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L E Mays

Publications and source records attributed to L E Mays.

32 records · Page 2Linked to original sources
PubMed1988

Neuropharmacological correlates of the motor syndrome of the genetically dystonic (dt) rat.

The research program described here has focused primarily on identifying sites of dysfunction in the central nervous system of rat mutants described as dystonic. The evidence strongly favors the position that there is a defect in the cerebellum of the dt rat. At present it seems reasonable to propose as a working hypothesis that there is a defect in the Purkinje cells that renders these neurons less sensitive to the excitatory neurotransmitters released by the climbing and parallel fibers. The finding that an abnormality in GAD activity in the deep cerebellar nuclei is relatively localized when first detected but spreads over time as the motor syndrome intensifies may indicate that there is a progressive decline in the function of the Purkinje cells. The fact that electrophysiological techniques detect a mixture of relatively normal and abnormal Purkinje cell activity in animals with advanced symptoms is consistent with such a proposal. Finding significant abnormalities in the cerebellum of the dt rat does not necessarily mean that this is the site of the primary defect responsible for the motor syndrome seen in these animals. We have failed to detect any signs of dysfunction in the basal ganglia, the presumed locus of a defect in human torsion dystonia. However, our investigations have been limited almost exclusively to the striatum. Thus, the possibility of defects at other sites, such as the globus pallidus or thalamus must be considered. Although we have not yet demonstrated that the abnormalities detected in the cerebellum are causally related to the behavior of the dt rat, the behavioral syndrome is consistent with a cerebellar defect. It has been suggested that the cerebellum is important for the continuing calibration of coordinated motor behavior. Important observations on the effects of cerebellar lesions have come from the study of the oculomotor system. Lesions in the cerebellum have been shown to eliminate the ability to recalibrate the saccadic eye movement system and to destroy the adaptive plasticity of the vestibulo-ocular reflex A cerebellar defect could result in a failure in motor learning or in the calibration of motor systems that must take place as the rat pup masters adult patterns of locomotion. We note that lesions of the climbing fiber system with 3-AP lead to some of the same biochemical effects seen in dt rats but do not produce an identical behavioral syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1988

Spontaneous and harmaline-stimulated Purkinje cell activity in rats with a genetic movement disorder.

The genetically dystonic rat (dt) displays a complex movement disorder in the absence of morphological defects in the nervous system. This mutant is also insensitive to the tremorogenic effects of harmaline. Because harmaline is known to act on the cells of the inferior olive to induce activity at the tremor frequency in the olivocerebellobulbar pathway, this pathway has been investigated as a possible site of a defect in the dt rat. Biochemical studies suggested the presence of abnormalities at the level of the Purkinje cell or its afferent input. Thus, the present study investigated the harmaline response of Purkinje cells in dt rats and unaffected littermate controls with extracellular single-unit recording techniques. The spontaneous, simple spike and complex spike firing rates of dt rats were significantly lower than those of normal littermate controls. In normal rats, 2 responses to systemic harmaline injection were seen. Simple spikes were either completely suppressed for periods of 30-180 min, or were intermittently suppressed, pausing repeatedly for periods of 1-18 sec. Cells that showed complete suppression of simple spike activity also showed increased frequency and rhythmicity of complex spikes. In dt rats, intermittent simple spike responses were seen in a proportion (41%) similar to that in normal rats (53%). However, the proportion of cells showing high-frequency, rhythmic, complex spikes and complete suppression of simple spikes was low in the dt rats in comparison with littermate controls (18 versus 47%). In addition, 41% of the cells from dt rats displayed no change, or an anomalous change, in firing patterns in response to harmaline. Since the rhythmic activation of olivary neurons that results in the rhythmic, complex spike discharge of Purkinje cells is assumed to be responsible for the appearance of harmaline tremor, the failure of the dt rat to display tremor is most likely due to a failure at the olivocerebellar level, rather than at a site efferent to the cerebellum.

