PubMed Health⌕ Search

Biomedical subjects

T J Ebner

Publications and source records attributed to T J Ebner.

At least 55 records · Page 3Linked to original sources

Acute effects of levodopa on wrist movement in Parkinson's disease. Kinematics, volitional EMG modulation and reflex amplitude modulation.

Acute changes in motor performance due to levodopa were evaluated by a series of four motor tests unified by their focus on wrist flexion-extension movements. Subjects with idiopathic Parkinson's disease were evaluated with this battery of tests before (OFF) and after their usual morning dose of levodopa (ON). The test battery consisted of (i) repetitive self-paced movement in which velocity was to be maximized; (ii) visually guided tracking of a sinusoid and a square wave; and (iii) an assay of stretch reflex modulation during volitional sinusoidal tracking. The maximal wrist joint velocity of self-paced reciprocating flexion and extension movements increased after levodopa (ON), without significant changes in the movement period or amplitude. In the two tracking tasks, some subjects improved as evident by a lower root mean square (rms) error, but in similar numbers of subjects the rms error increased. Overall, the rms error, peak velocity or peak movement amplitude did not change after levodopa in either tracking task. Significant and consistent changes did occur after levodopa in an assay of reflex modulation during error-constrained tracking (Johnson et al., Brain 1991; 114: 443-60). The amplitude of volitional EMG increased after levodopa, with a concurrent reduction in reflex EMG. These changes are consistent with the noted increase in movement velocity. These results show that the effects of levodopa on movement velocity were not consistently translated into increased accuracy. The changes in the long latency reflex gain argue for a central control of this reflex, mediated by structures sensitive to levodopa. Finally, the results show that the quantitative evaluation of levodopa therapy cannot be unidimensional, but requires a battery of motor tests as undertaken in this study.

Aged↗

Purkinje cell complex spike activity during voluntary motor learning: relationship to kinematics.

1. We examined the relationship of cerebellar Purkinje cell discharge to the scaling of kinematics during a voluntary motor learning paradigm. The study focused on whether the occurrence of complex spike (CS) discharge was associated with kinematic changes. Two primates (Macaca mulatta) were trained to move a cursor using a two-joint manipulandum over a horizontal video screen from a start target to one of four target boxes. The relationship between the cursor and the hand (gain) was changed, requiring scaling of movement distance to complete the task. As previously described, when the novel gain was presented over 100-200 movement trials the animals adapted their movements by using a strategy of scaling the amplitude and velocity of the first phase of the movement while keeping time to peak velocity constant. 2. The paradigm consisted of four different phases. A control phase at a gain of 1.0 was initially performed. The learning phase over the next 180-210 movements used one of four gains (0.6, 0.75, 1.5, or 2.0). Last, a testing phase involved 80% of 100 trials at the learned gain and 20% of the trials at the control gain of 1.0. The distance control phase consisted of using a gain of 1.0 but having the animal move to targets placed at the distance and direction the hand moved in the adapted state. 3. Simple spikes (SSs) and CSs of 141 Purkinje cells recorded primarily in the intermediate and lateral regions of zones V and VI in three cerebellar hemispheres from the two primates were recorded during the distance control, control, learning, and testing phases. Some cells were recorded in lobule VII and Crus I. CS activity increased during the learning phase, as documented previously. The increase in CS discharge occurred before or during the first 200-300 ms of the movement. This is the same time period in which the kinematic changes necessary for adaptation to the novel gain occur. Of 141 Purkinje cells recorded during the learning paradigm, 104 (74%) demonstrated significant increases in CS firing rate during the learning-testing phase. Of these 104 cells, 82 had statistically significant SS modulation. 4. Movement trials with CSs were separated from the trials without CSs. Aligning the kinematic and spike train data on movement onset, the average velocity profiles were subtracted from each other and a strict statistical criterion applied to test for the significance of any differences. Movement trials randomly sorted into two groups served as a control.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Distance- and error-related discharge of cells in premotor cortex of rhesus monkeys.

