muscimol injections into the NOT of unadapted monkeys slightly reduced the gains of ipsiversive and increased the gains of contraversive-eye velocities by about 8-10%. We conclude that each NOT processes ipsiversive retinal-slip information about visual surround movement relative to the head induced by the aVOR. In the presence of visual surround movement, the retinal-slip signal is suppressed, leading to adaptive changes in the gain of aVOR-induced contraversive horizontal eye velocities. NOT also has a role in controlling and maintaining the current state of the aVOR gains. Thus, it plays a unique role in producing and supporting adaptation of the gain of the horizontal aVOR that is likely to be important for stabilizing gaze during head movement. Pathways through the inferior olive are presumably important for this adaptation.

Functions of the nucleus of the optic tract (NOT). II. Control of ocular pursuit.

Ocular pursuit in monkeys, elicited by sinusoidal and triangular (constant velocity) stimuli, was studied before and after lesions of the nucleus of the optic tract (NOT). Before NOT lesions, pursuit gains (eye velocity/target velocity) were close to unity for sinusoidal and constant-velocity stimuli at frequencies up to 1 Hz. In this range, retinal slip was less than 2 degrees. Electrode tracks made to identify the location of NOT caused deficits in ipsilateral pursuit, which later recovered. Small electrolytic lesions of NOT reduced ipsilateral pursuit gains to below 0.5 in all tested conditions. Pursuit was better, however, when the eyes moved from the contralateral side toward the center (centripetal pursuit) than from the center ipsilaterally (centrifugal pursuit), although the eyes remained in close proximity to the target with saccadic tracking. Effects of lesions on ipsilateral pursuit were not permanent, and pursuit gains had generally recovered to 60-80% of baseline after about 2 weeks. One animal had bilateral NOT lesions and lost pursuit for 4 days. Thereafter, it had a centrifugal pursuit deficit that lasted for more than 2 months. Vertical pursuit and visually guided saccades were not affected by the bilateral NOT lesions in this animal. We also compared effects of these and similar NOT lesions on optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN). Correlation of functional deficits with NOT lesions from this and previous studies showed that rostral lesions of NOT in and around the pretectal olivary nucleus, which interrupted cortical input through the brachium of the superior colliculus (BSC), affected both smooth pursuit and OKN. In two animals in which it was tested, NOT lesions that caused a deficit in pursuit also decreased the rapid and slow components of OKN slow-phase velocity and affected OKAN. It was previously shown that slightly more caudal NOT lesions were more effective in altering gain adaptation of the angular vestibulo-ocular reflex (aVOR). The present findings suggest that cortical pathways through rostral NOT play an important role in maintenance of ipsilateral ocular pursuit. Since lesions that affected ocular pursuit had similar effects on ipsilateral OKN, processing for these two functions is probably closely linked in NOT, as it is elsewhere.

Efferent pathways of the nucleus of the optic tract in monkey and their role in eye movements.

To clarify the role of the pretectal nucleus of the optic tract (NOT) in ocular following, we traced NOT efferents with tritiated leucine in the monkey and identified the cell groups they targeted. Strong local projections from the NOT were demonstrated to the superior colliculus and the dorsal terminal nucleus bilaterally and to the contralateral NOT. The contralateral oculomotor complex, including motoneurons (C-group) and subdivisions of the Edinger-Westphal complex, including motoneurons (C-group) and subdivisions of the Edinger-Westphal complex, also received inputs. NOT efferents terminated in all accessory optic nuclei (AON) ipsilaterally; contralateral AON projections arose from the pretectal olivary nucleus embedded in the NOT. Descending pathways contacted precerebellar nuclei: the dorsolateral and dorsomedial pontine nuclei, the nucleus reticularis tegmenti pontis, and the inferior olive. Direct projections from NOT to the ipsilateral nucleus prepositus hypoglossi (ppH) appeared to be weak, but retrograde tracer injections into rostral ppH verified this projection; furthermore, the injections demonstrated that AON efferents also enter this area. Efferents from the NOT also targeted ascending reticular networks from the pedunculopontine tegmental nucleus and the locus coeruleus. Rostrally, NOT projections included the magnocellular layers of the lateral geniculate nucleus (lgn); the pregeniculate, peripeduncular, and thalamic reticular nuclei; and the pulvinar, the zona incerta, the mesencephalic reticular formation, the intralaminar thalamic nuclei, and the hypothalamus. The NOT could generate optokinetic nystagmus through projections to the AON, the ppH, and the precerebellar nuclei. However, NOT also projects to structures controlling saccades, ocular pursuit, the near response, lgn motion sensitivity, visual attention, vigilance, and gain modification of the vestibulo-ocular reflex. Any hypothesis on the function of NOT must take into account its connectivity to all of these visuomotor structures.

Pretectal projections to the oculomotor complex of the monkey and their role in eye movements.

