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L E Mays

Publications and source records attributed to L E Mays.

At least 19 recordsLinked to original sources
PubMed2003

Pontine omnipause activity during conjugate and disconjugate eye movements in macaques.

Previous reports have shown that saccades executed during vergence eye movements are often slower and longer than conjugate saccades. Lesions in the nucleus raphe interpositus, where pontine omnipause neurons (OPNs) are located, were also shown to result in slower and longer saccades. If vergence transiently suppresses the activity of the OPNs just before a saccade, then reduced presaccadic activity might mimic the behavioral effects of a lesion. To test this hypothesis, 64 OPNs were recorded from 7 alert rhesus monkeys during smooth vergence and saccades with and without vergence. The firing rate of many OPNs was modulated by static vergence angle but not by version and showed transient changes during slow vergence without saccades. This modulation was smooth, and not the abrupt pause seen for saccades, indicating that OPNs do not act as gates for vergence commands. We confirmed that saccades made during both convergence and divergence are significantly slower and longer than conjugate saccades. OPNs paused for all saccades, and the pause lead (interval between pause onset and saccadic onset) was significantly longer for saccades with convergence, in agreement with our hypothesis. Contrary to our hypothesis, pause lead was not longer for saccades with divergence, even though these saccades were slowed as much as those occurring during convergence. Furthermore, there was no significant correlation, on a trial-by-trial basis, between pause lead and saccadic slowing. These results suggest that it is unlikely that presaccadic slowing of OPNs is responsible for the slower saccades seen during vergence movements.

Animals↗
PubMed1998

Serotonergic modulation of eye blinks in cat and monkey.

Serotonergic modulation of spontaneous and reflexive blinking was studied in four cats and one monkey. In cats, facial nucleus injections of the type-2 serotonin receptor (5-HT2) antagonist ketanserin tended to increase the latency of the first (R1) and second (R2) components of the blink reflex to supraorbital nerve stimulation. Injections of serotonin tended to increase and of ketanserin, to decrease the duration and amplitude of R2. Serotonin also produced unilateral blepharospasm and hemifacial spasm. In the monkey, the 5-HT2 agonist 2,5-dimethoxy-4-iodoamphetamine increased spontaneous blink frequency while ketanserin decreased both peak blink velocity and spontaneous blink frequency. These findings in cat and monkey indicate that serotonergic innervation of the facial nucleus has a behaviorally important role in modulation of spontaneous and reflexive blinks and suggest that dysfunction of serotonergic systems could be important to the pathophysiology of some cases of blepharospasm.

Animals↗
PubMed1995

Neuronal circuitry controlling the near response.

Experiments in primates have contributed greatly to our understanding of the neural mechanisms involved in the eye movements required to view objects at different distances. Early work focused on the circuitry for generating horizontal vergence eye movements alone. However, vergence eye movements are associated with lens accommodation and are usually accompanied by saccadic eye movements, so more recent work has been directed at understanding the interactions between vergence and accommodation, and between vergence and saccades. A new model explains the neural basis for interactions between vergence and accommodation by a neural network in which pre-motor elements are shared by these two systems. The effects of saccades on vergence eye movements appear to be the result of shared pre-motor circuits as well. Current evidence suggests that pontine omnipause neurons, known to be crucial for the generation of saccades, play an important role in the vergence pre-motor circuitry.

Accommodation, Ocular↗
PubMed1995

Neurons in monkey parietal area LIP are tuned for eye-movement parameters in three-dimensional space.