Previous work on the premotor cortex has emphasized its role in preparation for movement. In this study, we concentrated on the activity that occurs during a movement, particularly when the required movement amplitude is unexpectedly changed by introduction of a visuo-spatial error. In two rhesus monkeys, discharge of premotor neurons was recorded during a multi-joint reaching movement. Units could be divided into two categories: (1) those whose discharge monotonically increased or decreased with movement amplitude; and (2) those whose discharge was modulated with the unexpected change in amplitude but not monotonically. We suggest that the latter class of cells may be detecting or responding to a visuo-motor error. Thus, the premotor cortex is not only involved in preparation but plays a role in the ongoing control of movement execution.

Animals↗

Independent control of reflex and volitional EMG modulation during sinusoidal pursuit tracking in humans.

It is well known that during volitional sinusoidal tracking the long-latency reflex modulates in parallel with the volitional EMG activity. In this study, a series of experiments are reported demonstrating several conditions in which an uncoupling of reflex from volitional activity occurs. The paradigm consists of a visually guided task in which the subject tracked a sinusoid with the wrist. The movement was perturbed by constant torque or controlled velocity perturbations at 45 degrees intervals of the tracking phase. Volitional and reflex-evoked EMG and wrist displacement as functions of the tracking phase were recorded. The relationship of both short-latency (30-60 ms) and longer-latency (60-100 ms) reflex components to the volitional EMG was evaluated. In reflex tracking, the peak reflex amplitude occurs at phases of tracking which correspond to a maximum of wrist joint angular velocity in the direction of homonymous muscle shortening and a minimum of wrist compliance. Uncoupling of the reflex and volitional EMG was observed in three situations. First, during passive movement of the wrist through the sinusoidal tracking cycle perturbation-evoked long-latency stretch reflex peak is modulated as for normal, volitional tracking. However, with passive joint movement the volitional EMG modulation is undetectable. Second, a subset of subjects demonstrate a normally modulated and positioned long-latency reflex with a single peak. However, these subjects have distinct bimodal peaks of volitional EMG. Third, the imposition of an anti-elastic load (positive position feedback) shifts the volitional EMG envelope by as much as 180 degrees along the tracking phase when compared with conventional elastic loading. Yet the long-latency reflex peak remains at its usual phase in the tracking cycle, corresponding to the maximal velocity in the direction of muscle shortening. Furthermore, comparison of the results from elastic and anti-elastic loads reveals a dissociation of short- and long-latency reflex activity, with the short-latency reflex shifting with the volitional EMG envelope. Comparable results were also obtained for controlled velocity perturbations used to control for changes in joint compliance. The uncoupling of the reflex and volitional EMG activity in the present series of experiments points to a flexible relationship between reflex and volitional control systems, altered by peripheral input and external load.

Adult↗

Optical imaging of parallel fiber activation in the rat cerebellar cortex: spatial effects of excitatory amino acids.

