Robert A. McCrea

Anatomical and physiological characteristics of vestibular neurons mediating the vertical vestibulo-ocular reflexes of the squirrel monkey.

The morphology of 35 vestibular neurons whose firing rate was related to vertical eye movements was studied by injection of horseradish peroxidase intracellularly into physiologically identified vestibular axons in alert squirrel monkeys. The intracellularly injected cells were readily classified into four main groups. One group of cells, down position‐vestibular‐pause neurons (down PVPs; N = 12), increased their firing rate during downward eye positions, paused during saccades, and were located in the medial vestibular nucleus (MV) and the adjacent ventrolateral vestibular nucleus (VLV). They had axons that crossed the midline and ascended in the medial longitudinal fasciculus (MLF) to terminate in the trochlear nucleus, the lateral aspect of the caudal oculomotor nucleus, and the dorsal aspect of the rostral oculomotor nucleus. A second group of cells (N = 15) were also located in the MV and VLV, but increased their firing rate during upward eye positions, and paused during saccades. These cells had axons that crossed the midline and ascended in the contralateral MLF to terminate in the medial aspect of the oculomotor nucleus. A third group of cells (N = 4) were located in the superior vestibular nucleus, generated bursts of spikes during upward saccades, and increased their tonic firing rate during upward eye positions. These cells had axons that ascended laterally to the ipsilateral MLF to terminate in regions of the trochlear and oculomotor nuclei similar to those in which down PVPs terminated. A fourth group of cells (N = 4), located in the VLV, had axons that projected to the spinal cord, although they had firing rates that were significantly correlated with vertical eye position. Electrical stimulation of the vestibular nerve evoked spikes at monosynaptic latencies in each of the above classses of cells, six of which were injected with horseradish peroxidase.

Anatomy and physiology of intracellularly labelled omnipause neurons in the cat and squirrel monkey

SummarySaccadic omnipause neurons (OPNs) were intracellularly labelled with horseradish peroxidase (HRP) in alert cats and squirrel monkeys. The somas of OPNs were located on or near the midline in the caudal pons and their axons projected to regions of the pontomedullary reticular formation that contain the excitatory and inhibitory burst neurons.

Contributions of regularly and irregularly discharging vestibular-nerve inputs to the discharge of central vestibular neurons in the alert squirrel monkey

Abstract The discharge of neurons in the vestibular nuclei was recorded in alert squirrel monkeys while they were being sinusoidally rotated at 2 Hz. Type I position-vestibular-pause (PVP I) and vestibular-only (V I) neurons, as well as a smaller number of other type I and type II eye-plus-vestibular neurons were studied. Many of the neurons were monosynaptically related to the ipsilateral vestibular nerve. Eye-position and vestibular components of the rotation response were separated by multiple regression. Anodal currents, simultaneously delivered to both ears, were used to eliminate the head-rotation signals of irregularly discharging (I) vestibular-nerve afferents, presumably without affecting the corresponding signals of regularly discharging (R) afferents. R and I inputs to individual central neurons were determined by comparing rotation responses with and without the anodal currents. The bilateral currents, while reducing the background discharge of all types of neurons, did not affect the mean vestibular gain or phase calculated from a population of PVP I neurons or from a mixed population consisting of all type I units. From this result, it is concluded that I inputs are canceled at the level of secondary neurons. The cancellation may explain why the ablating currents do not affect the gain and phase of the vestibulo-ocular reflex. While cancellation was nearly perfect on a population basis, it was less so in individual neurons. For some neurons, the ablating currents decreased vestibular gain, while for other neurons the vestibular gain was increased. The former neurons are interpreted as receiving a net excitatory (I-EXC) I input, the latter neurons, a net inhibitory (I-INH) input. When compared with the corresponding R inputs, the I inputs were usually small and phase advanced. Phase advances were larger for I-EXC than for I-INH inputs. The sign and magnitude of the I inputs were unrelated to other discharge properties of individual neurons, including discharge regularity and the phase of vestibular responses measured in the absence of the ablating currents. Unilateral currents were used to assess the efficacy of ipsilateral and contralateral pathways. Ipsilateral pathways were responsible for almost all of the effects seen with bilateral currents. The results suggest that the vestibular signals carried by central neurons, even by those neurons receiving a monosynaptic vestibular-nerve input, are modified by polysynaptic pathways.

