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Biomedical subjects

W Schultz

Publications and source records attributed to W Schultz.

At least 109 records · Page 6Linked to original sources
PubMed1986

The catecholamine uptake blocker nomifensine protects against MPTP-induced parkinsonism in monkeys.

Administration of MPTP (1-methyl-1,2,3,6-tetrahydropyridine) to Macaca fascicularis monkeys produced severe parkinsonism (hypokinesia, tremor, rigidity, aphagia, adipsia) and more than 90% loss of nigral dopamine neurons, striatal dopamine content and striatal 3H-mazindol binding. Treatment with the catecholamine uptake blocker nomifensine counteracted the behavioral, histological and neurochemical effects induced by MPTP. For obtaining best protection, nomifensine had to be administered for weeks after MPTP. The results suggest that the selective target-directed neurotoxic action of MPTP on dopamine neurons in monkeys is mediated via the dopamine uptake mechanism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

The distribution of metastases of different primary tumors in the liver.

The distribution of the number and volume of liver metastases in both lobes of the liver was investigated. The density of the metastases and their volume were analyzed. The study of 71 human metastatic livers revealed an almost homogeneous pattern of metastatic distribution. There was no difference whether the spread of the tumor cells had occurred via the portal vein or the hepatic artery. Both sides of the liver were affected similarly.

Hepatic Artery↗
PubMed1986

Activity of pars reticulata neurons of monkey substantia nigra in relation to motor, sensory, and complex events.

The behavioral involvement of neurons in the pars reticulata of the substantia nigra (SNpr) in sensory and motor processes was investigated in order to contribute to the understanding of behavior-related neuronal mechanisms in the basal ganglia, of which the SNpr is a major output station. Electrophysiological properties of SNpr neurons were studied with extracellular recordings from single neurons in monkeys performing in a behavioral GO/NO-GO paradigm, employing significant auditory and visual stimuli, forelimb reaching movements, and mouth movements. Neurons in the SNpr discharged impulses of 0.6 to 1.0 ms in duration, at rates of 23 to 145/s (median 68/s). They contrasted with dopaminergic pars compacta neurons of substantia nigra, which discharged longer impulses at rates below 8/s. Two-thirds of more than 100 quantitatively and statistically evaluated SNpr neurons showed changes with temporal relationships to at least one of the events of the behavioral task. One-fifth of all neurons covaried with more than one event. The largest group of task-related neurons increased or decreased activity with contralateral forelimb movements (46% of all neurons). Most of them covaried with large forward reaching of the arm, and only the minority covaried with distal forearm manipulation. None of the SNpr neurons resembled in their changes the timing of activity of single muscles. Many neurons also showed changes with ipsilateral movements, in a similar fashion as on the contralateral side. Changes began rarely before and mostly with or after onset of muscle activity in prime movers. Changes were quantitatively moderate, rarely exceeding a doubling of discharge rate with increases and reductions by 50% with decreases. Movement relations did not appear to be due to somatosensory input. Some neurons increased or decreased their activity in relation to mouth movements (16% of all neurons). Changes were quantitatively moderate as in the case of movement relationships. Nine percent of all neurons decreased their activity after an acoustic preparatory signal and 9% after a light stimulus indicating the GO or NO-GO situation. Latencies were 50-150 ms (median 90 ms) for the auditory and 80-200 ms (median 120 ms) for the visual responses. Twelve percent of all neurons increased or decreased their activity during the waiting and preparation period, which lay between an initial sensory signal and the permission to move for reward.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Responses of midbrain dopamine neurons to behavioral trigger stimuli in the monkey.

