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The corticorubral projection in the cat further observations
EXPERIMENTAL
NEUROLOGY
The
12,
2’78-291
(1965)
Corticorubral Further
Projection Observations ERIC
Anatomical
Institute, Received
in the
Cat
RINVIK
University February
of Oslo, Oslo, Norway 1, 1965
The distribution of terminal degeneration within the red nucleus following lesions of various parts of the cerebral cortex was studied in the cat with silver methods. A few degenerating terminal fibers were found in the nucleus when the lesion was restricted to the gyrus proreus, supplementary motor area, or secondary sensory area. The majority of corticofugal fibers originating from these cortical regions terminated on the soma or proximal dendrites of cells of all sizes in the nucleus. The findings substantiate earlier observations of a homolateral corticorubral connection in the cat. In addition, a few crossed corticorubral fibers were found, but only following lesions limited to the supplementary motor area and possibly the gyrus proreus. Lesions of the remaining parts of the lateral aspect of the cerebral cortex revealed no terminal degeneration in the red nucleus. Introduction
The corticorubral projection from coronal, precruciate and postcruciate gyri in the cat was determined in a previous study (26). It was shown that the fibers originating from the primary motor area in the cat project heavily upon the ipsilateral red nucleus, and that this fiber system is somatotopically organized. The hindlimb and forelimb areas of the cat’s primary motor cortex project onto those regions of the ipsilateral red nucleus which send their fibers to the lumbar and cervical segmentsof the spinal cord, respectively, (23, 24). The present study was undertaken to investigate whether other cortical regions contribute to the corticorubral projection in the cat. Material
and
Methods
Lesions were made of different parts of the cerebral cortex in fourteen cats under Nembutal anesthesiawith a knife and suction. The animalswere killed by an overdose of Nembutal, and most cats were perfused intravitally with
10 per cent formalin
3-8 days after the operation.
dissected and immersed in 10 per cent formalin. 278
The brain was
CORTICORUBRAL
PROJECTION
279
The lesion in the cerebral cortex was mapped macroscopically, and the whole brain was cut in serial frontal sections on the freezing microtome at 15 or 20 p. The sections were collected in groups of fifteen or twenty, and some from each group were impregnated with the silver methods of Nauta (18, 19). In some, the method of Glees (7) was used as well. Sections from the part of the brain containing the lesion were also stained with thionine or cresyl-violet to identify more exactly the extent and the depth of the lesions and to check whether subcortical structures had been damaged. I. S.S.
CSJ.c.p. rw
s.. -
0 A
e.s.
e.
1.P
s.
v.a.s.p.
S.S. Tp.
FIG. 1. Diagrams of the cerebral cortex of the cat. A and B show the lateral and medial aspects of the hemisphere, respectively. C is adapted from Woolsey (31) and shows the outlines of the areas related to “specific” cortical functions. Abbreviations: Aud. I, primary auditory area; Aud. II, secondary auditory area; c.a., anterior cruciate gyrus; c.p., posterior cruciate gyrus; ci., gyrus cinguli; car., gyrus coronalis; e.s., ectosylvian gyrus; e.s.a., anterior ectosylvian gyrus; e.s.p., posterior ectosylvian gyrus; l., gyrus lateralis; I.p., gyrus lateralis posterior; M I, primary motor area; M II, supplementary motor area; pr., gyrus proreus; S I, primary sensory area; S II, secondary sensory area; s, sylvian gyrus; s.a., anterior sylvian gyrus; s.p., posterior sylvian gyrus ; spl., gyrus splenialis; s.s., suprasylvian gyrus; s.s.a., anterior suprasylvian gyrus; s.s.p., posterior suprasylvian gyrus; s.spl., gyrus suprasplenialis; vis. I, primary visual area; vis. II, secondary visual area.
