Lesions of the substantia nigra in the rhesus monkey. Efferent fiber degeneration and behavioral observations

Abstract

While neuropathological studies have indicated that the substantia nigra is one of the principal neural structures affected with a high degree of consistency in paralysis agitans (Brissaud, 1895; Trktiakoff, '19; Foix, '21; Spatz, '27; Hassler, '39; Timmer, '40; Heath, '47), relatively few experimental studies have contributed information concerning the physiological function of this large mesencephalic nucleus. Data concerning the anatomical connections of this nucleus appear incomplete even though numerous descriptions of pathways to and from the substantia nigra have been reported in the literature. The efferent fibers of the substantia nigra are the least understood because it has been technically difficult to produce localized lesions in this nucleus in experimental animals. Studies of nigral efferent fibers based upon lesions in this nucleus have utilized the Marchi method (Ranson and Ranson, '42; Mettler, '42, '43; Kimmel, '42; Rosegay, '44) which because of inherent limitations cannot be considered conclusive (Bowsher, Brodal and Walberg, '60). The objects of the current study of the substantia nigra in the monkey were to determine: ( 1 ) the course and distribution of nigral efferent fibers, and ( 2 ) what physiological disturbances, if any, are associated with discrete lesions in this nucleus. MATERIAL AND METHODSTwenty-six rhesus monkeys were used in this study. In these animals attempts were made to produce discrete unilateral and bilateral lesions in the substantia nigra by stereotaxic techniques. Coordinate S~S L tems for this procedure were developed from dissections of formalin fixed heads with brains in situ (Carpenter and Whittier, '52). Two different stereotaxic approaches were used in producing these lesions: ( 1 ) a frontal approach, in which electrodes were introduced into the brain in parasagittal planes in nearly the rostrocaudal axis of the substantia nigra, and (2) a lateral approach, in which electrodes were inserted in the lateromedial axis of the substantia nigra. These different coordinate systems were used because it was realized that the passage of electrodes through adjacent neural structures and concomitant destruction of parts of neighboring nuclei would make it difficult to evaluate the fiber degeneration resulting from nigral lesions.Animals were anesthetized with Nembutal intravenously and surgery was performed aseptically. Following the insertion of the electrode according to the adopted coordinate system, stimulating square wave currents of low voltage were applied in attempts to confirm the position of the electrode tip. Physiological effects produced by these stimulations were recorded. At what appeared to be optimal locations, lesions were produced by a direct current of 3 ma and 400 volts applied for intervals of 15 seconds. When attempts were made to produce lesions in the rostrocaudal axis of the substantia nigra, four separate lesions were made serially at 1 mm intervals along a single electrode track. Two electrode placements usually were made 2 mm apart, at the s...

Quantitative Registration of Motor Disorders following Bilateral Lesions of Substantia nigra in the Rat

“…Other investigators have correlated experimentally induced tremor with the interruption of cerebellar efferents [2,3,19]. However, bilateral lesions in the nigra of monkeys consistently induce hypokinesia, which is characterized by a lack of spontaneous motor activity and decreased locomation [1,6,19]. In cats, we observed a comparable akinesia and ipsilateral circling move ment after complete unilateral lesions in the area of the nigra [21].…”

“…These experimental re sults have been controversial. Discrete lesions in the nigra of the monkey have had no effect on motor behavior [1], Some investigators have pro duced Parkinson-like tremor by making lesions in the midbrain tegmen tum dorsomedial to the substantia nigra [6,15,16]. Other investigators have correlated experimentally induced tremor with the interruption of cerebellar efferents [2,3,19].…”

Caudate nucleus neurones: correlation of the effects of substantia nigra stimulation with iontophoretic dopamine

“…, 1965(Anden et at. , 1966a, efferent nigral projections to thalamic, pallidal, and tegmental areas have been described using silver impregnation techniques (Carpenter & McMasters, 1964;Afifi & Kaelber, 1965). It is apparent therefore that even very specific nigral stimuli could affect caudate neurones by one or more polysynaptic pathways as well as by activation of the direct dopaminergic projection.…”

Enhancement of Apomorphine-Induced Rotational Behaviour in Rats Following the Combination of 6-Hydroxydopamine and Electrolytic Lesions in the Substantia Nigra

“…The function of the strionigral fiber was inhibitory (23), and the transmitter was suggested to be GABA (24). The efferent pathways from the SN were found to be nigrostriatal fiber which contained DA (25)(26)(27), nigropallidal fiber (28) and nigrotegmental fiber (29) and the latter was mainly transmitted at the midbrain reticular formation and descended to the motor neuron in the anterior horn of the spinal cord. The injection of 6-OHDA into the area of the SN relatively selec tively degenerated the nigrostriatal dopaminergic neurons, while the electrolytic lesion impaired not only the nigrostriatal dopaminergic pathway but also afferent and efferent pathways as described above in the SN region.…”