Behavior of neurons in the abducens nucleus of the alert cat--I. Motoneurons

The activity of 53 antidromically identified abducens motoneurons was analyzed in alert cats during spontaneous and vestibular induced eye movements. Conduction velocities ranged from 13 to 70 m/s and all motoneurons increased their discharge rates with successive eye positions in the abducting direction. Motoneurons were recruited from -19 degrees to +7 degrees. Within the oculomotor range frequency saturation was never observed for any cell. The slope of rate-position (k) relationships ranged from 2 to 17.7 spikes/s/deg (n = 40, mean 8.7 +/- 2.5). Regression analysis showed that the rate-position plots could be fit by straight lines but in most cases exponential curves produced slightly better statistical fits. Steeper slopes suggest that successively larger increases in k are required for the lateral rectus muscle to maintain more eccentric fixations in the on direction. Interspike intervals for a constant eye position exhibited low variability (less than 3.5%) for fixations shorter than 1 s. Over longer periods, variability increased in proportion to the duration of the fixation in exponential-like fashion up to 14%. Abducens motoneurons showed considerable variability in frequency during repeated fixations of the same eye position. Discharge rates were found to depend upon both the direction of the previous eye movement and, more importantly, the animal's level of alertness. The rate-position regression lines for fixation periods after saccades in the on direction significantly differed in slopes (100%) and thresholds (20%) from those in the off direction. The observed static hysteresis in abducens motoneuron behavior was in opposite direction to that previously described for the mechanical properties of the lateral rectus. This suggests both neural and mechanical factors are significantly involved in determining final eye position. The animal's level of alertness was evaluated in this study by counting the number of saccadic movements/s occurring in "alert" (1 +/- 0.2 saccades/s), and "drowsy" (0.5 +/- 0.2 saccades/s) circumstances. Comparison of the rate-position regression lines between the two conditions showed a significant decrease in slopes (100%) and elevation of thresholds (70%). Discharge rate of abducens motoneurons increased abruptly 8.9 +/- 2.8 ms prior to saccades in the horizontal on direction, and decreased 14.8 +/- 4.05 m before saccades in the off direction. During purely vertical saccades the firing frequency of abducens motoneurons did not change. Burst frequency did not saturate during saccades, but increased with saccadic velocity in a linear fashion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Behavior of neurons in the abducens nucleus of the alert cat--III. Axotomized motoneurons

The effects of peripheral and central VIth nerve axotomy on abducens nucleus synaptic potentials of vestibular origin and the ultrastructure of intracellularly labeled abducens motoneurons were examined in the anesthetized cat. Subsequent experiments explored the activity of identified abducens motoneurons during spontaneous and vestibular induced eye movements in alert cats prepared for chronic recordings of eye movements, single units and field potentials. Following axotomy the typical disynaptic inhibition of abducens motoneurons induced by electrical stimulation of the ipsilateral vestibular nerve either disappeared or was reduced for 5-30 days. Disynaptic activation produced by contralateral VIIIth nerve stimulation was apparently not affected. These changes were accompanied at the ultrastructural level by a decrease of axosomatic pleiomorphic synaptic endings. No changes were observed in either the number or distribution of synaptic endings on proximal and distal dendrites. Although not expected by results obtained in acute experiments, axotomized motoneurons showed a decreased excitability in the behavioral paradigm. Amplitude of the abducens antidromic field potential was significantly reduced 4-6 days following axotomy and frequent failures were observed in the antidromic somadendritic invasion of single motoneurons. Somatic invasion was obtained by the simultaneous presentation of appropriate visual and/or vestibular synaptic activity. Chronic recordings of field potentials showed their amplitude to recover in 30-40 days. The spontaneous and vestibular induced activity of identified axotomized motoneurons during this period of time differed in several aspects from controls. Motoneurons could not maintain tonic activity during eye fixations and they showed short, low frequency, bursts of activity that followed, rather than preceded, on-directed saccades. In some cases axotomized motoneurons fired during horizontal off-directed and vertical saccades. Position and velocity gains of axotomized motoneurons were lower than control values. The effects of central axotomy were always larger and of longer duration than those following peripheral axotomy. Structural and functional properties influenced by axotomy seemed to recover in 2-3 months, but with independent time courses. The present results differ in many aspects from those described after axotomy in spinal and hypoglossal motoneurons. In addition, they point out that behavior or axotomized neurons in chronic preparations are not predictable on the basis of those described in acute experiments.     