1. A functional class of neurons in area LIP on the lateral bank of the intraparietal sulcus were shown previously (Gnadt and Andersen 1988) to be related to the metrics of saccadic eye movements. In this study, we tested LIP neurons at different depths with respect to the plane of fixation. 2. Sixty-one neurons were identified for their increased activity before saccadic eye movements. While holding the location of the target constant at the center of the frontoparallel (saccadic) response field, the neurons were tested systematically during eye movements to target positions proximal (near) to the plane of fixation, at the plane of fixation, and distal (far) to the plane of fixation. By necessity, the movements of these targets required a combination of saccadic and vergence movements. 3. Seventy-two percent of the neurons were found to change their activity as a function of target depth relative to the plane of fixation. The neurons had broad tuning curves for depth. Some cells preferred "near" target positions, some preferred "far" positions, and others responded best in the frontoparallel plane of fixation. 4. The location of a neuron's response field in the frontoparallel plane remained constant regardless of target depth. However, the magnitude of the neuron's response increased when the target was positioned at the preferred depth and it decreased for targets positioned at nonpreferred depths. This indicated that the neurons always were related to the same frontoparallel coordinates, but responded more vigorously when the target was positioned at its preferred depth. 5. The visual display apparatus allowed independent presentation of two stimulus cues for depth: binocular disparity and accommodative demand whereas other cues were held constant. For many neurons, either cue was sufficient to tune the activity in depth, though most neurons responded best for the geometrically appropriate combination of the two cues. 6. Comparison of the binocular tuning for depth with the individual monocular responses showed that the tuning for depth was not produced by simple linear combination of two monocular response fields. 7. We tested a subset of the neurons in a double-movement task that dissociated the retinal coordinates of the visual stimuli from the eye-movement coordinates of the second movement. These tests confirmed earlier findings that this functional class of neurons are active when the eye-movement coordinates matched the neurons' response field. It was not necessary for a visual stimulus to fall within the neurons' response field for them to become active.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Electrical stimulation of the pontine omnipause area inhibits eye blink.

BACKGROUND: Single-unit recordings of pontine omnipause neurons (OPN) in the monkey have shown that these neurons cease firing for saccades in all directions. OPNs are located in pontine nucleus raphe' interpositus and are known to inhibit a variety of target neurons, including saccadic burst neurons. Recently, a single-unit investigation of these same OPNs revealed that they pause for blinks as well as saccades. Electrical microstimulation of the OPN area has been shown to inhibit saccadic eye movements in all directions. The present study is designed to determine if OPN area microstimulation inhibits blinks as well as saccades. METHODS: Two rhesus monkeys were trained to track visual targets for a reward. Eye and lid position were measured using the electromagnetic search coil technique. The pontine OPN area was located using single-unit recording and microstimulation techniques. OPN stimulation was delivered just before and during the presentation of air puffs to elicit blinks. RESULTS: OPN are microstimulation inhibited air puff-induced blinks as well as saccades. The threshold current for inhibiting blinks was generally slightly higher than for inhibiting saccades. CONCLUSIONS: Although OPN area stimulation inhibits blinks as well as saccades, the mechanisms for inhibiting these behaviors appears to be different. OPNs are known to inhibit saccadic burst neurons, but there is no evidence that these neurons inhibit orbicularis oculi motoneurons which burst for blinks. Moreover, the temporal pattern of OPN activity makes it unlikely that they directly suppress blinks. The OPN region appears to be important for eye retraction during blinks and may be associated with other pontine areas which control blinks.

Animals↗
PubMed1994

Characteristics of antidromically identified oculomotor internuclear neurons during vergence and versional eye movements.

1. Previous studies have shown that midbrain near response cells that increase their activity during convergent eye movements project to medial rectus motoneurons, which also increase their activity during convergence. Most neurons in the abducens nucleus decrease their firing rate during convergence, and the source of this vergence signal is unknown. Oculomotor internuclear neurons (OINs) in monkeys project primarily from the medial rectus subdivisions of the oculomotor nucleus to the contralateral abducens nucleus, although there is a smaller ipsilateral projection as well. Because of these anatomic connections, it has been suggested that the OIN input may be responsible for the vergence signal seen on abducens neurons. The behavior of the OINs during eye movements and their synaptic drive are not known. Thus the goal of this study is to determine the behavior of these neurons during conjugate and disjunctive eye movements and to determine if these neurons have an excitatory or inhibitory drive on the abducens neurons. 2. Single-unit recording studies in alert rhesus monkeys were used to characterize the behavior of OINs. Eighteen OINs were identified by antidromic activation and collision testing. The recorded OINs displayed a burst-tonic pattern of activity during adducting saccades, and the majority of these cells displayed an increase in tonic activity with convergent eye movements. 3. Identified OINs were compared with a large sample of non-activated and untested horizontal burst-tonic cells in the medial rectus subdivisions of the oculomotor nucleus. The results indicate that the OINs behave similarly to medial rectus motoneurons during vergence and versional eye movements. None of the OINs displayed vertical eye position sensitivity. 4. Microstimulation of the oculomotor nucleus where both the OINs and medial rectus motoneurons were located resulted in a large adducting twitch of the ipsilateral eye and a smaller abducting twitch of the contralateral eye. The latter effect was presumed to be the result of OIN innervation of the contralateral abducens nucleus. This result suggests that the crossed OIN pathway is predominately, if not entirely, excitatory. 5. Injection of 10% lidocaine HCl into the medial rectus subdivision of the oculomotor nucleus caused a reversible inactivation of the medial rectus motoneurons and OINs. As expected, the inactivation of medial rectus motoneurons resulted in an exophoria and weakness of adduction for the eye ipsilateral to the lidocaine injection. In addition, the lidocaine injection resulted in hypometric and slowed abducting saccades in the eye contralateral to the injection site. This result also suggest that the crossed OIN pathway is excitatory.(ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve↗
PubMed1994