Dual projections of secondary vestibular axons in the medial longitudinal fasciculus to extraocular motor nuclei and the spinal cord of the squirrel monkey

SummaryRecordings were made from secondary vestibular axons in the medial longitudinal fasciculus (MLF) of barbiturate-anesthetized squirrel monkeys. Antidromic stimulation techniques were used to identify the axons as belonging to one of three classes of neurons: vestibulo-oculo-collic (VOC) neurons project both to the extraocular motor nuclei and to the spinal cord; vestibulo-ocular (VO) neurons do not have a spinal projection; and vestibulocollic (VC) neurons do not have an oculomotor projection. Galvanic stimulation was used to show that axons of all three classes received excitatory inputs from one labyrinth and inhibitory inputs from the other. VOC axons were confined to the MLF contralateral to the labyrinth from which they were excited. They made up more than half of the vestibular axons descending in the contralateral medial vestibulospinal tract (MVST), but less than one-quarter of those ascending in the contralateral MLF to the level of the oculomotor nucleus. Spinal projections were restricted to cervical segments with about half of the axons reaching segment C6. Conduction velocities, measured for Co-projecting axons, were similar for VOC and VC axons and were typically 25–50 m/s. Unlike the situation in the rabbit (Akaike et al. 1973) and cat (Akaike 1983), none of the MVST axons had conduction velocities > 75 m/s. The morphology of VOC neurons was studied by injection of horseradish peroxidase (HRP) into 60 physiologically identified axons in the MLF. Since individual axons were only stained for short distances, it was not possible to ascertain their complete branching patterns. Labeled fibers could be traced to an origin in and around the ventral lateral vestibular nucleus. This localization was confirmed by comparing the distributions within the vestibular nuclei of neurons retrogradely labeled from the upper cervical spinal cord (this study) and from the oculomotor nucleus (McCrea et al. 1987a; Highstein and McCrea 1988). VOC axons reached the contralateral MLF at the level of the abducens nucleus and immediately divided into an ascending and a descending, usually thicker, branch. Seven VOC axons could be traced to the extraocular motor nuclei; three terminated in the medial aspect of the oculomotor nucleus bilaterally and four terminated in the medial aspect of the contralateral abducens nucleus. The former axons may be part of a crossed, excitatory anterior-canal pathway; the latter, part of a similar horizontal-canal pathway. There were no terminations in the trochlear nucleus even though 12 labeled fibers passed close to it. VOC axons projected to several brainstem nuclei, including the contralateral interstitial nucleus of Cajal, cell groups in the region of the medial longitudinal fasciculus rostral to the abducens nucleus, the nucleus prepositus, the nucleus raphe obscuris, Rollers nucleus, and the paramedian medullary reticular formation. Virtually all of the above connections, except for the bilateral projection to the oculomotor nucleus, were contralateral to the cells of origin. The results in the squirrel monkey are compared with previous studies of VOC neurons in the cat (Isu and Yokota 1983; Uchino and Hirai 1984; Isu et al. 1988). In both species, VOC neurons make up a large proportion of contralaterally projecting MVST fibers. On the other hand, such dual-projecting neurons may provide a considerably smaller fraction of the secondary vestibular axons reaching the oculomotor nucleus in the monkey than they do in the cat.