Behavior of reticular,vestibular and prepositus neurons terminating in the abducens nucleus of the alert cat

Summary The activity of pontomedullary reticular, vestibular, and prepositus neurons has been recorded in the alert cat during spontaneous and vestibular-induced eye movements. Neurons were identified by their antidromic activation from the abducens nucleus. Spikes of these neurons were used to trigger the recording of field potentials in the abducens nucleus. The analysis by post-spike averaging of the field potentials showed the presence of a trifold system of reciprocal (excitatory and inhibitory) direct projections that originated in the above nuclei and terminated in the abducens nucleus with a distinctly graded effectiveness. This trifold afferent system is involved in the generation of fast eye movements, slow compensatory movements of vestibular origin, and eye fixation, respectively.     

Behavior of accessory abducens and abducens motoneurons during eye retraction and rotation in the alert cat

1. The activity of both accessory abducens (Acc Abd) and abducens (Abd) motoneurons (Mns) was recorded in the alert cat during eye retraction and rotational eye movements. Cats were fitted with two scleral coils, one measured rotational eye movements directly and the other retraction by distinguishing the translational component. 2. Acc Abd and Abd Mns were identified following antidromic activation from electrical stimulation of the ipsilateral VIth nerve. 3. In response to corneal air puffs, bursts of spikes were produced in all (n = 30) Acc Abd Mns. The burst began 7.2 +/- 1.2 (SD) ms after onset of the air puff and 8.9 +/- 1.9 ms before eye retraction. 4. Acc Abd Mns were silent throughout all types of rotational eye movements, and tonic activity was not observed during intervals without air-puff stimulation. 5. In contrast, all (n = 50) identified Abd Mns exhibited a burst and/or pause in activity preceding and during horizontal saccades as well as a tonic activity proportional to eye position. 6. Only 10% of Abd Mns fired a weak burst of spikes in response to air-puff stimulation. 7. We conclude that Acc Abd Mns are exclusively involved in eye retraction in the cat and that only a few Abd Mns have an eye-retraction signal added to their eye position and velocity signals. Thus any rotational eye-movement response described in retractor bulbi muscle must result from innervation by Mns located in the Abd and/or the oculomotor nuclei. 8. The organization of the prenuclear circuitry and species variation are discussed in view of the nictiating membrane extension response measured in associative learning.     

Histochemical localization of acetylcholinesterase in relation to motor neurons and internuclear neurons of the cat abducens nucleus

Summary Three distinct patterns of AChE localization have been observed in relation to cat abducens motor neurons and internuclear neurons labelled by retrograde transport of horseradish peroxidase. First, AChE was localized predominantly within cisternae of granular endoplasmic reticulum and agranular reticulum of motor neuron somata, dendrites and axons, but was absent from internuclear neurons. AChE was also associated with saccules of the Golgi apparatus in the motor neurons, but was was absent from all other cytoplasmic organelles. Second, AChE was observed on the soma-dendritic and axonal surface membrane of the motor neurons, particularly at sites of apposition of synaptic endings of all morphological types, but was usually absent from the surface membranes of internuclear neurons. Third, AChE was associated both extracellularly and intracellularly with certain synaptic endings that contained spheroidal synaptic vesicles and that contacted both motor neurons and internuclear neurons. A similar pattern of staining of synaptic endings was observed at the neuromuscular junctions in the lateral rectus muscle. Axotomy of the VIth nerve resulted in loss of intracellular AChE associated with the Golgi apparatus and extracellular AChE on the somatic surface membrane of the motor neurons. The patterned localization of AChE contrasted with the localization of butyrylcholinesterase, which was associated predominantly with astrocytes. The findings suggest different roles of AChE as a function of the different patterns of localization.     

Effects of initial eye position on saccade-related behavior of abducens nucleus neurons in the primate

Previous work suggests that when the eye starts at different orbital initial positions (IPs), the saccade control system is faced with significant nonlinearities. Here we studied the effects of IP on saccade-related firing of monkey abducens neurons by either isolating saccade variables behaviorally or applying a multiple linear regression analysis. Over a 50 degrees range of IPs, we could select 10 degrees horizontal saccades with identical velocity profiles, which would require identical control signals in a linear system. The bursts accompanying ipsiversive saccades for IPs above the threshold for steady firing were quite similar. The excess burst rate above steady firing was either constant or decreased with ipsiversive IP, and both the number of excess spikes in the burst and burst duration were nearly constant. However, for ipsiversive saccades from IPs below threshold, both peak burst rate (6.82 +/- 1.38 spikes.s(-1).deg(-1)) and burst duration (0.67 +/- 0.28 ms/deg) increased substantially with ipsiversive IPs. Moreover, the pause associated with contraversive saccades shortened considerably with ipsiversive IPs (mean 1.2 ms/deg). This pattern of results for pauses and for bursts below threshold suggests the presence of a significant nonlinearity. Abducting saccades are produced by the net force of agonist lateral rectus (LR) and antagonist medial rectus (MR) muscles. We suggest that the decreasing force in the MR muscle with IPs in the abducting direction requires a more vigorous burst in LR motoneurons, which appears to be generated by a combination of saturating and nonsaturating burst commands and the recruitment of additional abducens neurons.     