280
RINVIK
Drawings of the silver impregnated sections were made with a projection apparatus. The distribution of finer and coarser degenerating fibers observed under the microscope was entered in the drawings as dots and wavy lines, respectively. Woolsey’s map (31, Fig. IC) of the cat’s cortex was used for identification of cortical areas. Observations
Large Lesion of One Hemisphere. A left hemidecortication was attempted in one cat which was then killed after 5 days (Fig. 2A). The gyrus cinguli and the caudal and ventral parts of the splenial gyrus on the medial aspect of the hemisphere as well as the tip of the temporal lobe escaped involvement. Microscopical examination showed that the adjacent subcortical white matter had been damaged to some extent without, however, involving the subcortical gray structures. The cerebral cortex of the right hemisphere was intact. Abundant terminal degeneration was seen in the ipsilateral red nucleus and mesencephalic reticular formation. l Most degenerating terminal fibers were found in the neuropil of the nucleus, but many made contact with the soma or proximal dendrites of cells of all sizes. In addition, some degenerating terminal fibers were found in the contralateral red nucleus, most of them close to cell somata and processes. On neither side were the degenerating terminal fibers restricted to a particular area of the red nucleus. This was in contrast to the findings in the ipsilateral mesencephalic reticular formation where most of the degenerating terminal fibers were close to the dorsolateral border of the rostra1 part of the nucleus. The amount of degeneration in the contralateral red nucleus was markedly less than on the ipsilateral side. Because of their small number, it was difficult t? decide where these fibers crossed the midline. Many were seen in the corpus callosum, but very few in the internal capsule contralateral to the lesion. At mesencephalic levels no degenerating fiber crossed the midline ventral to the aqueduct. This case clearly shows that the cerebral cortex of the cat, in addition to a heavy projection onto the ipsilateral red nucleus, sends some fibers to the contralateral nucleus. Since no such crossed fibers were seen following lesions of the cat’s primary sensory-motor cortex (26), other cortical regions must project upon the contralateral and possibly the ipsilateral red nuclei. 1 Only the reticularformationadjacentto the red nucleushasbeenstudied.
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281
342
FIG. 2. Diagrams of the experimental
showing animals.
the lesions (hatchings) For details see text.
of the left
hemisphere
in some
282
RINVIK
Lesion of Primary and Secondary Auditory Areas. In one animal, killed after 6 days, the lesion was in the sylvian, ectosylvian and posterior e&osylvian gyri of the lefmthemisphere (Fig. 2B), involving the primary and secondary auditory areas (3 1) . Microscopical examination showed that the adjacent subcortical matter had been damaged wi,thout, however, involving the basal ganglia. No degenerated fiber was seen in the red nucleus of either side. The same negative finding was made in another cat (not illustrated) with a lesion restricted to the primary auditory area. Lesion of Primary and Secondary Visual Areas. The lesion involved the caudal part of the lateral and suprasylvian gyri and the posterior lateral gyrus on the lateral aspect of the left cerebral hemisphere and the caudal half of the suprasplenial gyrus on the medial aspect in a cat which was killed after 3 days (Fig. 2C). This corresponds to the primary and secondary visual areas (31). Adjacent subcortical white matter had been damaged, and the basal ganglia were intact. In none of the sections from the mesencephalon were degenerating fibers seen in the red nuclei. In another, killed after 7 days (not illustrated), a similarly placed but smaller lesion gave the same negative result. Lesion of Parietal Cortex. The lesion in a cat killed after 7 days (Fig. 2D) was in ,the left hemisphere in the parts of the suprasylvian and lateral gyri which lie between the primary sensory, secondary visual, and primary auditory areas (Fig. 1C). On the medial aspect of the left hemisphere it involved the rostra1 part of the suprasplenial gyrus; although underlying white matter had been involved, the basal ganglia were unaffected. Both red nuclei were free from degeneration. Lesion of Secondary Sensory Area. A lesion in a cat killed after 7 days (Figs. 2E, 3A) involved the anterior ectosylvian gyrus, and thus included the secondary sensory and a small rostra1 part of the secondary auditory areas. The basal ganglia were intact, and adjacent subcortical white matter was slightly involved. Some terminal degenerating fibers were seen throughout lthe ipsilateral red nucleus, more evident in the dorsolateral region of the rostra1 part. At this level the mesencephalic reticular formation adjacent to the ipsilateral red nucleus was particularly rich in degenerating terminal fibers. Many lay close to the soma or dendrites of the red nucleus (Fig. 3A). However, none was seen in the contralateral nucleus or mesencephalic reticular formation. Corresponding observations were made after 5 days in another cat (not illustrated) with a practically identical lesion. Lesion of Supplementary Motor Area. A small lesion was made in the
CORTICORUBRAL
PROJECTION
FIG. 3. Photomicrographs showing degenerating ter in various cases, Nauta method. A, dorsolateral regic red nucleus in cat B.St.L. 275 (X 530). Arrows indical from contralateral red nucleus in cat B.St.L. 379 (X lateral red nucleus in the same animal (D and F, X indicates degenerating fiber. Note the intimate relatio fibers and cell somata and dendrites.