Action Potentials↗
PubMed1987

Eye movements induced by pontine stimulation: interaction with visually triggered saccades.

1. Rhesus monkeys were trained to look to brief visual targets presented in an otherwise darkened room. On some trials, after the visual target was extinguished but before a saccade to it could be initiated, the eyes were driven to another orbital position by microstimulation of the paramedian pontine reticular formation. If, as current models of the saccadic system suggest, a copy of the motor command is used as a feedback signal of eye position, failure to compensate for stimulation-induced movements would indicate that stimulation occurred at a site beyond the point from which the eye position signal was derived. 2. Animals compensated for perturbations of eye position induced by stimulation of most pontine sites by making saccades that directed gaze to the position of the visual target. With stimulation at other pontine sites, compensatory saccades did not occur. 3. Pontine stimulation sometimes triggered, prematurely, impending visually directed saccades. The direction and amplitude of the premature movement depended upon the location of the briefly presented visual target. The amplitude of the premature movement was also a function of the interval between the stimulation train and the impending saccade. These data suggest that input signals for the horizontal and vertical pulse/step generators develop gradually during the presaccadic interval. Saccade trigger signals need to be delayed until the formation of these signals is completed. 4. The implications of these findings for models of the saccadic system are discussed. Robinson's local feedback model of the saccadic system can explain compensation for pontine stimulation-induced changes in eye position but cannot easily account for the failure to compensate for perturbations in eye position produced by stimulation at other sites. Modified versions of Robinson's model, which assume that the input signal to the pulse/step generator is the desired displacement of the eye, can account for both compensation and the failure to compensate since two separate neural integrators are employed. However, these models ignore kinematic arguments that commands to the extraocular muscles must specify the absolute position of the eye in the orbit rather than a relative movement from a previous position.

Abducens Nerve↗
PubMed1986

Neural control of vergence eye movements: neurons encoding vergence velocity.

Single-unit recordings were made from midbrain areas in monkeys trained to make both conjugate and disjunctive (vergence) eye movements. Previous work had identified cells with a firing rate proportional to the vergence angle, without regard to the direction of conjugate gaze. The present study describes the activity of neurons that burst for disjunctive eye movements. Convergence burst cells display a discrete burst of activity just before and during convergence eye movements. For most of these cells, the profile of the burst is correlated with instantaneous vergence velocity and the number of spikes in the burst is correlated with the size of the vergence movement. Some of these cells also have a tonic firing rate that is positively correlated with vergence angle (convergence burst-tonic cells). Divergence burst cells have similar properties, except that they fire for divergent and not convergent movements. Divergence burst cells are encountered far less often than convergence burst cells. Both convergence and divergence burst cells were found in an area of the mesencephalic reticular formation just dorsal and lateral to the oculomotor nucleus. Convergence burst cells were also recorded in another more dorsal mesencephalic region, rostral to the superior colliculus. Both of the areas also contain cells that encode vergence angle. Models of the vergence system derived from psychophysical data imply the existence of a vergence integrator, the output of which is vergence angle. Some models also suggest the presence of a parallel element that improves the frequency response of the vergence system, but has no effect on the steady-state behavior of the system. Vergence burst cells would be suitable inputs to a vergence integrator. By providing a vergence velocity signal to motoneurons, they may improve the dynamic response of the vergence system. The behavior of vergence burst cells during vergence movements is similar to that of the medium-lead burst cells during saccades. The proposed roles for vergence velocity cells are analogous to those of the saccadic burst cells. In this respect, the neural organization of the vergence system resembles that of the saccadic system, despite the distinct difference in the kinematics of these two types of eye movements.

Action Potentials↗
PubMed1986

Long- and short-term monocular deprivation in the rhesus monkey: effects on visual fields and optokinetic nystagmus.