Using optical imaging, the effects of excitatory amino acids and their antagonists on the spatial pattern of activity evoked by the stimulation of parallel fibers in the cerebellar cortex of the anesthetized rat were examined. A vermal folium was stained with the stryrl voltage-sensitive dye RH-795 and imaged with a cooled charge-coupled service system during the activation of the parallel fibers with surface stimulation. Stimulation of the cerebellar cortex produced discrete "beams" of optical activity consistent with extracellular field recordings. The signal-to-noise ratio was excellent (> 10:1), reducing the number of stimuli, exposure time, and acquisition time needed to produce images. Extracellular field potential recordings were used to assay neuronal activity as well as the effects of the various excitatory amino acid agonists. Application of several glutamate receptor antagonists reversibly blocked the optical signals as well as the synaptic components of the extracellular field potentials. Neither N-methyl-D-aspartate nor its antagonist, (+/-)-2-amino-7-phosphonoheptanoic acid, had any affect on the optical signals or field potentials. These results indicate that the optical signal is not due to the evoked parallel fiber activity, but is generated mainly by postsynaptic targets and the parallel fiber synaptic action is primarily mediated by non-N-methyl-D-aspartate receptors. Other excitatory amino acid agonists had a differential effect on the optical response. Glutamate and kainate increased the "on beam" optical signal evoked by parallel fiber stimulation, in amplitude and width. In contrast, quisqualate always decreased the amplitude and width of the optical beam. Also, quisqualate produced an increase in fluorescence lateral to the optical beam, possibly due to an increase in "off beam" inhibitory activity. The changes in the extracellular field potentials were in agreement with the effects on the optical signals. Two possible mechanisms are proposed to account for the inhibitory effect of quisqualate. One is that quisqualate desensitizes Purkinje cell receptors, the other is that inhibitory interneurons in the cerebellar cortex are more preferentially excited with quisqualate application which in turn inhibits Purkinje cells both "on beam" and "off beam". In conclusion, voltage-sensitive dye optical signals evoked by stimulation of the cerebellar surface were imaged at high signal-to-noise levels using a cooled charge-coupled device system. Use of excitatory amino acid agonists and antagonists demonstrated that the optical signal was dependent on postsynaptic activity and confirmed that the parallel fiber postsynaptic action is primarily mediated by non-N-methyl-D-aspartate receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Neuronal specification of direction and distance during reaching movements in the superior precentral premotor area and primary motor cortex of monkeys.

1. Single-unit neuronal activity was recorded in the primary motor and superior precentral premotor areas of two rhesus monkeys during an arm reaching task. The task involved moving a cursor displayed on a video terminal using a draftsman's arm-type manipulandum. From a centrally located start box the animal was required to move to 1 of 48 target boxes at eight different directions (0-360 degrees in 45 degrees intervals) and six distances (1.4-5.4 cm in 0.8-cm increments). Both direction and distance for the upcoming movement were unpredictable. 2. The activity of 197 arm movement-related cells was recorded and evaluated for each of the 48 targets. Histological examination showed the cells to be primarily in the primary motor cortex or in the premotor area around the superior precentral sulcus. Each cell's discharge was aligned on movement onset and averaged over five trials for each target. Movement kinematics including hand path velocity were also determined. The task time was divided into three epochs, a premovement period (PT), a movement period (MT), and total time (TT = PT+MT). For each epoch the average firing was correlated with the direction and distance of the movement using various regression procedures. 3. An analysis of variance (ANOVA) showed that the majority of neurons were modulated significantly by movement direction in each of the three time periods, PT (73.7%), MT (68.3%), and TT (78.5%). The relationship of the firing to direction was fit to a cosine tuning function for each significantly modulated cell. In 86.3% of the cells the firing was correlated significantly with a cosine function of movement direction in TT. A cell's preferred direction varied little for different movement distances. The mean difference in preferred direction for the smallest possible change in distance (0.8 cm) was 12.8 +/- 11.4 degrees (SD) and 17.1 +/- 14.7 degrees for the largest change in distance (4.0 cm). 4. Correlation analysis revealed that the activity of the majority of cells was modulated significantly by distance along at least one direction in each of the three time periods, PT (46.8%), MT (68.8%), and TT (67.7%). Subsequently, a univariate linear regression model was used to quantify a cell's discharge as a function of distance. For the regressions of firing with distance with a statistically significant correlation (r > 0.8), the mean slope was 3.59 +/- 0.17 spikes.s-1.cm-1 for the total time. The existence of a significant distance modulation was not invariably correlated with a cell's preferred movement direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Deblurring of 3-dimensional patterns of evoked rat cerebellar cortical activity: a study using voltage-sensitive dyes and optical sectioning.