283
,minal fibers in the red nucleus m of rostra1 part of ipsilateral :e degenerating fibers. B and C, 1300) ; D, E and F, from ipsi530; E, x 1300). Arrow in D nship between the degenerating
284
RINVIK
anterior cruciate gyrus on the medial aspect of the left cerebral hemisphere (Figs. 2F, 3B-F). This, theoretically in the cat, correspondsto the supplementary motor area in the monkey and man (3 1) . Microscopical examination revealed that underlying white matter had been slightly encroached upon, and the basal ganglia were intact. The corresponding region of the right hemispherewas undamaged. Degenerating terminal fibers were seen in the ipsilateral and contralateral red nuclei ; in the former they outnumbered those in ‘the latter. Some few degenerating fibers were seen in the contralateral internal capsule at rostra1 levels, but could not be followed with certainty farther caudally. The degenerating fibers were not localized to special regions within the red nucleus but were evenly distributed throughout it. The majority of degenerating terminal fibers in both nuclei were applied to somaor proximal dendrites of cells of all sizes (Fig. 3B-F). Corresponding findings were made in other cats with practically identical lesions (two killed after 8 days, and one, after 6 days). Lesion of the Cyrus Proreus. In a cat killed after 7 &ys (Figs. 2G, 4D), the lesion was restricted to the lateral and medial aspects of the gyrus proreus of the left hemisphere.This gyrus in the cat is generally considered as the homologof the frontal lobe rostra1 to area IV in higher forms. Microscopical examination revealed that adjacent subcortical white matter, basal ganglia, and medial aspect of the right cerebral hemispherewere undamaged. Degenerating terminal fibers were seenin both red nuclei, much more ipsilaterally ‘than contralaterally and evenly distributed throughout, lying close to soma or proximal dendrites of cells of all sizes. This was more evident ipsilaterally, probably because of the very small number of degenerating fibers in the contralateral red nucleus. Very few were seenin the contralateral internal capsule. Corresponding findings were made in two other cats killed after 6 (Fig. 4A-C) and 7 days, where the gurus proreus alone was damaged.
FIG. 4. Photomicrographs showing terminal degenerating fibers in the red nucleus in two cases with lesion of the gyrus proreus, Nauta method. A and B, ipsilateral red nucleus in cat B.St.L. 378 (A, X 1300; B, X 530). Arrows in A indicate one degenerating fiber part of which is out of focus. Due to shrinkage there is a cleft between the degenerating terminal fiber and cell soma. C, contralateral red nucleus in same animal (X 1300) ; D, ipsilateral red nucleus in cat B.St.L. 381 (X 800). Arrow indicates degenerating fiber. Note the intimate relationship between the degenerating fibers and the soma and proximal dendrites of cells.