Behavior of identified Edinger-Westphal neurons during ocular accommodation.

1. The present study used single-unit recording and antidromic activation techniques in alert rhesus monkeys to examine the static and dynamic behavior of 21 parasympathetic, preganglionic neurons of the Edinger-Westphal nucleus (EW) during ocular accommodation. 2. All identified EW neurons were active when viewing at optical infinity with an average firing rate of 11.6 spikes/s. During near viewing, there was a linear relationship between firing rate and accommodation with an overall gain for the population of preganglionic EW neurons of 3.3 (spikes/s)/diopter. 3. The activity of eight identified EW neurons was studied during viewing of targets with conflicting vergence and accommodative demands to dissociate their vergence and accommodation responses. With normal viewing these responses are so closely matched that it cannot be determined if the activity of a cell is related to vergence or to accommodation, but with dissociated viewing these relationships can be determined. Under this viewing condition, six preganglionic EW neurons showed the same relationship to accommodation as they did during normal viewing. However, the activity of two cells could not be explained solely by accommodation, and they showed some activity related to vergence. 4. Microstimulation at the sites of identified EW neurons produced accommodation in the ipsilateral eye. Repeated measures of the effect of microstimulation yielded a value of 75 ms for the latency of the response. This latency was essentially the same in both animals tested. 5. The activity of identified EW neurons is related to the velocity of accommodation as well as to static accommodation. The relationship between accommodation velocity and firing rate was studied for 15 identified EW neurons during sine-wave tracking of targets moving in depth. All of these cells showed a clear relationship between firing rate and accommodation velocity. Overall, this group of identified EW neurons showed a velocity sensitivity of 1.2 (spikes/s)/(diopter/s) and an estimated neural time constant of 380 ms. 6. Eleven neurons encountered near to preganglionic EW neurons could not be antidromically activated by stimulation of the oculomotor nerve. These neurons had statistically higher gains with respect to the near response; indeed, there was no overlap between the gains of these neurons and the gains of preganglionic EW neurons. Upon dissociation of vergence from accommodation, they were found to be related to either vergence or to vergence and accommodation but not solely to accommodation.

Accommodation, Ocular↗
PubMed1992

Dynamic properties of medial rectus motoneurons during vergence eye movements.

1. An early study by Keller reported that medial rectus motoneurons display a step change in firing rate during accommodative vergence movements. However, a later study by Mays and Porter reported gradual changes in firing rate during symmetrical vergence movements. Furthermore, subsequent inspection of the activity of individual medial rectus motoneurons during vergence movements indicated transient changes in their firing rate that had not been noted by Mays and Porter. For conjugate eye movements, in addition to a position signal, motoneurons display an eye velocity signal that compensates for the characteristics of the oculomotor plant. This suggested that the transient change in firing rate seen during vergence movements represented a velocity signal. Therefore the present study used single-unit recording techniques in alert rhesus monkeys to examine the dynamic behavior of medial rectus motoneurons during vergence eye movements. 2. The relationship between firing rate and eye velocity was first studied for vergence responses to step changes in binocular disparity and accommodative demand. Inspection of single trials showed that medial rectus motoneurons display transient changes in firing rate during vergence eye movements. To better visualize the dynamic signal during vergence movements, an expected firing rate (eye position multiplied by position sensitivity of the cell plus its baseline firing rate) was subtracted from the actual firing rate to yield a difference firing rate, which was displayed along with the eye velocity trace for individual trials. During all smooth symmetrical vergence movements, the profile of the difference firing rate very closely resembled the velocity profile. 3. To quantify the relationship between eye velocity and firing rate, two approaches were taken. In one, peak eye velocity was plotted against the difference firing rate. This plot yielded a measure of the velocity sensitivity of the cell (prv). In the other, a scatter plot was produced in which horizontal eye velocity throughout the vergence eye movement was plotted against the difference firing rate. This plot yielded a second measure of the velocity sensitivity of the cell (rv). 4. The behavior of 10 cells was studied during both sinusoidal vergence tracking and conjugate smooth pursuit over a range of frequencies from 0.125 to 1.0 Hz. This enabled the frequency sensitivity of the medial rectus motoneurons to be assessed for both types of movements. Both vergence velocity sensitivity and smooth pursuit velocity sensitivity decreased with increasing frequency. This is similar to a finding by Fuchs and co-workers for lateral rectus motoneurons during smooth pursuit eye movements.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Characteristics of near response cells projecting to the oculomotor nucleus.