One of the benefits of imaging neuronal activity is the capability of resolving spatial patterns in the x-y plane. With optical sectioning microscopy, the 3-dimensional (3-D) structure may also be studied without physical deformation by serially moving the focal plane of the microscope through the volume of interest along the focal axis. However, each image is blurred by contributions from neighboring planes. This degradation is most severe for low numerical aperture lenses and large amounts of defocus. In this study, an image restoration method using the optical properties of an aberration-free, defocused optical system has been developed for improving optical signals from voltage-sensitive dyes. Deblurring based on the optical transfer function (OTF) of the system was applied on two test sets of serially sectioned images: (1) fluorescent beads and (2) in vivo rat cerebellar cortex stained with the voltage-sensitive dye RH795. This method was shown to reduce significantly the out-of-focus contribution to the images, improving the spatial resolution not only in the x-y plane, but also the z axis. The algorithms were then applied to optical signals obtained by stimulation of the cerebellar surface. Optical signals having a distinct beam-like pattern were evoked and recorded over depths ranging from 0 to 300 microns prior to deblurring. Application of the deblurring algorithm reduced the depth of cerebellar cortex over which the optical signals were observed. In agreement, field potential recordings of the evoked parallel fiber volley and post-synaptic components were restricted to a narrow range of depths similar to the deblurred optical images. Removal of out-of-focus information is an essential step in the serial sectioning of central nervous system structures for neuronal imaging and 3-D reconstruction.

Algorithms↗

Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced hemiparkinsonism on the kinematics of a two-dimensional,multijoint arm movement in the rhesus monkey.

The effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) on the kinematics of two-dimensional arm movements in the primate were studied. Two rhesus monkeys were trained to move a manipulandum at various distances and directions in horizontal space from a centrally located target box. Several kinematic parameters including reaction time, and time and amplitude of peak tangential velocity were analysed. Following an extensive control evaluation period, the animals were unilaterally injected with MPTP into the internal carotid artery. The animals were restudied for up to 289 days following induction of hemiparkinsonism. Larger-amplitude movements (greater than 3.5 cm) were more severely affected than smaller amplitude movements. Both animals exhibited marked changes in the arm movements including increased time-to-peak velocity and decreased peak velocity. The degree of the kinematic changes was spatially dependent, with the decrease in velocity as well as the time-to-peak velocity being more pronounced for the larger, outward movements. Reaction time increased but showed no spatial dependency. Kinematic deficits persisted over the entire time-period studied. Also, the kinematic changes were reduced by levo-3,4 dihydroxyphenylalanine in a dose-dependent manner. Tyrosine hydroxylase immunohistochemistry documented extensive cell loss in the substantia nigra. These results show that both the timing as well as the amplitude of the velocity profiles are disrupted by MPTP consistent with the known akinesia and bradykinesia of parkinsonism. Although abnormalities were present for all directions and distances, a spatial dependency to the deficits was detected. The observation of more pronounced changes for larger, outward movements suggests a role for the basal ganglia in production of larger-amplitude movements directed away from the body.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Purkinje cell complex and simple spike changes during a voluntary arm movement learning task in the monkey.

1. To evaluate the role of the cerebellum during improvement of voluntary motor performance over time, the discharge of 88 Purkinje cells in the intermediate and lateral cerebellum of two primates (Macaca mulatta) was investigated during a motor learning task involving visually guided arm movements. The animals were trained to move a draftsman's style manipulandum over a horizontally placed video screen. The animals were required to move a cursor from the start box to one of four target boxes by movement of the manipulandum. Errors were introduced into the movement by altering the visual feedback loop, changing the gain between the cursor movement and the hand movement. When a novel gain was presented over 100-200 movement trials, the animals adapted the movements to the new gain. The animals used a strategy of scaling the amplitude and velocity of the initial phase of the movement while keeping the time to peak velocity constant. 2. The learning paradigm consisted of an initial control phase with 35-100 trials at the gain of 1.0. The next 100-200 trials, the learning phase, were presented at one of four gains (0.6, 0.75, 1.5, 2.0). Lastly, a testing phase involved 80% of 100 trials at the learned gain and 20% of the trials randomly interspersed at the control gain of 1.0. An additional "distance control" was used in most experiments to control for the movement scaling associated with learning. In this series of movements using a gain of 1.0, the target box was placed at the distance and direction the hand would have to move in the adapted state. Two aspects of the kinematics were the same for the distance control and the movement at the learned gain: movement amplitude and time to peak velocity. There were, however, slight differences in the peak velocity attained. For gains < 1.0, the peak velocity of the learned task was 14-20% lower than the distance controls, and for gains > 1.0, it was 10-18% higher. 3. After implantation of chronic unit recording hardware, Purkinje cell simple and complex spike discharge was recorded extracellularly during the learning task. The cells were located primarily in the ipsilateral intermediate zone or nearby hemisphere of lobules V and VI. Simple and complex spike histograms, as well as averages of the hand displacement and velocity profiles, were calculated for each phase of the paradigm. To determine the time course of any changes, the learning trials were subdivided into three equal phases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