CORTICORUBRAL
PROJECTION
28.5
286
RINVIK Discussion
A direct corticorubral tract has been demonstrated in various animals with Marchi (11, 13, 15, 29) and Nauta methods (8, 10). Its existence in man has been shown with the Glees (17) and Marchi (14) stains. The earlier investigations in man were with pathological material where, following more or less extensive lesions of the cerebral cortex, secondary atrophy in the red nuclei was studied. Most experimental investigations on a direct corticorubral pathway in animals have been undertaken by the Marchi method with which unmyelinated degenerating fibers as well as terminal nerve endings escape recognition. The present method of choice, the Nauta technique, actually may stain degenerating terminal fibers as well as “preterminal” ones (9, 3O), but Glees’ stain is often necessary to identify degenerating boutons with certainty.2 Therefore, I used it to obtain supplementary information. Origin of Corticorubral Fibers. The origin of corticorubral fibers has been a matter of dispute and controversy, especially among investigators using human pathological material. Most agree that the sensory-motor area and more frontal regions of the cerebral cortex are major contributors to this fiber system. In the present study no degenerating terminal fibers were seen in the red nucleus following lesions of primary and secondary visual areas, primary and secondary auditory areas, the tip of the temporal lobe and the parietal cortex lying between the primary sensory area and secondary auditory areas. Pearce (2 1) studied corticomesencephalic projections, and his drawings do not indicate terminal degeneration in the red nuclei following lesions of the auditory cortex and visual area. On the other hand, my study shows that the gyrus proreus and the medial aspect of the anterior cruciate gyrus (supplementary motor area) contribute to the cat’s corticorubral projection system (Figs. 3B-F; 4A, B, D). Whether the secondary sensory area is an independent contributor as well is more difficult to decide. Lesions restricted to this cortical region resulted in a few scattered degenerating terminal fibers in the ipsilateral red nucleus. However, they were concentrated in the dorsolateral part of the nucleus at rostra1 levels and in the mesencephalic reticular formation adjacent to this part of the red nucleus (Fig. 3A). The same pattern of 2 In Nauta sections the boutons are often compact and may therefore be mistaken for fragments of degenerating terminal fibers. Furthermore, only occasionally can a “tail” be seen in connection with a bouton in Nauta material, whereas this is more often observed by Glees’ stain.
CORTICORUBRAL
PROJECTION
287
localization was seen following lesions restricted to the primary sensory area, i.e., posterior cruciate gyrus (26). Since the lesions of the somatic area II invariably damaged the adjacent subcortical white matter to some degree, they may have interrupted fibers coming from the more medially placed posterior cruciatus gyrus. However, the anterior ectosylvian gyrus itself may send fibers to the red nucleus and mesencephalic reticular formation, because the few degenerating terminal fibers in the red nucleus following a lesion of the somatic area II were often close to the somata of cells and their proximal dendrites. This was not seen in cases with lesions restricted ,to the primary sensory area. In such cases the few degenerating corticorubral fibers were seen to end in the neuropil of the ipsilateral red nucleus (26). Crossed and Uncrossed Corticorubral Fibers. Whether the corticorubral projection is crossed or uncrossed had not been settled previously. Rinvik and Walberg (26) concluded that the pathway in the cat is homolateral, because the massive degeneration following lesions of the lateral part of the anterior cruciate gyrus was confined to the ipsilateral nucleus. In no case with lesions of the primary sensory-motor cortex were degenerating fibers observed in the contralateral red nucleus. In the present study, however, lesions of the gyrus proreus and the medial aspect of the anterior cruciate gyrus (supplementary motor area) gave rise to degenerating terminal fibers in both red nuclei. The supplementary motor area sent more fibers to the ipsilateral and contralateral red nuclei than did the gyrus proreus, and the number in both instances was less in the contralateral nucleus than in the ipsilateral, indeed, so small that it may be considered negligible in the contralateral red nucleus. A greater part of the gyrus proreus lies on the medial aspect of the cerebral hemisphere and, moreover, ventral to the supplementary motor area. I cannot exclude the possibility that the gyrus sends no fibers at all to the homolateral red nucleus, but that a lesion of this gyrus may damage some fibers coming from the dorsally situated supplementary motor area which has been shown to project onto the red nucleus of both sides. However, the cases with lesions of the supplementary motor area show that the fibers from this region do not descend close to the gray matter of the gyrus proreus but take a rostrocaudal course. Therefore, it is unlikely that a lesion of the gyrus proreus will interrupt the corticofugal fibers from the dorsally and slightly more caudally situated supplementary motor area. Probably both these cortical areas contribute to the corticorubral projection. It has not been established with certainty where the corticofugal fibers
