L. Larochelle

The nigrostriatal pathway: a correlative study based on neuroanatomical and neurochemical criteria in the cat and the monkey.

Abstract Localized lesions of the corpus striatum result in a regional cell loss in the ipsilateral substantia nigra. Unilateral lesions of the ventromedial tegmental area (Tsai) in the upper midbrain or caudal hypothalamus result in a complete cell loss in the corresponding substantia nigra and nucleus parabrachialis pigmentosus. The latter morphological changes are associated with a decreased concentration of dopamine in the ipsilateral corpus striatum. Lesions of the rostrolateral hypothalamus involving the region of the medial forebrain bundle (MFB) produce similar morphological and chemical changes. Caudolateral lesions of the substantia nigra result in a decreased concentration of dopamine in the laterocaudal part of the corpus striatum corresponding to the caudal putamen. The interruption of the striatonigral fibers does not produce any cell change in the substantia nigra. Lesions of the entopeduncular nucleus or of the ventral thalamus do not produce any cell change in the substantia nigra and are associated with a normal concentration of dopamine in the corpus striatum. These results suggest that the nigrostriatal fibers establish a topographical relationship between corresponding regions of the substantia nigra and the corpus striatum similar to that disclosed in the striatonigral pathway. This striato-nigro-striatal loop represents a peculiar mechanism involved in the synthesis of striatal dopamine.

The rubro-olivo-cerebello-rubral loop and postural tremor in the monkey.

Abstract The interruption of the rubro-olivary (from the small-celled red nucleus) or olivocerebellar fibres or of the superior cerebellar peduncle or destruction in the area of the lateral cerebellar nuclei did not result in any important and sustained motor impairment. The injection of harmaline following the interruption of the olivocerebellar (before their crossing) or rubro-olivary fibres induces postural tremor in the contralateral limbs. The injection of harmaline following lesions of the superior cerebellar peduncle or the interruption of the olivocerebellar fibres (after their crossing) or lesions in the area of the lateral cerebellar nuclei induces postural tremor in the ipsilateral limbs. It is concluded that the interruption of the rubro-olivo-cerebello-rubral loop and its interconnections represents an important feature in the appearance of postural tremor. Sustained postural tremor, however, will appear only after the concomitant involvement of certain upper brain stem monoaminergic mechanisms, a disturbance which is apparently duplicated by the effect of harmaline.

Parkinsonian akinesia, rigidity and tremor in the monkey

Parkinsonian postural tremor and rigidity most likely involve the disruption of the dopaminergic (DA) nigrostriatal mechanisms and the corresponding rubro-olivo-cerebello-rubral loop without excluding the involvement of related dentato-rubral and dentato-thalamic nervous fascicles. The integrity of the magnocellular division of the red nucleus and of the rubrotegmentospinal pathway, however, is apparently essential for the expression of rigidity. Akinesia most likely results from the bilateral involvement of brain stem catecholaminergic (CA) mechanisms including the DA nigrostriatal pathways. Finally the integrity of the pallidothalamic fibers seems to represent an essential feature for the improvement of these motor disorders by DA agonists, suggesting that certain of these agents, such as apomorphine, exert their main effects through the neostriatal DA receptors.

Correlative neuroanatomical and neuropharmacological study of tremor and catatonia in the monkey

Abstract A parkinson-like tremor of the limbs in monkeys with certain brain lesions results from the combined involvement of the rubro-olivo-cerebello-rubral loop and the corresponding nigrostriatal dopaminergic mechanism. The interruption of the dopaminergic mechanism may be pharmacologically duplicated by the administration of α-methyltyrosine, 3, α-dimethyltyrosine, α-methyldopa, thioproperazine or reserpine; these drugs induce postural tremor in monkeys with lesions of the rubral loop. Thioproperazine, reserpine and α-methyltyrosine given in sufficient amounts lead to a gradual decrease of locomotor activity, progressing to a catatonic state in the operated or unoperated monkeys. 3,4-dihydroxyphenylalanine has a transient, reversible effect on the tremor in lesioned monkeys and on the catatonia in unoperated animals when these states have been induced by α-methyltyrosine or reserpine. Apomorphine can rapidly alleviate reserpine-induced tremor. Benztropine also has a favourable effect on the tremor and catatonia induced in these ways, as well as on the thioproperazine-provoked motor impairments. Furthermore, the administration of apomorphine or d-amphetamine reverses the reserpine-induced catatonia and causes behavioral excitement. These facts underline the importance of both the impairment of dopaminergic fibers and the release of cholinergic mechanisms, especially at the level of the neostriatum, in the production of tremor, akinesia and catatonia. Akinesia and catatonia apparently depend on a more profound and generalized disturbance of dopamine metabolism than that associated with tremor. The production of tremor, however, involves the impairment of nervous mechanisms as well as those affected by the administered drug.

The effect of brain stem lesions on tyrosine and tryptophan hydroxylases in various structures of the telencephalon of the cat

Abstract Unilateral lesions of the ventromedial tegmental area of the upper brain stem are associated with decreased concentrations of tyrosine and tryptophan hydroxylases without any reduction of succinic dehydrogenase in different telencephalic structures on the corresponding side of the brain in the cat. Unilateral lesions of the intralaminar nuclei of the thalamus have no effect on the concentrations of any of these enzymes in the same tissues. These results indicate that the syntheses of dopamine and serotonin in the striatal and other tissues are dependent on the integrity of separate neuronal systems originating in specific cell groups of the brain stem.