Sustained release of nerve growth factor from biodegradable polymer microspheres.

Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration.

Adrenal Medulla↗

Scaling of the metrics of visually-guided arm movements during motor learning in primates.

Hand trajectory, tangential velocity and acceleration, time and distance until peak velocity and reaction time were analyzed during the process of learning a skilled, visually-guided arm movement. Primates were trained to move a cursor with a manipulandum from a start box to target boxes displayed on a horizontal video screen during control conditions and when the relationship (gain) between the cursor and manipulandum was altered. The animals adapted to the altered feedback over 100-200 trials. A subsequent testing phase with randomly interspersed trials using the control gain demonstrated that the animals had modified their movements appropriately for the novel gain. Examination of the kinematics revealed that in adapting to a novel gain, primates scaled movement amplitude, tangential velocity, acceleration, and duration appropriately for the distance the hand needed to travel. Yet time to peak velocity was kept constant. Reaction time also remained unchanged for three of the four animals. Movements were performed in two phases, the first from movement onset to peak velocity and the second from peak velocity until the end of the movement. During the first phase the shape of the trajectory and velocity profile were stereotypic and without evidence of any corrections, consistent with this phase being essentially open loop. However, corrections occurred in the second phase and we propose visual feedback was used to correct for the difference in hand/cursor position. Learning appeared to involve utilizing the errors from previous trials to modify the early feedforward phase of subsequent trials. Peak tangential velocity, total movement duration and distance reached at peak tangential velocity all scaled linearly with the total movement distance required at each gain. Based on regression analyses, for none of these variables were the changes in learning completely adequate to compensate for total distance required. However, distance to peak velocity scaled with peak velocity in relation to the control gain. The results show that non-human primates adopt a consistent strategy when learning to scale a multi-joint movement. The metrics of the movement scaled yet the time to peak velocity remained constant, suggesting independent control of time and amplitude. Keeping time to peak velocity constant as well as the scaling of peak velocity with distance to peak velocity are viewed as ways to simplify the learning process.

Animals↗

Modulation of the stretch reflex during volitional sinusoidal tracking in Parkinson's disease.

Sinusoidal visually-guided wrist tracking, in normal and parkinsonian subjects, was perturbed by torque transients every 90 degrees throughout the movement. Long-latency stretch reflex and volitional EMG amplitude modulations were assessed as functions of the tracking phase. Reflex modulation during tracking, both in wrist flexor and extensor muscles, was found to differ significantly between parkinsonian and normal subjects. In the parkinsonian group, the abnormality consisted of an increased reflex activity during tracking phases in which the muscle was lengthening. At these phases the reflex generated torque is opposite in direction to the volitionally generated torque and the tracking movement. No differences in the unperturbed volitional EMG modulation were observed between groups for this error constrained tracking paradigm. Significant correlations were found between ratings of bradykinesia and the amount of abnormal reflex modulation in the wrist flexor. These data suggest that a component of bradykinesia results from a defective coordination of supraspinal reflex and volitional control systems.

Aged↗

Lesioning of the striatum reverses motor asymmetry in the 6-hydroxydopamine rodent model of parkinsonism.