Firing behaviour of squirrel monkey eye movement‐related vestibular nucleus neurons during gaze saccades

The firing behaviour of vestibular nucleus neurons putatively involved in producing the vestibulo‐ocular reflex (VOR) was studied during active and passive head movements in squirrel monkeys. Single unit recordings were obtained from 14 position‐vestibular (PV) neurons, 30 position‐vestibular‐pause (PVP) neurons and 9 eye‐head‐vestibular (EHV) neurons. Neurons were sub‐classified as type I or II based on whether they were excited or inhibited during ipsilateral head rotation. Different classes of cell exhibited distinctive responses during active head movements produced during and after gaze saccades. Type I PV cells were nearly as sensitive to active head movements as they were to passive head movements during saccades. Type II PV neurons were insensitive to active head movements both during and after gaze saccades. PVP and EHV neurons were insensitive to active head movements during saccadic gaze shifts, and exhibited asymmetric sensitivity to active head movements following the gaze shift. PVP neurons were less sensitive to ondirection head movements during the VOR after gaze saccades, while EHV neurons exhibited an enhanced sensitivity to head movements in their on direction. Vestibular signals related to the passive head movement were faithfully encoded by vestibular nucleus neurons. We conclude that central VOR pathway neurons are differentially sensitive to active and passive head movements both during and after gaze saccades due primarily to an input related to head movement motor commands. The convergence of motor and sensory reafferent inputs on VOR pathways provides a mechanism for separate control of eye and head movements during and after saccadic gaze shifts.

Contribution of vestibular nerve irregular afferents to viewing distance-related changes in the vestibulo-ocular reflex.

Abstract The contribution of irregular vestibular afferents to viewing distance-related changes in the angular vestibulo-ocular reflex (AVOR) and combined angular and linear VOR (CVOR) was studied in squirrel monkeys trained to fixate earth-stationary targets that were near (10 cm) and distant (90–170 cm) from their eyes. Perilymphatic anodal galvanic currents were used to reversibly silence irregular vestibular afferents for periods of 4–5 s during the AVOR and CVOR evoked by 0.5- to 4-Hz sinusoidal rotations (6–20°/s peak velocity) or 250–400°/s2 acceleration steps. The direction and magnitude of linear translation were changed by positioning the monkeys at different distances off the axis of turntable rotation. The effects of irregular afferent galvanic ablation (GA) on viewing distance-related changes in the AVOR were studied in four animals. Viewing distance-related changes in the AVOR could not always be evoked and were frequently small in amplitude. GA reduced viewing distance-related change in the AVOR by an average of 64% when it was present. Thus vestibular irregular afferents appear to play an important and necessary role in viewing distance-related changes in the AVOR – on those occasions when the changes occur. Viewing distance-related changes in the CVOR were large and reliably evoked. GA had very little effect on the gain or phase of viewing distance-related changes in the CVOR, although the viewing distance-related CVOR responses of individual central vestibular neurons were affected. We conclude that irregular afferents probably contribute to central signal processing related to both the AVOR and the CVOR, but the signals carried by these afferents are only essential for viewing distance-related changes in AVOR.

Activity of Ventroposterior Thalamus Neurons During Rotation and Translation in the Horizontal Plane in the Alert Squirrel Monkey

The firing behavior of 107 vestibular-sensitive neurons in the ventroposterior thalamus was studied in two alert squirrel monkeys during whole body rotation and translation in the horizontal plane. Vestibular-sensitive neurons were distributed primarily along the anterior and posterior borders of ventroposterior nuclei; three clusters of these neurons could be distinguished based on their location and inputs. Eighty-four neurons responded to rotation; 66 (78%) of them responded to rotation only and 18 (22%) to both rotation and translation. Forty-one neurons were sensitive to linear translation; 23 (56%) of them responded to translation only. The population rotational response to 0.5-Hz sinusoids with a peak velocity of 40 degrees /s showed a gain of 0.23 +/- 0.15 spike.s(-1).deg(-1).s(-1) and phase lagging behind the angular velocity by -9.3 +/- 34.1 degrees . Although rotational response amplitude increased with the stimulus velocity across the range 4-100 degrees /s, the rotational sensitivity decreased with and was inversely proportional to the stimulus velocity. The rotational response amplitude and sensitivity increased with the stimulus frequency across the range 0.2-4.0 Hz. The population response to sinusoidal translation at 0.5 Hz and 0.1 g amplitude had a gain of 111.3 +/- 53.7 spikes.s(-1).g(-1) and lagged behind stimulus acceleration by -71.9 +/- 42.6 degrees . Translational sensitivity decreased as acceleration increased and this was inversely proportional to the square root of the acceleration. Results of this study imply that changes in the discharge rate of vestibular-sensitive thalamic neurons can be approximated using power functions of the angular and linear velocity of spatial motion.