Effect of dorsal rhizotomy on postural tremor in the monkey

SummaryRhizotomy of the dorsal roots of the upper limb in lesioned monkeys with lesioned-induced and harmaline-induced tremor caused complete anaesthesia and akinesia of the corresponding limb, which only showed purposeless movements. The rate and rhythm of postural tremor and the reciprocality of the bursts in opposite muscles were not affected by the rhizotomy; the incidence of tremor episodes was greater in some animals. Rhizotomy apparently interfered with the amplitude of the bursts which, at times, was less regular in the deafferented limb. In four out of six animals the rhizotomy involved the blood supply of the dorsal part of the lateral column. This caused a degeneration of the corresponding lateral corticospinal and dorsal spinocerebellar tracts, producing a weakness of the ipsilateral lower limb which gradually improved. Faster bursts (12–13/sec) were also noted on the EMG in response to harmaline in monkeys with cerebellar lesions.These findings suggest that the influence transmitted through the spinal dorsal roots does not play an important role in initiating postural tremor. The rate and rhythm of tremor episodes are uninfluenced by impulses transmitted through the dorsal roots which, however, apparently exert a stabilizing effect on the amplitude of the bursts.

Brain nervous mechanisms involved in the so-called extra pyramidal motor and psychomotor disturbances.

2.3. The striopallidal (extrapyramidal) system 2.1.1. Outline of structures 2.1.2. Intrinsic nervous connections 2.1.3. Distribution of extrinsic nervous fascicles (outflow) 2.1.4. Relationship to thalamus, motor cortex and’cerebellofugal ascending nervous pathways The rubro-olivo-cerebella-rubral loop 2.2.1. Outline of structures 2.2.2. “Intrinsic” nervous connections 2.2.3. Distribution of extrinsic nervous fascicles (outflow) 2.2.4. Relationship to thalamus, striopallidal system, motor cortex and certain brain stem relay nuclei Brain stem relay nuclei and descending pathways 2.3.1. Rubrotegmentospinal tract 2.3.2. Vestibulospinal nervous pathways 2.3.3. Reticulospinal nervous pathways

Haloperidol-Induced Dyskinesias in the Monkey

Haloperidol (0.25 mg/kg i.m.) was injected daily for 6 months in six normal monkeys. Over a 24 hour period, the following symptoms could be observed: akathisia, circling, akinesia, choreoathetoid and dystonic movements, oro-facial dyskinesias and postural tremor with or without harmaline. Six months after cessation of haloperidol, harmaline-induced postural tremor could still be observed in all animals and oro-facial abnormal movements, in one monkey. The neuropathologic study of the experimental material did not disclose any alteration of the central nervous system.

Physiopathology of the cerebellum in the monkey ☆: Part 2. Motor disturbances associated with partial and complete destruction of cerebellar structures

Abstract Profound truncal ataxia, dysmetria, postural tremor of the head, trunk and limbs and hypotonia and intention (acting) tremor of the limbs were displayed by 3 monkeys with total cerebellectomy and 2 monkeys with extensive damage to several structures of the cerebellum. Truncal ataxia, dysmetria, hypotonia and intention tremor gradually diminished during the immediate postoperative period whereas postural tremor became less conspicuous. The administration of harmaline, however, exaggerated or evoked postural tremor of the limbs and trunk for a period of 3–4 hr in these monkeys. On the one hand lesions of the vermis of the posterior lobe and of part of the nodulus in one animal or of the interpositus and fastigial nuclei of both sides and the nodulus in another animal or destruction of the uvula and the interpositus nuclei associated with partial involvement of dentate and fastigial nuclei of both sides in a third animal resulted in truncal ataxia and transient dysmetria. The latter animal repeatedly displayed postural tremor of the two upper limbs in response to harmaline. Harmaline, however, did not produce any peculiar effect in the 2 former animals. On the other hand unilateral or bilateral lesions of the dentate and interpositus nuclei or destruction of the left half of the posterior lobe (with or without involvement of the corresponding dentate nucleus) or interruption of the superior cerebellar peduncle did not result in any marked and/or sustained motor impairment. Nine out of 10 monkeys with such lesions, however, displayed postural tremor of the ipsilateral limbs after the administration of harmaline. Truncal ataxia predominantly involves a disturbance of the uvula and nodulus and/or the fastigial nuclei and their interconnections with the vestibular nuclei and, most likely, with the dorsal and medial accessory olives. Dysmetria (or incoordination of the limbs) is apparently related to a combined impairment of structures of the anterior and posterior lobes of the cerebellum and their corresponding interconnections with the cerebellar nuclei. Postural tremor is partly related to a disturbance at the level of a series of phylogenetically more recent structures including parts of the principal olive, neocerebellar cortex and dentate nucleus and the parvocellular division of the red nucleus as well as their nervous interconnections.

Effect of section of the strionigral fibers on dopamine turnover in the forebrain of the rat

Abstract Haloperidol accelerates the turnover of dopamine in the nigrostriatal dopaminergic system. Since haloperiodol blocks the striatal dopamine receptors, the acceleration could be mediated through a neuronal feedback system, namely, the cholinesterase-containing strionigral fibers. After interruption of the latter fibers however, there is no suppression of the haloperidol induced increase in homovanillic acid in the striatum of the rat. In intact animals, arecoline does not mimic the effect of haloperidol on the homovanillic acid content of the striatum.