In the rat several paradigms of grafting of adrenal medulla into the striatum were studied following the induction of a parkinsonian model, using a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. Direct autologous grafting of adrenal medulla into the caudate-putamen complex, a radiofrequency lesion of the striatum alone, and a radiofrequency lesion followed by delayed grafting of adrenal medulla were compared by analyzing rotational behavior. Direct grafting of adrenal medulla produced an overall reduction in apomorphine induced turning behavior by 43.5% when compared with controls. Radiofrequency lesioning of the striatum without graft showed the best improvement over control animals with a 92% reduction in the total number of rotations induced by apomorphine. Delayed grafting into the caudate lesion cavity also produced a dramatic reduction in motor asymmetry but did not improve the behavioral outcome over that of the lesion alone. Animals receiving only radiofrequency lesions exhibited a band of increased tyrosine hydroxylase like immunoreactivity bordering the lesion cavity. Graft survival was limited in the non-lesioned animals but appeared enhanced in the animals whose striatum was previously lesioned. Lesion location within the striatum influenced the behavioral outcome. Large reductions in apomorphine-induced rotations could result from small lesions of the dorso-lateral striatum. These findings indicate that selective destruction of the caudate-putamen complex without tissue transplantation produces a dramatic reduction in the motor asymmetry of 6-OHDA treated rats. Suggested explanations for the decrease in induced rotational behavior with radiofrequency lesions include a decrease in the number of striatal dopamine receptors following cell destruction and lesion-induced recovery of host dopaminergic afferents. Striatal damage in critical areas can reverse some of the motor behavior associated with the 6-OHDA model and needs to be considered when evaluating the effects of neural grafting in this model.

Adrenal Medulla↗

Quantitative assessment of the effect of basal ganglia lesions on the stretch reflex in primates.

The effect of basal ganglia stereotactic lesions on motor tone in 3 primates was quantitated. The elastic and neurogenic forces generated with a controlled stretch of each animal's upper extremities were measured pre- and postlesion, and compared to previous studies. The techniques were sensitive to subtle changes in motor tone that were not clinically apparent. The results suggest that the basal ganglia, through the outflow path of the globus pallidus, is important in controlling the sensitivity of both flexors and extensors to stretch. These quantification techniques also have promise in evaluating treatment regimens for spasticity, rigidity, and other conditions with abnormal motor tone.

Animals↗

Imaging of cerebellar surface activation in vivo using voltage sensitive dyes.

The understanding of the information processing performed by complex neuronal networks in the central nervous system will require techniques permitting the simultaneous monitoring of the electrical activity of neuronal ensembles. Voltage sensitive dyes offer the potential for non-invasive optical monitoring of the activity in large populations of neurons. In this report we describe the use of voltage sensitive dyes and image processing techniques to monitor in vivo the activation of parallel fibers and associated neuronal events produced by stimulation of the cerebellar cortex in the rat. Despite the temporal limitations of video processing a relatively brief set of neuronal events was successfully imaged. Using this methodology we demonstrate that the detected fluorescent light changes were highly correlated with the evoked extracellular field potentials. Graded surface stimulation produced graded spatial patterns consistent with known parallel fiber anatomy and physiology. The optical signals were dependent on the presence of the voltage sensitive dyes and were abolished by topical application of a local anesthetic agent. In essence, activation of a parallel fiber beam and associated activity were imaged at relatively high resolution.

Animals↗

Conditional cross-interval correlation analyses with applications to simultaneously recorded cerebellar Purkinje neurons.

Two conditional cross-correlation techniques are described for the analysis of two simultaneously recorded neuronal spike trains. The conditional interspike interval histogram describes the distribution of interspike intervals of a neuron conditioned by a preceding spike in another neuron. The conditional cross-interval histogram describes the distribution of cross-intervals of two neurons conditioned by a preceding spike in one of the neurons. These techniques could be used to reveal the temporal coupling in the discharge of two neurons recorded simultaneously. The techniques augment the description of the correlation obtained with conventional cross-correlation measures. When applied to the simple spike discharge of simultaneously recorded cerebellar Purkinje neurons, the methods reveal temporal interactions between neurons that are not readily apparent from conventional cross-correlograms. The patterns observed suggest a tightly coupled, temporal surround-inhibition among nearby Purkinje neurons.