Destruction of the midbrain dopamine (DA) system in Parkinsonian man and experimental animals leads to deficits in initiation of behavior, motor performance, and cognitive mechanisms. We have investigated the extracellular impulse activity of single midbrain DA neurons in unlesioned monkeys performing in a controlled behavioral task that was designed to paradigmatically test behavioral reactivity. Animals were trained to execute natural forelimb reaching movements for food reward in response to a trigger stimulus. Presumptive DA neurons were histologically located in the pars compacta of substantia nigra and in neighboring areas A8 and A10. They spontaneously discharged polyphasic impulses of relatively long duration (1.4-3.6 ms) and at low frequencies (0.5-8.5/s). Systemic injections of low doses of the DA autoreceptor agonist apomorphine (0.05-0.2 mg/kg) depressed the activity of virtually all thus tested DA neurons. In following established criteria, these characteristics strongly suggest the DAergic nature of the recorded neurons. The majority of midbrain DA neurons (70 of 128) responded to the behavioral trigger stimulus of the task with a short burst of impulses. Latencies ranged from 39 to 105 ms (median 65 ms) for onset and from 65 to 165 ms (median 95 ms) for peak of responses. Responses occurred before arm movement and at the time of or before onset of electromyographic (EMG) activity in prime mover muscles. Responses were time-locked to the stimulus and not to the onset of movement or EMG. Responses remained present in most neurons but were reduced when vision of the behavioral trigger stimulus was prevented while maintaining the associated acoustic signals. In another variation of the task, most neurons also responded to a stimulus that was physically identical to the behavioral trigger but to which the animal made no movement. The activity of a few DA neurons (11 of 128) was reduced following presentation of the behavioral trigger stimulus, with latencies comparable to those of activations. The activity of many DA neurons was increased (40 of 128) or reduced (22 of 128) during execution of the forelimb reaching movement. These changes were of a slow and moderate nature, and were minor compared with responses to the behavioral trigger stimulus. About half of movement-related neurons also responded to the behavioral trigger. The activity of a few DA neurons was increased (11 to 128) or reduced (1 to 128) when the food reward reached the mouth. These changes did not occur with spontaneous mouth movements. About half of these neurons also responded to the behavioral trigger.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Prolonged changes in dopaminergic terminal excitability and short changes in dopaminergic neuron discharge rate after short peripheral stimulation in monkey.

Time-courses of responses to peripheral somatosensory stimulation were studied in the nigrostriatal dopamine (DA) system by comparing rates of neuronal discharges with changes in nerve terminal excitability, an indicator of DA release. The excitability of DA nerve terminals in the putamen was assessed as probability for evoking an antidromic response in substantia nigra DA cells with electrical stimulation in an anesthetized monkey. At about 30-60% decrease of excitability was seen during and about 15 min beyond pain pinch stimulation (PPS) in 12 of 17 tested DA neurons, while 4 neurons showed a 40% increase. Discharge rates were decreased in 7 and increased in 5 of the 17 DA neurons during, but not after PPS. It is concluded that the release of DA in the striatum may be controlled in two ways: rapid reactions would be mediated by changes in discharge rate, while slower, prolonged responses could be due to presynaptic interactions with other striatal afferents.

Action Potentials↗
PubMed1985

Deficits in behavioral initiation and execution processes in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to two monkeys led to hypokinesia, tremor, rigidity, adipsia and aphagia. Quantitative assessment of hypokinesia revealed increased reaction time, delayed onset of muscle activity and prolonged movement time in a forelimb reaching task after selective degeneration of the nigrostriatal dopamine (DA) system sparing mesocortical dopamine neurons. The losses of pars compacta cells of substantia nigra, of striatal [3H]mazindol binding and of striatal DA content (more than 90%) quantitatively paralleled the severity of behavioral deficits. Additional monoamine systems were affected with stronger MPTP effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Responses of rat pallidum cells to cortex stimulation and effects of altered dopaminergic activity.

The aim of the study was to investigate the influences of dopamine on oligosynaptic corticopallidal neurotransmission. Different cortical areas were electrically stimulated and the responses in the pallidum were recorded by single-cell electrophysiology. Out of 377 pallidal neurons, 192 (51%) responded to stimulation of at least one of the cortical areas investigated. Convergence between frontal cortex and at least one of the other cortical areas was seen in 59 of 110 (54%) pallidal neurons responding to frontal cortex stimulation. Nearly three-quarters (73%) of all responsive pallidal neurons showed a short latency reduction of activity following the stimulus, the rest responded with pure activation or an activation-depression sequence. The dopaminergic influences on this corticopallidal impulse transmission were assessed by the systemic administration of the dopamine receptor-blocking neuroleptics, haloperidol and fluphenazine, as well as by conditioning electrical stimulation of the substantia nigra. Neuroleptic administration augmented the responses to cortical stimulation in 12 of 34 pallidal neurons. Stimulation of the substantia nigra diminished the responses in 24 and augmented them in 6 of 63 of the tested neurons. We propose from the present results, and in agreement with data from conceptually different studies done by others, that dopaminergic influences reduce the flow of information from the cortex to the pallidum. This may constitute a focussing mechanism by which only information form the strongest cortical inputs would pass to the pallidum while less prominent activity would be lost.

