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M R DeLong

Publications and source records attributed to M R DeLong.

At least 55 records · Page 3Linked to original sources
PubMed1996

Functional and pathophysiological models of the basal ganglia.

Because of new data, anatomical and functional models of the basal ganglia in normal and pathological conditions (e.g. Parkinson's and Huntington's diseases) have recently come under greater scrutiny. An update of these models is clearly timely, taking into consideration not only changes in neuronal discharge rates, but also changes in the patterning and synchronization of neuronal discharge, the role of extrastriatal dopamine, and expanded intrinsic and input/output connections of these nuclei.

Animals↗
PubMed1996

Microstimulation of primate motor thalamus: somatotopic organization and differential distribution of evoked motor responses among subnuclei.

1. The functional organization of motor responses to microstimulation throughout the primate "motor" thalamus including nucleus ventralis lateralis, pars oralis (VLo); nucleus ventralis posterior lateralis, pars oralis (VPLo); nucleus ventralis lateralis, pars caudalis (VLc); and portions of ventralis anterior (VA) and area X, was systematically studied in awake monkeys. A total of 2,021 sites were examined for their response to microstimulation. Of these, 1,123 were histologically verified as to their location within the motor thalamus. At or near each site, isolated neurons were examined for their responses to somatosensory examination and active movement (n = 1,272). This study was carried out as part of a larger study examining the responses of neurons in the motor thalamus to somatosensory examination, torque-induced limb perturbations, and active movement in a visuomotor step-tracking task. 2. Microstimulation at < or = 40 microA evoked movements in the contralateral limbs, trunk, or face. Evoked movements of the limb were generally maximal about a single joint. 3. There was a differential response to microstimulation between subnuclei of the motor thalamus. In order of decreasing frequency, the percentages of sites within each subnucleus from which movements were evoked were as follows: VPLo, 93% (449 of 483); VLo, 21% (57 of 272); VLc, 11% (15 of 140); VA, 1% (1 of 85); and reticular nucleus, 0% (0 of 65). In VPLc, 44% (34 of 78) of sites examined were microexcitable. However, these were almost all within 500 microns of the border of VPLo, suggesting they may have occurred as a result of current spread to adjacent VPLo. Although area X was not sampled in its entirety, it did not appear to be microexcitable. 4. Microexcitable responses had a somatotopic organization, similar to that for neuronal responses to sensorimotor examination, with leg responses found most laterally and arm and face responses found progressively more medially. 5. Zones in VPLo generally ranging from 500 to 1,500 microns were found in which microstimulation resulted in the same motor response. These microexcitable zones resemble those described for the striatum and were termed thalamic microexcitable zones (TMZ). TMZs also resemble cortical efferent zones in that both are somatotopically organized, may affect a single muscle or group of muscles, have low thresholds for microstimulation with sharp boundaries that lie adjacent to other microexcitable zones with the opposite effects, and are of approximately the same dimension. 6. This study suggest that a fundamental unit of motor organization, i.e., single muscle or joint, is preserved at the thalamic level in the form of TMZs, and that these fundamental units of organization may contribute to the modular organization of the cortex.

Animals↗
PubMed1994

Synaptic innervation of neurones in the internal pallidal segment by the subthalamic nucleus and the external pallidum in monkeys.