1. Previous work has shown neurons just dorsal and lateral to the oculomotor nucleus that increase their firing rate with increases in the angle of ocular convergence. It has been suggested that the output of these midbrain near response cells might provide the vergence command needed by the medial rectus motoneurons. However, lens accommodation ordinarily accompanies convergence, and a subsequent study showed that only about one-half of these midbrain near response cells carried a signal related exclusively to vergence. One hypothesis suggested by this finding is that this subgroup of neurons might have a unique role in providing a "pure" vergence signal to the medial rectus motoneurons. 2. In the present study extracellular recordings were made from midbrain near response cells in monkeys while eye position and lens accommodation were measured. The monkeys viewed targets through an optical system that allowed the accommodative and ocular vergence demands to be manipulated independently. This approach was used to produce a partial dissociation of accommodative and vergence responses, so that an accommodative and vergence coefficient could be determined for each cell, by the use of the following equation FR = R0 + kda x AR + kdv x CR where FR is the firing rate of the near response cell, R0 is the predicted firing rate for a distant target, kda is the (dissociated) accommodation coefficient, AR is the accommodative response, kdv is the (dissociated) vergence coefficient, and CR is the convergence response. 3. The vergence and accommodation coefficients were determined for a large number of midbrain near response cells, including a subset that could be antidromically activated from the medial rectus subdivisions of the oculomotor nucleus. Some near response neurons were found with signals related exclusively to convergence (i.e., kdv greater than 0 and kda = 0), whereas several others had signals related exclusively to lens accommodation (i.e., kda greater than 0 and kdv = 0). The majority of the near response cells had signals related to both responses (i.e., kda not equal to 0 and kdv not equal to 0). Furthermore, the vergence and accommodation coefficients of near response cells appeared to be continuously distributed. Some cells had negative accommodation or vergence coefficients. 4. The 17 near response cells that could be antidromically activated from the oculomotor nucleus presumably provide vergence signals to the medial rectus motoneurons. Although all had positive vergence coefficients, only four of these cells carried signals that were related exclusively to vergence.(ABSTRACT TRUNCATED AT 400 WORDS)

Accommodation, Ocular↗
PubMed1991

Antidromic identification of midbrain near response cells projecting to the oculomotor nucleus.

Medial rectus motoneurons carry both conjugate and vergence eye position signals. Abducens internuclear neurons, whose axons travel in the medial longitudinal fasciculus, provide these motoneurons with the major signal for conjugate eye movements but not for vergence eye movements. A vergence signal appropriate for these motoneurons is seen on the near response cells that are found in the mesencephalic reticular formation within 2 mm of the oculomotor nucleus. The goal of the present study was to determine if midbrain near response cells project to the medial rectus subdivision of the oculomotor nucleus. Near response cells were recorded in two trained rhesus monkeys with ocular search coils. A stimulating electrode was positioned within the medial rectus subdivision of the oculomotor nucleus. Twenty-eight near response cells were found that could be driven by single pulse microstimulation of the ipsilateral medial rectus subdivision. In all cases, antidromic activation was confirmed by collision testing. Attempts to antidromically activate midbrain near response cells from the contralateral medial rectus subdivision were unsuccessful. Most antidromically activated cells had a steady state firing rate proportional to vergence angle. One cell also showed burst activity during the vergence eye movements. Divergence cells were not antidromically activated.

Animals↗
PubMed1991

Trochlear unit activity during ocular convergence.