288
RINVIK
to the contralateral red nucleus cross the midline. Drawings of Szentigothai and Rajkovits (28), who investigated the frontofugal fibers in the cat, indicate degenerating fibers which leave the cerebral peduncle and cross the midline at mesencephalic levels ventral to the aqueduct. Such fibers were never observed in the present study, but a few were seen in the contralateral internal capsule. Perhaps crossed corticorubral fibers pass by way of the corpus callosum and contralateral internal capsule. One might not expect the supplementary motor area or the gyrus proreus to project to the ipsilateral and contralateral red nuclei, whereas the more impressive corticorubral contingent coming from the primary motor area is strictly homolateral, but a lesion of the medial aspect of the left cerebral hemisphere may secondarily affect the corresponding cortical region of the right hemisphere. However, in none of the present cases was there any damage to the right cerebral cortex. Termination of Corticorubral Fibers. Following lesions restricted to either the gyrus proreus or the supplementary motor area, the ensuing degenerating terminal fibers in the red nucleus were seen close to cell somata and processes. Rinvik and Walberg (26) did not find this true following lesions of the primary motor area; most of the degenerating terminal fibers in the red nucleus were in the neuropil. This is indicative of an elaborate and differential cortical influence on the red nucleus. I have found the same mode of termination in the substantia nigra after lesions of the supplementary motor area and the gyrus proreus (25). The corticonigral fibers which originate from these two cortical areas are uncrossed as well as crossed, and most of the scanty degenerating terminal fibers in the substantia nigra are seen close to the somata or proximal dendrites of the nigra cells. This parallelism leads me to speculate that there is a functional relationship between the supplementary motor area and gyrus proreus, on the one hand, and these two mesencephalic nuclear structures, on the other hand. Functional Considerations. The possible significance of the corticorubrospinal pathway in relation to the preserved capacity to perform “skilled voluntary movements” following section of the corticospinal fibers in the cerebral peduncle in man and monkeys (4-6) has been discussed elsewhere (3, 26). Woolsey (3 1) suggested that the supplementary motor area probably lies on the medial aspect of the anterior cruciate gyrus in the cat. Hughes (12) conducted a physiologic study in which he reported two felunculi on the cat’s mesial cortex, one located anteriorly and the other more poste-
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289
PROJECTION
riorly. Bilateral movements, especially of the face and head, followed stimulation of the cortical areas where the two felunculi are located. This bilaterality was more evident following stimulation of the posterior felunculus, while the anterior one showed a heavier contralateral representation. On the other hand, the threshold for eliciting movements was lower for the anterior felunculus than for the posterior one. Hughes’ map of the cat’s hemisphere shows the greater part of the anterior felunculus on the mesial aspect of the anterior cruciate gyrus. I have shown that this region projects upon both red nuclei and more abundantly on the ipsilateral than the contralateral nucleus. Since the rubrospinal tract is completely crossed (20, 24), impulses from the supplementary motor area may chiefly reach the opposite side of the body by way of the corticorubrospinal projection system. Furthermore, the demonstration that the corticorubral fibers from the supplementary motor area terminate on the cell somata and proximal dendrites may explain the low threshold in obtaining muscular movements by stimulating this cortical area (12). A direct crossed and uncrossed corticospinal pathway from the supplementary motor area appears to be present in the cat (Nyberg-Hansen, personal communication). This observation further emphasizes the similarity in the anatomical organization of the corticospinal and corticorubrospinal pathways in this animal. Physiological studies on the mesencephalon in the cat have shown that the red nucleus exerts a facilitatory influence on the flexor muscle groups (1, 2, 22, 23, 27), while the reticular formation adjacent to the dorsolateral part of the nucleus contributes to a sustained extensor rigidity in animals decerebrated at a precollicular level ( 16). The present findings and those reported previously by Rinvik and Walberg (26) show that the corticofugal fibers in ,the cat which terminate in the red nucleus and in the mesencephalic reticular formation take origin from different areas of the cerebral cortex. References 1.