Animals↗
PubMed1984

The activity of pars compacta neurons of the monkey substantia nigra is depressed by apomorphine.

In the substantia nigra of anesthetized and awake monkeys, presumptive dopamine cells of the pars compacta were electrophysiologically discriminated against non-dopaminergic cells of the pars reticulata by their lower discharge rate (0.5-8 vs 20-130 imp./s), their longer impulse duration (means 2.05 vs 0.92 ms), and their exclusive depression following systemic injection of the dopamine agonist apomorphine (24 out of 30 compacta neurons at 0.05-0.1 mg/kg s.c.).

Action Potentials↗
PubMed1984

Recent physiological and pathophysiological aspects of Parkinsonian movement disorders.

Deficits in the neural control of limb movements constitute a major part of Parkinsonian symptoms and are linked to a decay of dopaminergic neurotransmission. In animal models, Parkinsonian-like hypokinesia is consistently reproduced with large nigrostriatal dopamine depletions, while tremor and rigidity are less readily obtained. Lesions leading to a less than 70% striatal dopamine depletion are largely compensated by an increased activity of dopamine terminals. With more important lesions, supersensitivity of striatal non-adenylate cyclase-linked dopamine receptors occurs. Electrophysiological studies in Parkinsonian patients demonstrate increased reaction times and a reduced build-up of movement-related muscular activity underlying hypokinesia and provide circumstantial evidence for a central origin of tremor and rigidity. Single cell activity in unlesioned, behaving monkeys shows an increasingly direct relationship to movements when following the neural connections from mid-brain dopamine cells via striatum, globus pallidus, thalamus to pyramidal tract neurons of motor cortex. These data corroborate experimentally the concept that Parkinsonian hypokinesia is due to a failure of basic behavioral activating mechanisms.

Animals↗
PubMed1981

The somatotopy of the gracile nucleus in cats with agenesis of a hindfoot.

The somatotropic representation of the hindlimb in the gracile nucleus was studied in two cats who had a congenital defect of one hindfoot. The defect comprised all of the foot downward from and including the heel, and the distal third of tibia and fibula. The part of the sciatic nerve normally supplying the lower hindlimb and the hindfoot was reduced in diameter by one third. The motoneurones corresponding to the absent muscles were lacking and replaced by glial elements. The cross-sectional area of the dorsal columns at segment S2 was reduced by more than 20%. The gracile nuclei, in contrast, were not reduced in size. Only the diameter of its neurones was significantly smaller. Electrophysiological single and multi-neurone recordings revealed an altered somatotopic representation in the gracile nucleus on the defective side. The nuclear area normally representing the missing parts of the body surface now received input from the stump. There was no nuclear area devoid of afferent input, and there was no input in the gracile from the forelimb or from the contralateral side. It is concluded that the remaining parts of the leg project onto the gracile nucleus in an ordered fashion, sharing the entire nucleus according to their present afferent fibres.

Afferent Pathways↗
PubMed1981

[Influence of dopamine on pars reticulata neurones of substantia nigra (author's transl)].

1 Dendrites of the dopamine neurones of pars compacta extend into pars reticulata of substantia nigra. The aim of the present study was to investigate whether dendritically released dopamine would be able to influence pars reticulata neurones. 2 In order to test this hypothesis, we have studied the effects of iontophoretically applied dopamine on pars reticulata neurones of substantia nigra in rats under chloralhydrate and under urethane anaesthesia. 3 The dopamine neurones of pars compacta and the neurones of pars reticulata were distinguished by their histological localization (Fig. 1 A) and their electrophysiological characteristics (Fig. 2). Sixty percent of reticulata neurones were antidromically excited from ipsilateral ventromedial thalamus (Fig. 4). 4 Both nigrothalamic and non-nigrothalamic neurones of pars reticulata were activated by iontophoretically applied dopamine, but never depressed (Fig. 5). This effect was blocked by iontophoretically applied fluphenazine. 5 The percentage of reticulata neurones excited by dopamine depended upon the anaesthetic agent: 39% when chloralhydrate, 8% when urethane was used (Table I). 6 As described before by others, dopamine neurones were depressed by dopamine (82%), but never excited (Fig. 6). This effect was also sensitive to fluphenazine. 7 The present results would support the concept that dendritically released dopamine not only affects other nigral dopamine neurones, but also influences non-dopaminergic nigral neurones, some of which project outside the basal ganglia.