In order to better understand the way by which the subthalamic nucleus interacts with the globus pallidus to control the output of the basal ganglia, we carried out a series of experiments to investigate the pattern of synaptic innervation of the pallidal neurones by the subthalamic terminals in the squirrel monkey. To address this problem we used the anterograde transport of biocytin. Following injections of biocytin in the subthalamic nucleus, rich plexuses of labelled fibres and varicosities formed bands that lay along the medullary lamina in both segments of the ipsilateral pallidum. At the electron microscopic level, two populations of biocytin-containing terminals were identified in the internal pallidum (GPi). A first group of small to medium-sized terminals (type 1; mean cross-sectional area +/- S.D. = 0.41 +/- 0.04 microns 2) contained round vesicles and formed asymmetric synapses with dendritic shafts (95%) of mixed sizes (maximum diameter ranging from 0.3 to 4.0 microns) and spine-like structures (5%). The second group of terminals (type 2) contained pleiomorphic vesicles, had a larger cross-sectional area (mean +/- S.D. = 0.9 +/- 0.4 micron 2) and formed symmetric synapses predominantly with perikarya (41%) and large dendrites (57%). In some cases, the two types of terminals converged at the level of single GPi neurones. Postembedding immunogold method revealed that the type 2 terminals displayed gamma-aminobutyric acid (GABA) immunoreactivity, whereas the type 1 terminals did not. In the external pallidum (GPe), injections in the subthalamic nucleus labelled both type 1 or type 2 terminals. However, the labelled type 2 boutons were much less abundant in GPe than in GPi. The presence of biocytin-labelled perikarya in GPe and the fact that the type 2 terminals displayed GABA immunoreactivity led us to suspect that these terminals were derived from axons of GPe neurones. In agreement with this hypothesis, injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) in GPe labelled terminals in GPi that displayed the morphological features and a pattern of synaptic organization similar to the type 2 terminals. In conclusion, the results of our study demonstrate that the subthalamopallidal terminals form asymmetric synapses that are distributed along the dendritic tree of GPe and GPi neurones. In contrast, the GPe projection to GPi gives rise to large GABA-containing terminals that form symmetric synapses predominantly with the proximal region of pallidal neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Physiologic properties and somatotopic organization of the primate motor thalamus.

1. To examine the functional organization of the primate "motor" thalamus, neuronal activity was studied systematically in awake behaving monkeys throughout the nucleus ventralis lateralis, pars oralis (VLo), nucleus ventralis posterior lateralis, pars oralis (VPLo), ventralis lateralis, pars caudalis (VLc), and portions of ventralis anterior (VA) and Area X. In addition, portions of the sensory nucleus ventralis posterior lateralis, pars caudalis (VPLc) were explored. Isolated neurons were examined for their responses to somatosensory examination and active movement (n = 919) and for their response to torque-induced joint displacements (n = 375). A total of 684 neurons was determined histologically to lie within specific subnuclei of the motor (n = 574) or sensory (n = 110) thalamus. 2. The sensorimotor response properties of neurons in the thalamic subnuclei showed clear differences in their response to somatosensory examination. In order of decreasing frequency, the percent of neurons responding to passive somatosensory examination in each subnucleus were as follows: VPLc, 96% (106/110), VPLo, 93% (252/270), VLc, 77% (43/56), VLo, 37% (59/155), Area X, 22% (12/53), and VA, 12% (5/40). Conversely, neurons that responded only to active movement were most frequent in VLo, 44% (68/155), VA, 45% (18/40), and Area X, 40% (21/53) and relatively infrequent in VLc 11% (6/56) and VPLo, 3% (7/270). In VPLc, no neurons were found that responded only to active movement (0/110). 3. A well-defined somatotopic organization was found in VLo, VPLo, and VPLc and was suggested strongly for VLc. Individual body regions were represented in a series of lamellae, organized in a partial onion skin-like arrangement with the leg represented in the outermost lamella, and the trunk, arm, and orofacial regions represented in successively deeper lamellae. In general the body representations, although present for each subnucleus thoroughly examined, i.e., VLo, VPLo, and VPLc, also were contiguous across subnuclei. Based on the available data, a clear somatotopic picture could not be discerned for Area X or VA. 4. Responses to torque application were more common in neurons in VPLo (77%; 60/78) and VLc (73%; 16/22) than in VLo (44%; 12/27). Mean latencies were shortest for neurons in VPLo (25 +/- 14 ms; mean +/- SD) and the bordering (shell) region of VPLc (22 +/- 15 ms) and were approximately twice as long in VLc (51 +/- 23 ms) and VLo (47 +/- 21 ms).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

The primate subthalamic nucleus. I. Functional properties in intact animals.