Monkeys with 1 eyelid sutured within 2 weeks of birth for 7 or 14 d (short-term monocular deprivation, n = 5) or for 18-26 months (long-term monocular deprivation, n = 5) were tested for visual and oculomotor function at approximately 2 years of age. Long-term monocularly deprived animals were behaviorally blind when visual inputs were restricted to the deprived eye. There was no sparing of the monocular segment of the visual field, and optokinetic nystagmus could not be elicited even with vertical stripes up to 15 degrees in width. These behavioral deficits could not be accounted for by optical or retinal abnormalities. In contrast, short-term monocularly deprived animals displayed normal visual fields and optokinetic nystagmus was driven by both eyes. Slow-phase gain was reduced and directional asymmetries were observed when optokinetic stimulation was restricted to the deprived eye.

Animals↗
PubMed1984

Neural control of vergence eye movements: convergence and divergence neurons in midbrain.

Animals with binocular single vision use disjunctive (vergence) eye movements to align the two eyes on a visual target. Several lines of evidence suggest that conjugate and vergence eye movement commands are generated independently and combined at the medial rectus motoneurons. If this were true, then a pure vergence eye-position signal should exist. This signal would be proportional to the horizontal angle between the eyes (vergence angle), without regard to the direction of conjugate gaze. The purpose of this experiment was to identify and study neurons that carry a pure vergence signal. Extracellular unit recordings were made from midbrain and pontine sites in monkeys trained to track visual targets moving in the horizontal, vertical, and depth (or target vergence) planes. The most commonly encountered neuron that had a vergence signal was the convergence cell. These units had a firing rate that was linearly proportional to the convergence angle; their activity was unaffected by changes in conjugate gaze. Changes in convergence cell activity preceded the change in vergence angle slightly. Convergence cell activity increased for increased convergence regardless of whether the change was in response to purely accommodative or disparity cues. Divergence cells were found far less frequently. These cells were similar to convergence cells except that they decreased their firing rate for increases in convergence. The activity of divergence cells was unaffected by changes in the direction of conjugate gaze. Both convergence and divergence cells were found, intermixed, in the mesencephalic reticular formation must outside the oculomotor nucleus. Most cells with a vergence signal were found within 1-2 mm of the nucleus. These results support the view that conjugate and vergence signals are generated independently and are combined at the extraocular motoneurons. Convergence cells seem ideally suited to provide the vergence signal required by the nearby medial rectus motoneurons.

Accommodation, Ocular↗
PubMed1984

Neural control of vergence eye movements: activity of abducens and oculomotor neurons.

Single-unit recordings were made from neurons with horizontal eye position sensitivity in the oculomotor and abducens nuclei in alert monkeys. The animals were trained to perform a visual tracking task that resulted in conjugate eye movements or symmetrical vergence movements. Scatterplots were obtained for unit firing rate as a function of the position of the ipsilateral eye for both types of movement. The slopes of the linear regression line were computed for conjugate (kc) and vergence movements (kv). Previous recording studies implied that kv should be equal to kc for most, if not all, abducens and oculomotor neurons. Other lines of evidence suggested that kv should be zero for a substantial proportion of abducens neurons. In the abducens nucleus, we found some cells for which kv matched kc, and a few cells with a kv value of zero. However, the majority of abducens units had vergence signals that were neither equal to zero nor to their conjugate signals. Overall, kv/kc was 0.62, and the correlation between kv and kc was not significantly different from zero. Similarly, in the oculomotor nucleus, kv was significantly different from kc for a majority of the cells. A few units had kv values less than or equal to zero, whereas other cells had very high kv values. Overall, the kv/kc for oculomotor units was nearly unity (0.94), and the correlation between kv and kc was 0.31. These results confirm previous reports that most neurons in the abducens and oculomotor nuclei with a horizontal eye position sensitivity carry both conjugate and vergence eye movement signals. We do not find that the relative magnitudes of these signals are closely matched for most neurons. It is more likely that vergence and conjugate signals are matched globally, for an entire nucleus, rather than for individual motoneurons. This view is consistent with the hypothesis that conjugate and vergence signals are generated independently and combined for the first time at the motoneurons. Our results also imply that some motoneurons play a more important role than others in either vergence or conjugate movements.