The nucleus of the optic tract (NOT) is associated with the generation of optokinetic nystagmus (OKN), whereas the olivary pretectal nucleus (ol), which lies embedded in the primate NOT, is believed to be essential for the pupillary light reflex. In this anatomical study of the pretectum, projections from NOT and ol to structures around the oculomotor nucleus were traced in the monkey, to determine which cell groups they innervated. 1. 3[H]-leucine injections were placed into NOT and ol, and labelled terminals were observed just outside the classical oculomotor nucleus (nIII), in the "C-group' and midline cell clusters, both of which contain small motoneurons of the extraocular eye muscles. In addition, there were strong projections to the lateral visceral cell column of the Edinger-Westphal complex (lvc), but not to the Edinger-Westphal nucleus (EW) itself. All of these projections were mainly contralateral. 2. NOT efferents terminated over the ipsilateral medial accessory nucleus of Bechterew (nB), but not over the adjacent nucleus Darkschewitsch. 3. Injections of a retrograde tracer into the oculomotor complex showed that the pretectal afferents described above originated mainly from the dorsomedial part of NOT and from ol. 4. The use of a transsynaptic retrograde tracer, tetanus toxin fragment (BIIb), established the monosynaptic nature of the connection between dorsomedial NOT (contralaterally) and ol (bilaterally), to the small extraocular motoneurons outside classical nIII. The "C-group' motoneurons may play a role in vergence, and lvc in pupillary constriction and depth of focus. Our results imply that NOT and ol participate in the control of some aspects of the near-response, which may be important in the generation of some components of OKN in primates.

The nucleus of the optic tract. Its function in gaze stabilization and control of visual-vestibular interaction.

1. Electrical stimulation of the nucleus of the optic tract (NOT) induced nystagmus and after-nystagmus with ipsilateral slow phases. The velocity characteristics of the nystagmus were similar to those of the slow component of optokinetic nystagmus (OKN) and to optokinetic after-nystagmus (OKAN), both of which are produced by velocity storage in the vestibular system. When NOT was destroyed, these components disappeared. This indicates that velocity storage is activated from the visual system through NOT. 2. Velocity storage produces compensatory eye-in-head and head-on-body movements through the vestibular system. The association of NOT with velocity storage implies that NOT helps stabilize gaze in space during both passive motion and active locomotion in light with an angular component. It has been suggested that "vestibular-only" neurons in the vestibular nuclei play an important role in generation of velocity storage. Similarities between the rise and fall times of eye velocity during OKN and OKAN to firing rates of vestibular-only neurons suggest that these cells may receive their visual input through NOT. 3. One NOT was injected with muscimol, a GABAA agonist. Ipsilateral OKN and OKAN were lost, suggesting that GABA, which is an inhibitory transmitter in NOT, acts on projection pathways to the brain stem. A striking finding was that visual suppression and habituation of contralateral slow phases of vestibular nystagmus were also abolished after muscimol injection. The latter implies that NOT plays an important role in producing visual suppression of the VOR and habituating its time constant. 4. Habituation is lost after nodulus and uvula lesions and visual suppression after lesions of the flocculus and paraflocculus. We postulate that the disappearance of vestibular habituation and of visual suppression of vestibular responses after muscimol injections was due to dysfacilitation of the prominent NOT-inferior olive pathway, inactivating climbing fibers from the dorsal cap to nodulouvular and flocculoparafloccular Purkinje cells. The prompt loss of habituation when NOT was inactivated, and its return when the GABAergic inhibition dissipated, suggests that although VOR habituation can be relatively permanent, it must be maintained continuously by activity of the vestibulocerebellum.

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

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 after-nystagmus (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 velocity 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.(ABSTRACT TRUNCATED AT 400 WORDS)

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

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 canal-related 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Generation of vertical and torsional rapid eye movement in the rostral mesencephalon. Experimental data and clinical implications.

The riMLF is a nucleus in the rostral mesencephalon whose bilateral destruction leads to a palsy of vertical and torsional rapid eye movements. A unilateral lesion leads to a loss of torsional rapid eye movements in only one direction, but vertical rapid movements can still be generated with some reduction in their velocity. Single neuron studies in monkeys and anatomy support the concept that the riMLF together with the PPRF are the critical areas in the brainstem to generate rapid eye movements in 3 dimensions.

Frontal eye field projection to the paramedian pontine reticular formation traced with wheat germ agglutinin in the monkey.

Injections of the retrograde tracer [125I]wheat germ agglutinin have been placed in different areas of the paramedian pontine reticular formation (PPRF), a well known premotor center for gaze control. Experiments in 5 monkeys revealed 3 major sources of input: (1) bilateral projections from the so-called frontal eye field (FEF), which is situated in the frontal cortex around the arcuate sulcus; (2) the intermediate and deep layers of mainly the contralateral superior colliculus; and (3) ipsilateral projections from brainstem structures such as the accessory oculomotor nuclei (nucleus interstitialis of Cajal, nucleus of Darkschewitsch, and nucleus of the posterior commissure), the mesencephalic reticular formation, the vestibular nuclei, the nucleus prepositus hypoglossi, and the cerebellar fastigial nucleus. The results are compared with previous anatomical investigations and confirm the electrophysiologically demonstrated FEF-PPRF-abducens disynaptic pathway.