APPELBERG,
B.
1962a.
The
the gamma motor system. 2.
3.
4.
5.
effect
Acta
of
electrical stimulation of nucleus ruber on
Physiol.
Stand.
56:
150-159.
stimulation
in nucleus ruher on the response to stretch in primary and secondary muscle spindle afferents. Acta Physiol. Stand. 56: 140-151. BRODAL, A. 1962. Some anatomical considerations of the corticospinal tract and corticofugal fibres to the brain stem. Acute Hemiplegia in Childhood. Little Club C&z. Develop. Med. 6: 24-36. BUCY, P. C. 1957. Is there a pyramidal tract? Brain 60: 376-392. BUCY, P. C., and J. E. KEPLINGER. 1961. Section of the cerebral peduncles. Arch. Neural. 5: 132-139.
APPELBERG,
B.
1962b.
The
effect
of
electrical
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P. C., J. E. KEPLINGER, and E. B. SIQUEIRA. 1964. Destruction of the “pyramidal tract” in man. J. Neurosurg. 21: 385-398. GLEES, P. 1946. Terminal degeneration within the central nervous system as studied by a new silver-method. J. Neuropath. Exptl. Newel. 5: 54-59. GROFOVA, I. 1964. Experimental demonstration of frontorubral connections in the cat, pp. 107.113. In “Experimental Embryology and Neuroanatomy.” Publishing House of Czechoslovak Acad. Sci., Prague. 1964. Nerve fibers and terminals: elecR. W., and H. J. RALSTON. 9. GUILLERY, tron microscopy after Nauta staining. Science 143: 1331-1332. Projections to Mesencephalon, Pons, Medulla IO. HAARTSEN, A. B. 1962. “Cortical Oblongata and Spinal Cord. An Experimental Study in the Goat and the Rabbit.” Thesis (128 pp.). Eduard Ijdo N.V., Leiden. 11. HIRASAWA, K., and K. KATO. 1935. ijber die Fasern, insbesondere die corticalen extrapyramidalen aus den Areae 8 (u, p, y, 6) und 9 (c, d) der Grosshirnrinde beim Affen. Folia Anat. Japon. 13: 189-217. mesial cortex of unanaesthe12. HUGHES, J. R. 19.59. Studies of the supracallosal tired, conscious mammals. I. Cat. A. Movements elicited by electrical stimulation. Electroencephalog. Clin. Neurophysiol. 11: 447-458. 13. IGARASI, Y. 1940. Uber die Faserverbindung des vorderen Theiles der lateralen Grosshirnhemispharenfhache bei der Ziege. Gegenbuurs Morph. Jb. 94: 108-153. 14. KANKI, S., and T. BAN. 1952. Cortico-fugal connections of frontal lobe in man. Med. J. Osaka Univ. 3: 201-222. 1936. Experimentelle Untersuchung iiber die cortikalen extrapyra1.5. KARIYA, K. midalen Fasern aus dem sog. motorischen Rindenzentrum (Area 4 und 6) der Katze. Folia Anat. Japon. 14: 241-297. 16. MAFFEI, L., and 0. POMPEIANO. 1962. Effects of stimulation of the mesencephalic tegmentum following interruption of the rubrospinal tract. Arch. It&. Biol. 100: 510-525. BUCY,
17. 18.
19.
20.
21.
22.