1. Ocular convergence is usually accompanied by excyclotorsion of the eyes. Furthermore, the magnitude of cyclotorsion is dependent on the elevation of the eyes. The reason for this excyclotorsion during convergence is not understood. 2. Excyclotorsion could be produced by either increased activity in the inferior oblique muscle or decreased activity in the superior oblique muscle. An earlier study indicated that convergence may also be accompanied by a temporal (lateral) translation of the eye. This observation is more consistent with a relaxation of the superior oblique than contraction of the inferior oblique. 3. This hypothesis was tested by recording the activity of 31 neurons in the trochlear nucleus, which contains the superior oblique motoneurons. This was done in alert monkeys that were trained to make both versional and vergence eye movements. In addition, the cyclotorsion associated with convergence was measured in one of these monkeys. 4. A consistent excyclotorsion associated with convergence was observed. Trochlear unit activity decreased during convergence in all cells tested. The magnitude of this decrease was significantly greater than that seen with conjugate adduction. Furthermore, the size of the decrease varied systematically with ocular elevation in a manner that was consistent with earlier measures of cyclotorsion during convergence. 5. These results suggest that the excyclotorsion seen during convergence, and perhaps the lateral translation of the eye, are due to a relaxation of the superior oblique muscle. This relaxation during convergence is greater than that which accompanies similar conjugate movements of the eyes. We hypothesize that this peculiar pattern of muscle innervation has a motor rather than sensory function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Signal transformations required for the generation of saccadic eye movements.

Chronic unit recording experiments conducted over the past two decades have identified many functional classes of neurons with saccade-related activity that reside in a host of brainstem nuclei. Older models of the saccadic system were based upon the properties of only a few of these functional types of neurons. They described the putative flow of signals through the brainstem circuitry and specified some, but not all, of the signal transformations to be performed. How the necessary computations were performed by neurons was not always explicit. Recent experiments investigating the neural control of saccadic eye movements and modifications of the original models are designed to fill in the details of the broad sketch of saccadic circuitry originally available. This review suggests one strategy for proceeding with this effort. Saccadic command signals observed in the SC require transformation to interface with the burst generators and motoneuron pools innervating the extraocular muscles. Specifying the signal transformations required for this interface should facilitate the design of experiments directed toward an understanding of the functional properties of cells located in nuclei intervening between the SC and the pulse/step circuitry, subsets of neurons that often have no role in models of the saccadic system. In this review, we hypothesize that neurons residing in various tectorecipient brainstem nuclei participate in one or more of the required signal transformations. The pathway from SC to cMRF and PPRF may be involved in the extraction of information about the amplitude and/or velocity of the horizontal component of oblique saccades. The pathway from SC to NRTP and cerebellar vermis may act selectively to generate signals compensating for the presaccadic orbital position. Finally, the activity of LLBNs and MLBs discharging maximally before oblique saccades may form the basis of computations required to match component velocity with overall saccade direction and amplitude. Although the data supporting these speculations are meager at present, such conjectures do form the basis of working hypotheses that can be tested experimentally. We also considered the implications of kinematic constraints, especially Donders' and Listing's laws, for future investigations. Tweed & Vilis (1987, 1990) proposed models specifically designed to handle these constraints. In their models, eye position is represented on four oculomotor channels: three coding the vector components of eye position, and one carrying a signal inversely related to gaze eccentricity and torsion. Yet, other evidence suggest that simpler computations may suffice for the implementation of laws that are only approximately obeyed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Abducens internuclear neurons carry an inappropriate signal for ocular convergence.

1. Single-unit recording studies in alert Rhesus monkeys characterized the vergence signal carried by abducens internuclear neurons. These cells were identified by antidromic activation and the collision of spontaneous with antidromic action potentials. The behavior of abducens internuclear neurons during vergence was compared with that of horizontal burst-tonic fibers in the medial longitudinal fasciculus (MLF) and to that of a large sample of unidentified abducens cells (presumably both motoneurons and internuclear neurons). 2. The results indicate that abducens internuclear neurons and lateral rectus motoneurons behave similarly during vergence eye movements: the majority of both groups of cells decrease their firing rate for convergence eye movements: a minority show no change for vergence. This finding is strongly supported by recordings of horizontal burst-tonic fibers in the MLF, the majority of which decrease their activity significantly for convergence eye movements. 3. These findings indicate that a net inappropriate vergence signal is sent to medial rectus motoneurons via the abducens internuclear pathway. Because medial rectus motoneurons increase their activity appropriately during symmetrical convergence, this inappropriate MLF signal must be overcome by a more potent direct vergence input. 4. Overall, both abducens internuclear neurons and lateral rectus motoneurons decrease their activity for convergence less than would be expected based on their conjugate gain. This implies that some degree of co-contraction of the lateral and medial rectus muscles occurs during convergence eye movements. 5. Some horizontal burst-tonic MLF fibers decrease their activity more for convergence than any recorded abducens neuron. These fibers may arise from cells in the nucleus prepositus hypoglossi or vestibular nuclei.