Experimental gaze palsies in monkeys and their relation to human pathology.

Lesions were placed in the paramedian pontine reticular formation ( PPRF ) of monkeys and the resulting gaze palsies studied. Brainstem regions were identified by single cell recordings before kainic acid was injected to selectively destroy neuronal cell bodies in the vicinity. Unilateral PPRF lesions led to a loss of all rapid eye movements towards the ipsilateral side. Deficits were identical to those after experimental electrolytic lesions in monkeys, or structural lesions in humans. Bilateral PPRF lesions produced two different syndromes. Rostral PPRF lesions led to a selective loss of horizontal rapid eye movements leaving vertical movements intact. Caudal PPRF lesions led in addition to a severe disruption of vertical rapid eye movements.

Counterdrifting of the eyes: additional findings and hypothesis.

Electro-oculograms for monitoring eye movements and eye positions were performed in patients having a prolonged episode of acute peripheral vestibulopathy. During the course of such illness counterdrifting eye movements have been observed. Counterdrifting is defined as slow eye movements which develop in the direction opposite to the primary drift (i.e. the slow phase of spontaneous nystagmus), that occur when lateral gaze is attempted in the dark at eye positions on the side ipsilateral to the vestibulopathy. Counterdrifting appears always to be accompanied or followed by some recovery of labyrinthine function on the side of vestibular failure, and in 2 patients it was associated with so-called recovery nystagmus. It has not been observed after vestibular neurectomy. The hypothesis is put forward that counterdrifting could be an oculomotor phenomenon--centripetal drifting--similar to that underlying Alexander's modification of acute vestibular spontaneous nystagmus.

The superior vestibular nucleus: an intracellular HRP study in the cat. I. Vestibulo-ocular neurons.

Superior vestibular neurons were penetrated with horseradish peroxidase (HRP)-loaded glass microelectrodes in anesthetized cats. Responses to electrical stimulation of the oculomotor complex and the vestibular nerves were characterized and selected neurons were injected with HRP. Neurons antidromically activated by oculomotor complex stimulation were generally monosynaptically excited by the ipsilateral vestibular nerve. Notable was the absence of strong commissural inhibition by stimulation of the contralateral vestibular nerve. Light microscopy of antidromically identified injected cells demonstrated that these cells are predominantly located at the central levels of the superior vestibular nucleus along the incoming vestibular nerve fibers but a few are found at more caudal levels. Cell bodies, elongated or pyramidal, are mainly medium-sized to large (30-50 micrometers). Dendritic trees extend in a plane at an acute to the collaterals of the vestibular nerve fibers. Dendrites remain within the nuclear territory and generally display an isodendritic branching pattern. Dendritic spines and appendages are mainly distributed on secondary and distal dendrites. A few terminal enlargements similar to growth cones are observed in these neurons. Axons of these neurons project rostrally via the medial longitudinal fasciculus, while a minor projection via the brachium conjunctivum is also found. Axon collaterals, when present, originate in the nucleus itself and in the pontine reticular formation.

The superior vestibular nucleus: an intracellular HRP study in the cat. II. Non-vestibulo-ocular neurons.

Superior vestibular neurons were penetrated with horseradish peroxidase (HRP)-loaded glass microelectrodes in anesthetized cats and identified electrophysiologically following electrical stimulation of the vestibular nerves and oculomotor complex. Neurons that were not antidromically activated from the oculomotor complex were stained by intracellular injection of horseradish peroxidase. Three types of neurons are identified according to their initial axonal trajectories into the cerebellum, the dorsal pontine reticular formation, or the brachium conjunctivum. Ipsilateral vestibular nerve input to all neurons is primarily monosynaptic and excitatory, whereas the contralateral is inhibitory. The neurons are located in the periphery of the superior vestibular nucleus. Soma diameters range from 20.5 micrometers to 44 micrometers. Most neurons exhibit globular and ovoid cell bodies. The dendritic arbors are intermediate between iso- and allodendritic branching patterns. The few spines and dendritic appendages present are distributed mainly distally on the dendrites. Soma size does not correlate with axon diameter, number of dendrites, or dendritic territories.

Eye position and head velocity signals are conveyed to medial rectus motoneurons in the alert cat by the ascending tract of Deiters'.

Eye position and head velocity signals are conveyed to medial rectus extraocular motoneurons in the alert cat by the ascending tract of Deiters'. Physiologically and behaviorally identified ascending Deiters' neurons have been injected intra-axonally and their morphology studied.