MEYER, brain
M. 1949. Study of efferent connexions of the frontal lobe in the human after leucotomy. Bruin 72: 265-296. NAUTA, W. J. H. 1957. Silver impregnation of degenerating axons, pp. 17-26. In “New Research Techniques of Neuroanatomy.” W. F. Windle led.]. Thomas, Springfield, Illinois. NAUTA, W. J. H., and P. A. GYGAX. 1954. Silver impregnation of degenerating axons in the central nervous system: a modified technique. Stain Technol. 29: 91-93. NYBERG-HANSEN, R., and A. BRODAL. 1964. Sites and mode of termination of rubrospinal fibres in the cat. An experimental study with silver impregnation methods. 1. Anat. 98: 235-253. PEARCE, G. W. 1960. Some cortical projections to the midbrain reticular formation, pp. 131-137. In “Structure and Function of the Cerebral Cortex.” D. B. Tower and I. P. Schade leds.1. Proceedings of the Second International Meeting of Neurobiologists, Amsterdam, 1959. POMPEIANO, 0. 1956. Sulle risposte postura!i alla stimolazione elettrica de1 nucleo rosso nel gatto decerebrato. Boll. Sot. Ital. Biol. Sper. 32: 1450-1451.
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24. 25. 26.
27.
28.
29. 30.
31.
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0. 1957. Analisi degli effetti della stimolazione elettrica de1 nucleo rosso nel gatto decerebrato. Atti Accad. Nazi. Lincei, Rend-Classe Sci. Fis. Mat. Nat. 22: 100-103. POMPEIANO, O., and A. BRODAL. 1957. Experimental demonstration of a somatotopical origin of rubrospinal fibers in the cat. J. Camp. Neural. 108: 225-251. RINVIK, E. 1965. The cortico-nigral projection in the cat. An experimental study with silver impregnation methods. J. Camp. Neural. (in press). RINVIK, E., and F. W.~LBERG. 1963. Demonstration of a somatotopically arranged cortico-rubral projection in the cat. An experimental study with silver methods. J. Comp. Neural. 120: 393-407. SASAKI, K., A. NAMIKAWA, and S. HASHIRAMOTO. 1960. The effect of midbrain stimulation upon alpha motoneurons in lumbar spinal cord of the cat. Japan. J. Physiol. 10: 303-316. 1958. Der Hirnnervenanteil der PyraSZENTAGOTHAI, J,, and K. RAJKOVITS. midenbahn und der prLmotorische Apparat motorischer Hirnnervenkerne. Arch. Psychiat. Nervenkrankh. 197: 335-354. UCHISHIMA, S. 1936. ijber die corticalen extrapyramidalen Fasern aus der Area 8 der Grosshirnrinde der Katze. Z. Mikroskop.-Anat. Forsch. 40: 541-557. WALBERC, F. 1964. The early changes in degenerating boutons and the problem of argyrophilia. Light and electron microscopic observations. J. Comp. Newel. 122: 113-137. WOOLSEY, C. x. 1958. Organization of somatic sensory and motor areas of the cerebral cortex, pp. 63-81. In “Biological and Biochemical Bases of Behavior.” H. F. Harlow and C. N. Woolsey reds.]. Univ. of Wisconsin Press, Madison. Wisconsin.
POMPEIANO,
NEUROLOGY
The
12,
2’78-291
(1965)
Corticorubral Further
Projection Observations ERIC
Anatomical
Institute, Received
in the
Cat
RINVIK
University February
of Oslo, Oslo, Norway 1, 1965
The distribution of terminal degeneration within the red nucleus following lesions of various parts of the cerebral cortex was studied in the cat with silver methods. A few degenerating terminal fibers were found in the nucleus when the lesion was restricted to the gyrus proreus, supplementary motor area, or secondary sensory area. The majority of corticofugal fibers originating from these cortical regions terminated on the soma or proximal dendrites of cells of all sizes in the nucleus. The findings substantiate earlier observations of a homolateral corticorubral connection in the cat. In addition, a few crossed corticorubral fibers were found, but only following lesions limited to the supplementary motor area and possibly the gyrus proreus. Lesions of the remaining parts of the lateral aspect of the cerebral cortex revealed no terminal degeneration in the red nucleus. Introduction
The corticorubral projection from coronal, precruciate and postcruciate gyri in the cat was determined in a previous study (26). It was shown that the fibers originating from the primary motor area in the cat project heavily upon the ipsilateral red nucleus, and that this fiber system is somatotopically organized. The hindlimb and forelimb areas of the cat’s primary motor cortex project onto those regions of the ipsilateral red nucleus which send their fibers to the lumbar and cervical segmentsof the spinal cord, respectively, (23, 24). The present study was undertaken to investigate whether other cortical regions contribute to the corticorubral projection in the cat. Material
and
Methods
Lesions were made of different parts of the cerebral cortex in fourteen cats under Nembutal anesthesiawith a knife and suction. The animalswere killed by an overdose of Nembutal, and most cats were perfused intravitally with
10 per cent formalin
3-8 days after the operation.