Trunk position influences vestibular responses of fastigial nucleus neurons in the alert monkey

Vestibulospinal reflexes play an important role for body stabilization during locomotion and for postural control. For an appropriate distribution of vestibular signals to spinal motoneurons, the orientation of the body relative to the head needs to be taken into account. For different trunk positions, identical vestibular stimuli must activate different sets of muscles to ensure body stabilization. Because the cerebellar vermis and the underlying fastigial nucleus (FN) might be involved in this task, vestibular neurons in the rostral FN of alert rhesus monkeys were recorded during sinusoidal vestibular stimulation (0.1-1.0 Hz) in the roll and pitch planes at different trunk-re-head positions (center and +/-45 degrees ). From the sensitivity and phase values measured in these planes, the response properties in the intermediate planes and the stimulus orientation eliciting the optimal response [response vector orientation (RVO)] were calculated. In most neurons, the RVOs rotated systematically with respect to the head, when trunk-re-head position was altered, so that they tended to maintain their orientation with respect to the trunk. Sensitivity and phase at the RVO were not affected. This pattern was the same for neurons in the right and left FN and independent of stimulus frequency. The average sensitivity of this partially compensatory RVO shift in response to trunk-re-head displacements, evaluated by linear regression analyses, was 0.59 degrees / degrees (n = 73 neurons). These data show that FN neurons may encode vestibular information in a coordinate system that is closer to a trunk-centered than to a head-centered reference frame. They indicate an important role of this nucleus in motor programs related to posture and gait control.     

Motor unit responses in the lateral rectus muscle of the cat: intracellular current injection of abducens nucleus neurons.

Single motor units of the cat's lateral rectus muscle were activated with short intracellular current pulses delivered through an intracellular micropipette penetrating a single motoneuron, and the mechanical responses in the muscle were recorded. Lateral rectus unit responses fell within the same range as those obtained earlier with extracellular stimulation of inferior oblique units, confirming that in the latter case single and not multiple motor units had been studied. It was also found that both fast and slow contracting muscle units were connected to fast conducting, large size motoneurons. The organization of motor unit recruitment in eye movements would thus seem different from the recruitment pattern in limb muscles. Intracellular stimulation of abducens nucleus "interneurons" did not initiate contractions at the ipsilateral lateral rectus muscle. These "interneuron", therefore did not appear to have excitatory inputs to the abducens motoneurons, but may be involved in relaying information to the other extraocular muscle nuclei or to other brain centers.     

Discharge patterns and recruitment order of identified motoneurons and internuclear neurons in the monkey abducens nucleus

1. Single neurons in the abducens nucleus were recorded extracellularly in alert rhesus macaques trained to make a variety of eye movements. An abducens neurons was identified as a motoneuron (MN) if its action potentials triggered an averaged EMG potential in the lateral rectus muscle. Abducens internuclear neurons (INNs) that project to the oculomotor nucleus were identified by collision block of spontaneous with antidromic action potentials evoked with a stimulating electrode placed in the medial rectus subdivision of the contralateral oculomotor nucleus. 2. All abducens MNs and INNs had qualitatively similar discharge patterns consisting of a burst of spikes for lateral saccades and a steady firing whose rate increased with lateral eye position in excess of a certain threshold. 3. For both MNs and INNs the firing rates associated with different, constant eye positions could be described accurately by a straight line with slope, K (the eye position sensitivity in spikes.s-1.deg-1), and intercept, T (the eye position threshold for steady firing). For different MNs, K increased as T varied from more medial to more lateral values. In contrast, the majority of INNs already were active for values of T more medial than 20 degrees and showed little evidence of recruitment according to K. 4. During horizontal sinusoidal smooth-pursuit eye movements, both MNs and INNs exhibited a sinusoidal modulation in firing rate whose peak preceded eye position. From these firing rate patterns, the component of firing rate related to eye velocity, R (the eye velocity sensitivity in spikes.s-1.deg-1.s-1), was determined. The R for INNs was, on average, 78% larger than that for MNs. Furthermore, R increased with T for MNs, whereas INNs showed no evidence of recruitment according to R. If, as in the cat, the INNs of monkeys provide the major input to medial rectus MNs and if simian medial rectus MNs behave like our abducens MNs, then recruitment order, which is absent in INNs, must be established at the MN pool itself. 5. Unexpectedly, the R of MNs decreased with the frequency of the smooth-pursuit movement. Furthermore, the eye position sensitivity, K, obtained during steady fixations was usually less than that determined during smooth pursuit. Therefore, conclusions about the roles of MNs and premotor neurons based on how their R and K values differ must be viewed with caution if the data have been obtained under different tracking conditions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Visual motion response properties of neurons in dorsolateral pontine nucleus of alert monkey