Animals↗

Alterations in simple spike activity and locomotor behavior associated with climbing fiber input to Purkinje cells in a decerebrate walking cat.

Recently we reported significant modulation of climbing fiber discharge in cerebellar Purkinje cells during normal and perturbed locomotion in the decerebrate cat walking on a treadmill. In this study covariation of simple spike activity and step cycle behavior with complex spike discharge were studied in decerebrate cats. Purkinje cell simple and complex spike discharge was recorded extracellularly in the intermediate region of lobules IV and V. Forelimb triceps and biceps electromyographic activity and displacement were monitored during the step cycle. A series of analyses were carried out to determine the temporal relationship between the complex spike discharge and forelimb step cycle, electromyographic activity and simple spike discharge. In this paper only the complex spike discharge associated with the onset of locomotion was evaluated. Using a sorting technique the amplitude of the forelimb step cycle and the associated triceps and biceps electromyographic activity covaried with complex spike discharge. For the majority of cells the alterations in the step cycle followed or occurred with the increase in complex spike discharge. However, in some cells the step cycle modifications preceded the increase in climbing fiber afferent activity. Another series of analyses employing an alignment technique demonstrated that a short term increase in simple spike discharge followed and was tightly coupled to the complex spike discharge. Additionally in most Purkinje cells an "oscillation" of simple spike activity which followed the complex spike discharge was uncovered. These observations support an important role for the climbing fiber afferent system in ongoing motor behavior. The results are consistent with the speculation that increased climbing fiber afferent input alters cerebellar cortical output which in turn can alter the ongoing motor behavior.

Animals↗

Relationships between simultaneously recorded Purkinje cells and nuclear neurons.

In decerebrate, unanesthetized cats, the activity of a Purkinje cell and a paired neuron in the interposed nuclei (subsequently referred to as a Purkinje cell-nuclear cell pair) were simultaneously recorded to compare their spontaneous discharge characteristics and responses to a peripheral input. Microstimulation techniques were used to determine if the two neurons were in related regions of the cerebellar cortex and interposed nuclei. First, the electrode used to record the interposed nuclear neuron was used to antidromically activate the Purkinje cell. Second, inhibitory responses with the appropriate time course were evoked in the interposed neurons with the Purkinje cell recording electrode. Both the spontaneous discharge of each pair as well as the cells' responses to a mechanically generated forepaw displacement were evaluated. A total of 35 Purkinje cell-nuclear cell pairs satisfying the microstimulation criteria were studied. During spontaneous activity there was no consistent relationship between the Purkinje cell simple spike activity and the nuclear neuron activity based on cross-correlation techniques. Auto-correlograms of both cells exhibited positive correlation for a brief time period. The variability of the interspike interval of the Purkinje cell discharge was greater than that for nuclear neurons, but there was no difference in the mean interspike interval for the pairs. The simple spike activity of Purkinje cells in response to sinusoidal displacements of the forepaw was weakly modulated. The modulation was limited to a small frequency range (2-7 Hz). In contrast the nuclear neurons exhibited a greater depth of modulation than Purkinje cells and responded to a wider range of frequencies (2-15 Hz). For many pairs of cells the relationship between the Purkinje cell and nuclear neuron discharge was not reciprocal. The responses of Purkinje cell-nuclear cell pairs to forepaw displacement were more often reciprocal to square wave than to sinusoidal stimuli. Using a technique which estimated the reciprocity of Purkinje cell and nuclear cell responses, 49% of the responses were reciprocal while 51% were not. These findings suggest that a nuclear neuron's discharge characteristics are not dominated by inputs from a single Purkinje cell and the firing relationship between a Purkinje cell and a related nuclear cell need not be reciprocal.

Animals↗