1. The present study tests several key aspects of the current model of the intrinsic circuitry of the basal ganglia, in particular the degree to which basal ganglia-thalamocortical circuits are functionally segregated at the level of the subthalamic nucleus (STN). To this end the responses of STN cells to somatosensory examination (n = 301 cells), the polarity and latencies of neuronal responses to passive and active movements (n = 223 cells), responses to microstimulation (n = 1589 sites), and cross-correlation functions of pairs of neighboring neurons (n = 72 pairs) were studied in STNs of three African green monkeys. 2. The activity of 55% of cells examined in STN was briskly modulated in response to passive movements of individual contralateral body parts. Of these, 86% responded to passive joint rotation of muscle palpation, but in some cases (25% of responding cells) responses were also elicited by light touch. In 91% of the responding cells responses were elicited by manipulations around a single joint only. 3. The caudoventral sector in STN was largely devoid of cells with responses to somatosensory stimulation. Within the rostrodorsal zone a lateral region containing neurons that responded to arm movements and a more medial region with neurons responding to leg movement were found. Cells responding to orofacial movements were located more dorsally and rostrally. Neurons with similar responses to active and passive movements of the limbs tended to be clustered within "arm" and "leg" zones. 4. Of identified arm cells in STN (n = 80), 36% responded to the application of torque pulses to the elbow (43 responses overall). Forty-eight percent of these cells responded to both extension and flexion torques. Ninety-three percent of the responses were initial increases in discharge, which characteristically occurred earlier and were shorter than initial decreases. Fifty-three percent of the responses were biphasic or multiphasic. 5. During active step tracking movements 40% of STN arm cells (n = 53 cells) responded with significant changes in activity. Thirty-six percent of these cells showed responses with both extension and flexion movements. Of the responses, 90% were increases in discharge. Only 14% of all responses were biphasic or multiphasic. Responses tended to occur around the time of movement onset (average latency 2 ms after movement onset). 6. Microstimulation (bipolar pulses, 40 microA, 200-500 ms train duration, 400 Hz) of the core of STN itself did not appear to produce movement.4+ synchronized activity in only 11% of pairs.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism.

1. The neuronal mechanisms underlying the major motor signs of Parkinson's disease were studied in the basal ganglia of parkinsonian monkeys. Three African green monkeys were systemically treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) until parkinsonian signs, including akinesia, rigidity, and a prominent 4- to 8-Hz tremor, appeared. The activity of neurons in the subthalamic nucleus (STN) and in the internal segment of the globus pallidus (GPi) was recorded before (STN, n = 220 cells; GPi, n = 175 cells) and after MPTP treatment (STN, n = 326 cells; GPi, n = 154 cells). 2. In STN the spontaneous firing rate was significantly increased from 19 +/- 10 (SD) spikes/s before to 26 +/- 15 spikes/s after MPTP treatment. Division of STN neurons recorded after MPTP treatment into cells with rhythmic bursts of discharge occurring at 4-8 Hz (as defined by autocorrelation analysis) and neurons without 4- to 8-Hz periodic activity revealed an even more prominent increase in the firing rate of the 4- to 8-Hz oscillatory neurons. 3. In GPi overall changes in the average firing rate of cells were inconsistent between different animals and behavioral states. However, the average firing rate of the subpopulation of neurons with 4- to 8-Hz periodic oscillatory activity after treatment with MPTP was significantly increased over that of all neurons before MPTP treatment (from 53 to 76 spikes/s, averaged across monkeys). 4. In the normal state the percentage of neurons with burst discharges (as defined by autocorrelation analysis) was 69% and 78% in STN and GPi, respectively. After MPTP treatment the percentage of cells that discharged in bursts was increased to 79% and 89%, respectively. At the same time the average burst duration decreased (from 121 +/- 98 to 81 +/- 99 ms in STN and from 213 +/- 120 to 146 +/- 134 ms in GPi) with no significant change in the average number of spikes per burst. 5. Periodic oscillatory neuronal activity at low frequency, highly correlated with tremor, was detected in a large number of cells in STN and GPi after MPTP treatment (average oscillation frequency 6.0 and 5.1 Hz, respectively). The autocorrelograms of spike trains of these neurons confirm that the periodic oscillatory activity was very stable. The percentage of cells with 4- to 8-Hz periodic activity significantly increased from 2% to 16% in STN and from 0.6% to 25% in GPi with the MPTP treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism.