Action Potentials↗
PubMed1980

Dopaminergic activation of reticulata neurones in the substantia nigra.

Dendritic release of dopamine (DA) in substantia nigra (SN) is well established in various experimental situations. Morphological substrates for DA storage exist in dendrites, as do dendro-dendritic and dendro-axonic contacts. DA receptors in SN are located on both cells and striato-nigral terminals. DA is thought to regulate the activity of neighbouring dopaminergic neurones through its dendritic release by a local feedback mechanism. However, dendrites of DA neurones also ramify close to the neuropil of non-dopaminergic reticulata neurones in SN. The question has arisen whether dendritically release DA might also influence these neurones which, to a large extent, project to ventromedial thalamus (VM) and superior colliculus. A necessary condition would be that they are sensitive to DA. In the experiments reported here this was found to be the case--a considerable proportion of nigrothalamic neurones were activated by iontophoretically applied DA. This contrasts with its known depressant effect on pars compacta DA neurones which we confirmed.

Action Potentials↗
PubMed1979

Proximal limb movements in response to microstimulation of primate dentate and interpositus nuclei mediated by brain-stem structures.

The cerebellar dentate and interpositus nuclei and the area of their efferent fibres have been stimulated in Cebus monkeys, using a movable microcathode. Responses consisted of eye and face movements and a stereotyped flexion of proximal parts of extremities. Very few distal limb movements were seen. The activation of proximal muscles was studied most closely. It consisted of the limited number of 5 movements: arm flexion and shoulder elevation in the forelimb and hip flexion, knee flexion and dorsiflexion of the ankle in the hindlimb. With currents of up to 100 microamperemeter these movements were elicited more readily from the interpositus and the area of efferent fibres of both nuclei as compared to the dentate nucleus. Responses were more often seen in forelimb than in hindlimb muscles, without apparent somatotopy in either nucleus. Combined forelimb-hindlimb movements were elicited from 42 per cent of effective points. Lesions placed at various locations of cerebellar output pathways demonstrated that the responses were mediated by the descending branch of brachium conjunctivum and did not require the activation of structures anterior to and including the red nucleus. The responses are interpreted to represent adjustments in flexor posture that may serve to modify maintained antigravity tonus during the initiation of volitional movements. This function, mediated by brain-stem structures, is considered to be closely associated with the activity of the lateral and intermediate cerebellum during initiation and conduction of volitional movements, which is mediated mainly through the cerebral cortex. It is stressed that control over both flexor posture and discrete distal movements is inherent in the initiation of voluntary movements.

Animals↗
PubMed1978

Short-term increase and long-term reversion of striatal cell activity after degeneration of the nigrostriatal dopamine system.

The spontaneous activity of neurons in the head of the striatum was studied in rats 3 days and more than 1 year after a 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine system in comparison to unlesioned animals. Cells were detected and tracked by stimulating the excitatory corticostriatal pathway. In unlesioned animals striatal cells discharged at very low frequencies, with a median of 0.04 impulse/second. The activity was increased to 0.28 impulses/second 3 days after the lesion. This increase was related to the degree of dopamine depletion. More than 1 year after the lesion, the frequency had decreased to a level indistinguishable from that measured in unlesioned animals, with a median of 0.03 impulses/second. Cells in 3-day lesioned animals discharged a higher number of bursts at shorter intervals as compared to unlesioned animals, while in long-term denervated animals the bursting pattern was similar to that in unlesioned animals. This demonstrates that removal of the dopaminergic input results in increased activity only during an initial phase and that adaptive processes subsequently occur. The data from this Parkinsonian model suggest that symptoms of this disease cannot simply be related to an increased striatal cellular activity. The fact that the initially increased spontaneous activity adapted indicates that functional effects of a lesion can only be evaluated when studying the resulting changes throughout a time course.

Action Potentials↗