The neurophysiological substrate for the cervico-ocular reflex in the squirrel monkey.

Abstract. Passive rotation of the trunk with respect to the head evoked cervico-ocular reflex (COR) eye movements in squirrel monkeys. The amplitude of the reflex varied both within and between animals, but the eye movements were always in the same direction as trunk rotation. In the dark, the COR typically had a gain of 0.3–0.4. When animals fixated earth-stationary targets during low-frequency passive neck rotation or actively tracked moving visual targets with head movements, the COR was suppressed. The COR and vestibulo-ocular reflex (VOR) summed during passive head-on-trunk rotation producing compensatory eye movements whose gain was greater than 1.0. The firing behavior of VOR-related vestibular neurons and cerebellar flocculus Purkinje cells was studied during the COR. Passive neck rotation produced changes in firing rate related to neck position and/or neck velocity in both position-vestibular-pause neurons and eye-head-vestibular neurons, although the latter neurons were much more sensitive to the COR than the former. The neck rotation signals were reduced or reversed in direction when the COR was suppressed. Flocculus Purkinje cells were relatively insensitive to COR eye movements. However, when the COR was suppressed, their firing rate was modulated by neck rotation. These neck rotation signals summed with ocular pursuit signals when the head was used to pursue targets. We suggest that the neural substrate that produces the COR includes central VOR pathways, and that the flocculus plays an important role in suppressing the reflex when it would cause relative movement of a visual target on the retina.

Self-Motion Signals in Vestibular Nuclei Neurons Projecting to the Thalamus in the Alert Squirrel Monkey

Sixty vestibular nuclei neurons antidromically activated by electrical stimulation of the ventroposterior thalamus were recorded in two alert squirrel monkeys. The majority of these neurons were monosynaptically activated by vestibular nerve electrical stimulation. Forty-seven neurons responded to animal rotations around the earth-vertical axis; 16 of them also responded to translations in the horizontal plane. The mean sensitivity to 0.5-Hz rotations of 80 degrees /s velocity was 0.40 +/- 0.31 spikes.s(-1).deg(-1).s(-1). Rotational responses were in phase with stimulus velocity. Sensitivities to 0.5-Hz translations of 0.1 g acceleration varied from 92.2 to 359 spikes.s(-1).g(-1) and response phases varied from 10.1 degrees lead to -98 degrees lag. The firing behavior in 28 neurons was studied during rotation of the whole animal, of the trunk, and voluntary and involuntary rotations of the head. Two classes of vestibulothalamic neurons were distinguished. One class of neurons generated signals related to movement of the head that were similar either when the head and trunk move together or when the head moves on the stationary trunk. A fraction of these neurons fired during involuntary head movements only. A second class of neurons generated signals related to movement of the trunk. They responded when the trunk moved alone or simultaneously with the head, but did not respond to head rotations while the trunk was stationary.

Viewing distance related sensory processing in the ascending tract of deiters vestibulo-ocular reflex pathway.

The firing behavior of seven antidromically identified ascending tract of Deiters (ATD) neurons was recorded in one alert squirrel monkey trained to pursue moving targets and to fixate visual targets at different distances from the head during whole body rotation. 2. ATD cells generated signals related to contralateral horizontal smooth pursuit eye movements and to ipsilateral angular and linear head velocity. Most ATD neurons reversed the direction of their response to head rotation when the vestibulo-ocular reflex was canceled by fixation of a head stationary target. 3. ATD unit gains in respect to linear head velocity increased dramatically (> 4x) when a near, earth stationary target (10 cm from the eyes) was fixated, compared to the response recorded during fixation of a far target (130 to 170 cm from the eyes). Since the viewing distance related changes in the responses of ATD neurons closely parallel the changes in the responses of the eyes, the ATD appears to be an important premotor pathway for producing viewing distance related changes in the gain of the vestibulo-ocular reflex.