1. The effects of reversible and irreversible pharmacological manipulations of the neuronal activity in the subthalamic nucleus (STN) on parkinsonian motor signs and neuronal activity in the internal segment of the globus pallidus (GPi) were studied in African green monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2. Muscimol injections (< or = 1 microliter, 1 microgram/microliter) into STN reduced neuronal activity recorded at the injection site within minutes. This was immediately followed by reduced akinesia, tremor, and rigidity, as well as the emergence of dyskinesias in contralateral limbs. The motor effects were accompanied by generalized behavioral activation, lasted between 10 and 60 min, and were strongly dependent on the site of injection, with injections into the lateral "arm area" of STN first affecting contralateral arm movements and injections into the "leg" area affecting leg movements first. 3. Bicuculline injections (< or = 1 microliter, 1 microgram/microliter) into STN marginally increased the neuronal activity and induced neuronal discharge in bursts. Rigidity, akinesia, and tremor in the contralateral limbs were not changed. 4. Injections of ibotenic acid in two animals (2 and 7 microliters, 10 micrograms/microliters) resulted in 70 and 51% destruction of STN, respectively. Similarly to the muscimol injections, this resulted in a reduction of the neuronal activity, a reversal of parkinsonian motor signs, and the development of dyskinesias in the contralateral limbs. 5. Although tremor was significantly reduced after STN lesions, periodic oscillatory neuronal activity in GPi persisted. The strength of modulation of the neuronal oscillation was not significantly changed after STN lesion. 6. The percentage of cells in GPi exhibiting increases in discharge in response to torque application was significantly reduced after STN lesion. The magnitude and duration of the responses with increase in firing rate were reduced after STN lesioning. 7. These results support the hypothesis that abnormally increased tonic and phasic activity in STN leads to abnormal GPi activity and is a major factor in the development of parkinsonian motor signs. Furthermore they imply that cells in the basal ganglia have the intrinsic property of discharging in periodic bursts, which is unmasked under parkinsonian conditions.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Role of the thalamus in parkinsonian tremor: evidence from studies in patients and primate models.

The electrophysiologic basis of parkinsonian tremor is discussed in terms of the central oscillator and peripheral feedback hypotheses of tremor. Recent studies in monkeys and humans suggest that parkinsonian tremor may result from the activity of a central oscillator, possibly located in the basal ganglia. Peripheral somatosensory input seems to modulate tremor and central nervous system activity related to tremor.

Animals↗
PubMed1992

A personal computer-based spike detector and sorter: implementation and evaluation.

Many studies of neuronal activity require isolation of the extracellular wave form (spike) of a single neuron from the potentials generated by nearby cells. A variety of methods for spike sorting exists, but most are expensive and require specialized hardware and software. Moreover, there is no easy and objective way for evaluating and comparing the performance of spike sorting devices. We describe here a system for on-line spike sorting that is implemented on an IBM PC/AT computer using commercially available hardware and C-language software. Spikes are detected after crossing an amplitude threshold and are sorted or rejected by template matching. The templates are constructed in a learning phase, using a fast manual sorting of all detected spikes. Later, each detected spike is matched against all defined templates. A detected spike which does not match any template, or matches more than one, is rejected. A continuous display of the wave forms of the last 256 sorted, double-matched, and rejected spikes is used as the main tool for parameter adjustment and error detection. Also described is a new and highly versatile tool for generating appropriate wave forms for critical evaluation of sorter performance. Using the same hardware and software tools, a simulation program mimics the extra-cellular activity of several neurons by linear combination of two vectors and added random noise. The size, shape and the variability of the action potential, as well as its firing pattern, can be adjusted. Comparison of the sorter output with the known simulated activity is used to examine the sorter performance and limitations.

Action Potentials↗
PubMed1992

Excitotoxic acid lesions of the primate subthalamic nucleus result in transient dyskinesias of the contralateral limbs.