Abducens Nerve↗
PubMed1989

Lidocaine-induced unilateral internuclear ophthalmoplegia: effects on convergence and conjugate eye movements.

1. To characterize the vergence signal carried by the medial longitudinal fasciculus (MLF), it was subjected to reversible blockade by small injections of 10% lidocaine hydrochloride. The effects of these blockades on both conjugate and vergence eye movements were studied. 2. With this procedure, experimentally induced internuclear ophthalmoplegia (INO) and its effects on conjugate eye movements could be studied acutely, without possible contamination from long-term oculomotor adaptation. In the eye contralateral to the MLF blockade, saccadic and horizontal smooth-pursuit eye movements were normal. Horizontal abducting nystagmus, often seen in patients with INO, was not observed in this eye. 3. As previously reported for INO, profound oculomotor deficits were seen in the eye ipsilateral to the MLF blockade. During maximal blockade, adducting saccades and horizontal smooth-pursuit movements in this eye did not cross the midline. Adducting saccades were reduced in amplitude and peak velocity and showed significantly increased durations. Abducting saccades, which were slightly hypometric, displayed a marked postsaccadic centripetal drift. 4. The eye ipsilateral to the blockade displayed a pronounced, upward, slow drift, whereas the eye contralateral to the blockade showed virtually no drift. Furthermore, although vertical saccades to visual targets remained essentially conjugate, the size of the resetting quick phases in each eye was related to the amplitude of the slow phase movement in that eye. Thus the eye on the affected side displayed large quick phases, whereas the eye on the unaffected side showed only slight movements. On occasion, unilateral downbeating nystagmus was seen. This strongly suggests that the vertical saccade generators for the two eyes can act independently. 5. The effect of MLF blockade on the vergence gain of the eye on the affected side was investigated. As a measure of open-loop vergence gain, the relationship of accommodative convergence to accommodation (AC/A) was measured before, during, and after reversible lidocaine block of the MLF. After taking conjugate deficits into account, the net vergence signal to the eye ipsilateral to the injection was found to increase significantly during the reversible blockade. 6. The most parsimonious explanation for this increased vergence signal is suggested by the accompanying single-unit study. This study showed that abducens internuclear neurons, whose axons course in the MLF, provide medial rectus motoneurons with an appropriate horizontal conjugate eye position signal but an inappropriate vergence signal. Ordinarily, this incorrect vergence signal is overcome by another, more potent, v

Animals↗
PubMed1988

Purkinje cell activity in rats following chronic treatment with harmaline.

Harmaline and related alkaloids produce a fine, generalized motor tremor with a frequency of 8-14 Hz in many mammalian species. The tremor is though to be initiated by the synchronous activation of cells in the inferior olive. Repeated administration of the drug at tremorogenic doses results in the rapid development of tolerance in the rat. Since the generation of cerebellar cyclic 3',5'-guanosine monophosphate by harmaline or apomorphine is reduced in harmaline-tolerant rats, it is possible that the site of tolerance is the olivocerebellar system. The present study used extracellular single unit recording techniques to determine whether harmaline tolerance was associated with changes in the firing patterns of Purkinje cells in the cerebellar vermis of the rat. In non-tolerant animals, the majority (8/13) of Purkinje cells recorded in the vermis responded to harmaline with a rhythmic increase in complex spike rate and a prolonged suppression of simple spikes. In harmaline-tolerant animals, only one cell in 14 could be identified that showed this response. In these animals, a variety of responses not encountered in experimentally naive animals were observed. Since the complex spike activity of Purkinje cells is presumed to reflect the activity of climbing fibers originating in the cells of the inferior olive, the results of the studies reported here support the conclusion that a reduction in the synchronous activation of cells at the olivocerebellar level blocks the appearance of tremor in harmaline-tolerant animals.

Action Potentials↗
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↗