1. In this study we sought to characterize the visual motion processing that exists in the dorsolateral pontine nucleus (DLPN) and make a comparison with the reported visual responses of the middle temporal (MT) and medial superior temporal (MST) areas of the monkey cerebral cortex. The DLPN is implicated as a component of the visuomotor interface involved with the regulation of smooth-pursuit eye movements, because it is a major terminus for afferents from MT and MST and also the source of efferents to cerebellar regions involved with eye-movement control. 2. Some DLPN cells were preferentially responsive to discrete (spot and bar) visual stimuli, or to large-field, random-dot pattern motion, or to both discrete and large-field visual motion. The results suggest differential input from localized regions of MT and MST. 3. The visual-motion responses of DLPN neurons were direction selective for 86% of the discrete visual responses and 95% of the large-field responses. Direction tuning bandwidths (full-width at 50% maximum response amplitude) averaged 107 degrees and 120 degrees for discrete and large-field visual motion responses, respectively. For the two visual response types, the direction index averaged 0.95 and 1.02, indicating that responses to stimuli moving in preferred directions were, on average, 20 and 50 times greater than responses to discrete or large-field stimulus movement in the opposite directions, respectively. 4. Most of the DLPN visual responses to movements of discrete visual stimuli exhibited increases in amplitude up to preferred retinal image speeds between 20 and 80 degrees/s, with an average preferred speed of 39 degrees/s. At higher speeds, the response amplitude of most units decreased, although a few units exhibited a broad saturation in response amplitude that was maintained up to at least 150 degrees/s before the response decreased. Over the range of speeds up to the preferred speeds, the sensitivity of DLPN neurons to discrete stimulus-related, retinal-image speed averaged 3.0 spikes/s per deg/s. The responses to large-field visual motion were less sensitive to retinal image speed and exhibited an average sensitivity of 1.4 spikes/s per deg/s before the visual response saturated. 5. DLPN and MT were quantitatively comparable with respect to degree of direction selectivity, retinal image speed tuning, and distribution of preferred speeds. Many DLPN receptive fields contained the fovea and were larger than those of MT and more like MST receptive fields in size.(ABSTRACT TRUNCATED AT 400 WORDS)     

Eye movement related activity and morphology of second order vestibular neurons terminating in the cat abducens nucleus

Summary Intracellular records were obtained from axons of second order vestibular neurons in, and around, the left abducens nucleus in alert cats implanted with stimulating electrodes on both vestibular nerves and the left VIth nerve. Twelve secondary vestibular neurons were identified by their increase in firing rate with horizontal head rotation to the left and/or increasing eye position to the right. Following HRP injection, somatic location, axonal trajectory and termination sites were determined. Each of the above cells collateralized extensively in the abducens nucleus in a fashion consistent with their being either inhibitory (n = 7; left) or excitatory (n = 6; right) vestibular neurons in the disynaptic horizontal vestibulo-ocular reflex pathway. These vestibular neurons also arborized extensively in other posterior brainstem eye-movement related areas as well as sending an axon to the spinal cord.This work was supported by CNRS, NS-13742, and EY-02007     

Computer-aided reconstructive morphology of the baboon abducens nucleus

Our previous effort at reconstructive morphology included the marriage of the horseradish peroxidase (HRP) neurohistochemical method to a Lucite plate reconstruction technique. Limitations imposed by this combination of methods has led us to develop a computer-based system that utilizes image-processing techniques and the data obtained from HRP-processed serial light microscope sections. Labeled neurons of the baboon abducens nucleus were identified by HRP conjugated to wheat ger agglutinin. Using the resulting serial sections and a unique imaging process involving a pattern recognition algorithm, our computer-based system automatically differentiates neuronal from nonneuronal features, delineates the surface boundaries of the neuronal population, and then assembles these serial sections into a solid three-dimensional structure that can be rotated and further analyzed. A computer-generated solid model of this neuronal population has been reconstructed and reproduced in a two-dimensional publishable format. It is anticipated that with further development this system will be able to utilize data from the same specimen to study spatial relations through three-dimensional reconstruction, as well as to study the quantitative morphology of a neuronal population. Other computer-aided systems are noted, as are the advantages and shortcomings of the present method.     

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.