1. To examine the role of the subthalamic nucleus (STN) in the pathogenesis of dyskinesias, the STN was experimentally lesioned with fiber-sparing excitotoxins in two awake monkeys. 2. A combined recording-injection device was used to locate and lesion the STN accurately under physiological guidance. A small amount (1 microliters) of ibotenic acid (10 micrograms/microliters) or kainic acid (1 micrograms/microliters) was injected into each of four to seven target sites in the STN. Postmortem histology confirmed that lesions were confined to the STN, and the volume of each lesion at each site was 4-11% of the total volume of the nucleus. 3. Approximately 20 min after the end of each injection, the frequency of movements increased in the distal portions of the upper and lower limbs contralateral to the injection site. Severe dyskinesias, involving the proximal joints to a greater degree than the distal, developed in the contralateral limbs after 60-80 min and lasted < or = 4 h. The pattern of involvement and time course were similar after each lesion. In the days after the lesioning, only rare dyskinesias were observed in the contralateral hands and feet, typically occurring when the animals were stimulated. 4. Despite the severe dyskinesias, there was no obvious effect on voluntary movements such as grooming or reaching. 5. These results suggest that reduction of STN activity plays a role in the production of dyskinesias.

Animals↗
PubMed1992

Excitotoxic acid lesions of the primate subthalamic nucleus result in reduced pallidal neuronal activity during active holding.

1. To gain a better understanding of the pathophysiology of hemiballismus in primates, and to test directly the hypothesis that the subthalamopallidal projection is excitatory, we studied the effects of lesions of the subthalamic nucleus (STN) on neuronal activity in the globus pallidus (GP) of monkeys during performance of a motor behavioral task. 2. Animals were trained to position and hold a manipulandum to which torque pulses were applied, producing elbow flexion and extension. The activity of neurons in the external (GPe) and internal (GPi) segments of GP was recorded in two monkeys during task performance before and after STN lesions. The STN was lesioned by the fiber-sparing neurotoxins ibotenic acid and/or kainic acid. 3. After lesioning, the firing rate of neurons in both segments of GP, which was measured during the period of holding before torque application, was significantly decreased in both animals. The mean of discharge rates of GPi neurons decreased (P < 0.001) from 69.8 (n = 169, SD = 21.6) to 47.4 spikes/s (n = 180, SD = 22.6) after lesioning. The mean of discharge rates of GPe neurons decreased from 63.6 spikes/s (n = 218, SD = 25.1) before lesions to 41.0 spikes/s (n = 208, SD = 18.1) after lesioning. 4. These results provide further evidence that STN gives rise to a major excitatory input to both segments of the GP and support the hypothesis that dyskinesias result from decreased GPi output.

Animals↗
PubMed1991

Organization of striatopallidal, striatonigral, and nigrostriatal projections in the macaque.

The topographic organization of neostriatal connections was investigated by axonal transport of horseradish peroxidase, tritiated amino acids, or mixtures of both injected into the neostriatum of macaque monkeys. Striatal projections to pallidum and substantia nigra and the origin of projections to striatum from cerebral cortex and substantia nigra were examined. All striatal injections gave rise to projections to external and internal pallidum and to substantia nigra. Injections in caudate nucleus and in putamen both gave rise to substantial projections to pallidum and to substantia nigra, and the ratio of pallidal and nigral projections was generally similar. The striatopallidal projection showed prominent arborizations at right angles to the striatofugal pathway traversing the pallidum, forming in this manner terminal fields consisting of multiple bands or discs within a broad segment of the pallidum. Thus separate but neighboring regions of striatum appeared to have overlapping pallidal projection territories. In broad terms, rostral striatum projects to rostral pallidum, caudal striatum to caudal pallidum, and dorsal and ventral striatum, respectively, to dorsal and ventral pallidum. Inner (medial) and outer (lateral) putamen showed only subtle differences in pallidal projection patterns. The striatonigral projection from each injected area of striatum formed a longitudinal band extending over the entire length of the substantia nigra, with scattered, dense terminal fields occupying portions of pars compacta as well as pars reticularis. Rostral striatum projected to medial nigra and caudal striatum to lateral nigra. Terminal fields from ventral striatum were located somewhat more dorsally in the substantia nigra than those from dorsal striatum. Neighboring but separate regions of striatum appeared to have overlapping nigral projection territories, especially in caudal nigra. The nigrostriatal neurons projecting to an injected area of striatum generally were located in the same longitudinal band of the substantia nigra as the corresponding striatonigral projection. Labeled pars compacta neurons were often surrounded by a dense, labeled striatonigral terminal field, suggesting the existence of a striato-nigrostriatal loop. The rostromedial pars compacta contained labeled neuronal cell bodies in most cases, suggesting a widely divergent projection to striatum from this cell group. A slight tendency for preferential cell labeling rostrally in nigra with rostral striatal injection and caudally in nigra with caudal injections was noted. The preferred relationship of lateral nigra with caudal striatum and medial nigra with rostral striatum has implications for clinical expression of Parkinson's disease, which may vary with differential involvement of different nigral cell groups along the medial to lateral axis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Electrophysiological studies of the functions of the nucleus basalis in primates.