Abducens Nerve↗
PubMed1980

Saccades are spatially, not retinocentrically, coded.

Most models of the saccadic eye movement system imply that saccades are programmed for a certain distance and direction. Electrical stimulation of the brain was used to move the eyes of monkeys just before saccades to visual targets. Despite the stimulation-induced perturbation, saccades brought gaze to the target locations. This compensation indicates that saccades are coded to direct the eyes to a certain position in the orbit (or in space).

Animals↗
PubMed1980

Movement fields of saccade-related burst neurons in the monkey superior colliculus.

The presaccadic burst of superior colliculus (SC) neurons was examined in detail to determine whether or not information concerning the vector components (amplitude and direction) of a saccade is contained within the burst. Results indicate that the pattern of spike activity originating from a single saccade-related burst neuron in the SC does not encode saccade direction or amplitude. Identical discharges may precede a wide range of saccades. Neither the magnitude, configuration nor timing of the discharge are related in any unique way to the duration of the saccade alone or the amplitude of the saccade alone. Furthermore, it is unlikely that information concerning saccade amplitude or direction is encoded by different types of signals originating from different SC neurons. For different neurons, there is no consistent relationship between the parameters of the burst and the optimal saccade amplitude or direction. It is suggested that the discharge of saccade-related burst neurons of the SC serves as a trigger input to pontine circuitry generating the required saccadic burst signals. Information concerning saccade direction and amplitude is not contained within the trigger signal, but must be extracted from the spatial distribution of SC activity.

Animals↗
PubMed1980

Dissociation of visual and saccade-related responses in superior colliculus neurons.

1. Single-unit activity was recorded from the superior colliculus (SC) of monkeys trained to look to visual targets presented on an oscilloscope screen. On one task, target localization required that information concerning the retinal position of the target be combined with information concerning current or future eye position. This task also permitted a dissociation between the site of retinal stimulation and the metrics of the saccade triggered by the stimulation. 2. Vigorous visual responses of superficial SC neurons may occur that do not result in the activation of underlying saccade-related cells. The activity of these neurons signals the occurrence of a visual stimulus, whether or not the stimulus is selected for foveal viewing. 3. Saccade-related (SR) discharges of most intermediate and deep-layer SC neurons precede saccades with particular vectors, regardless of the region of retinal activation initiating the saccade. The discharge of these neurons is tightly coupled to saccade onset, even if changes in eye position have occurred since target appearance. Thus, the discharge of these SR neurons must occur after retinal error and eye-position signals have been combined to compute the necessary saccade vector. For most SR neurons, direct retinal activation of overlying visual neurons had no effect on either the vigor or probability of a SR discharge. The discharge of overlying visual cells is neither necessary nor sufficient to activate most SR cells. 4. The discharge of some SR cells is dependent on prior activation of overlying visual cells. Of 53 SR cells, only 3 were completely dependent on visual stimulation, while another 8 discharged less vigorously if corresponding visual activation failed to occur. 5. About one-quarter of the SR cells showed long-lead preburst activity. This activation was characterized by a low level of firing, which began after the saccade signal and continued until a saccade-linked burst occurred. 6. Cells were isolated that were visually responsive yet discharged prior to saccades in the absence of appropriate retinal stimulation. No component of the discharge of these quasi-visual (QV) cells appeared to be motor in the usual sense. The activity of these neurons appears to reflect eye-position error (the difference between actual and desired eye position) and to hold this information in spatial register until a saccade occurs or is cancelled. 7. It is concluded that the presumed linkage, implied in earlier versions of the foveation hypothesis, between the superficial layers (receiving direct retinal inputs) and the deeper layers of the SC is not necessary for the activation of SR neurons. Results suggest that the SC must generate or receive a signal that combines retinal error and eye-position information. These findings are discussed in terms of current models of the saccadic-control system.

Animals↗