In summary, the studies reviewed here have indicated which neural functions might be directly influenced by the nucleus basalis. Basalis neurons do not appear to be directly involved in trial-specific memory because, in memory tasks, they have non-differential responses that do not correspond to the information being remembered by the monkey. Similarly, basalis neurons do not appear to be related to movements because, in a go/no-go task, similar neuronal responses occur whether the animal moves or does not move, and, in a delayed response task, different neuronal responses occur during the same arm movement made under different conditions. Basalis neurons also respond differently to the same sensory stimuli presented under different conditions, which indicates that the nucleus basalis is not involved in basic sensory perception. The responses of basalis neurons therefore appear to be strongly influenced by the context or behavioral significance of stimuli. Many basalis neurons respond to appetitive stimuli. In trained animals, the most frequently observed responses have been to a water reward or to stimuli that consistently precede the reward. In naive, thirsty animals, a large proportion of basalis neurons respond to the delivery of water. However, a large number of neurons also respond to an aversive air puff, which indicates that the nucleus basalis cannot be exclusively related to appetitive stimuli. Although some basalis neurons apparently respond only to the appetitive stimulus and others respond only to the aversive stimulus, the majority appear to respond similarly to both stimuli. In particular, almost all of the neurons whose response magnitudes covary with the volume of the water respond similarly to the air puff. Hence, the neurons that appear most likely to be related to the appetitive component of the water are also responsive to an aversive stimulus. Basalis neurons may therefore be related to some common characteristic of aversive and appetitive stimuli, such as the arousing quality of these stimuli. The hypothesis that most basalis neurons are particularly responsive to arousing stimuli could account for the abundance of responses to rewards and stimuli associated with rewards. These phasic responses of basalis neurons are hypothesized to be related to a transient increase in the cortical activation component of arousal, just as the tonic activity of basalis neurons appears to be related to sustained cortical activation.

Animals↗
PubMed1991

Transient impairment of recognition memory following ibotenic-acid lesions of the basal forebrain in macaques.

To assess the contributions of the basal forebrain cholinergic nuclei to visual recognition memory in macaques, we compared the effects of lesions of (a) the nucleus basalis of Meynert, (b) the medial septal and diagonal band nuclei, and (c) all nuclei combined on performance of delayed nonmatching-to-sample with trial-unique stimuli. Whereas monkeys with the separate lesions did not differ from each other or from normal control animals, those with combined lesions showed a significant impairment. With time and extended practice, however, the performance of the animals with combined lesions recovered to normal levels. During the recovery period, these monkeys showed an initially increased sensitivity to scopolamine that later dissipated, at which time they also failed to show the improvement that follows physostigmine administration in normal animals. Postmortem assessment of cortical choline acetyltransferase activity revealed that only the group with combined lesions had significant depletion of this enzyme. The results suggest that (1) the basal forebrain cholinergic system participates in mnemonic processes in primates and that (2) extensive damage to this system is necessary before impairments in recognition memory, even transient ones, can be observed.

Acetylcholinesterase↗
PubMed1990

Reversal of experimental parkinsonism by lesions of the subthalamic nucleus.

Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Wilson's disease. Development of neurological disease after beginning penicillamine therapy.

Patients with neurological symptoms and signs of Wilson's disease have been frequently noted to have a worsening of their condition after beginning chelation therapy with D-penicillamine. Presymptomatic patients, however, are not expected to develop neurological manifestations once appropriate therapy is begun. We describe a patient who was seen with hepatic disease and no neurological symptoms who became neurologically incapacitated soon after beginning penicillamine therapy. This case identifies an unexpected complication of penicillamine therapy that should be watched for in the presymptomatic patient who is beginning therapy.

Adult↗