dissected and immersed in 10 per cent formalin. 278
The brain was
CORTICORUBRAL
PROJECTION
279
The lesion in the cerebral cortex was mapped macroscopically, and the whole brain was cut in serial frontal sections on the freezing microtome at 15 or 20 p. The sections were collected in groups of fifteen or twenty, and some from each group were impregnated with the silver methods of Nauta (18, 19). In some, the method of Glees (7) was used as well. Sections from the part of the brain containing the lesion were also stained with thionine or cresyl-violet to identify more exactly the extent and the depth of the lesions and to check whether subcortical structures had been damaged. I. S.S.
CSJ.c.p. rw
s.. -
0 A
e.s.
e.
1.P
s.
v.a.s.p.
S.S. Tp.
FIG. 1. Diagrams of the cerebral cortex of the cat. A and B show the lateral and medial aspects of the hemisphere, respectively. C is adapted from Woolsey (31) and shows the outlines of the areas related to “specific” cortical functions. Abbreviations: Aud. I, primary auditory area; Aud. II, secondary auditory area; c.a., anterior cruciate gyrus; c.p., posterior cruciate gyrus; ci., gyrus cinguli; car., gyrus coronalis; e.s., ectosylvian gyrus; e.s.a., anterior ectosylvian gyrus; e.s.p., posterior ectosylvian gyrus; l., gyrus lateralis; I.p., gyrus lateralis posterior; M I, primary motor area; M II, supplementary motor area; pr., gyrus proreus; S I, primary sensory area; S II, secondary sensory area; s, sylvian gyrus; s.a., anterior sylvian gyrus; s.p., posterior sylvian gyrus ; spl., gyrus splenialis; s.s., suprasylvian gyrus; s.s.a., anterior suprasylvian gyrus; s.s.p., posterior suprasylvian gyrus; s.spl., gyrus suprasplenialis; vis. I, primary visual area; vis. II, secondary visual area.
280
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Drawings of the silver impregnated sections were made with a projection apparatus. The distribution of finer and coarser degenerating fibers observed under the microscope was entered in the drawings as dots and wavy lines, respectively. Woolsey’s map (31, Fig. IC) of the cat’s cortex was used for identification of cortical areas. Observations
Large Lesion of One Hemisphere. A left hemidecortication was attempted in one cat which was then killed after 5 days (Fig. 2A). The gyrus cinguli and the caudal and ventral parts of the splenial gyrus on the medial aspect of the hemisphere as well as the tip of the temporal lobe escaped involvement. Microscopical examination showed that the adjacent subcortical white matter had been damaged to some extent without, however, involving the subcortical gray structures. The cerebral cortex of the right hemisphere was intact. Abundant terminal degeneration was seen in the ipsilateral red nucleus and mesencephalic reticular formation. l Most degenerating terminal fibers were found in the neuropil of the nucleus, but many made contact with the soma or proximal dendrites of cells of all sizes. In addition, some degenerating terminal fibers were found in the contralateral red nucleus, most of them close to cell somata and processes. On neither side were the degenerating terminal fibers restricted to a particular area of the red nucleus. This was in contrast to the findings in the ipsilateral mesencephalic reticular formation where most of the degenerating terminal fibers were close to the dorsolateral border of the rostra1 part of the nucleus. The amount of degeneration in the contralateral red nucleus was markedly less than on the ipsilateral side. Because of their small number, it was difficult t? decide where these fibers crossed the midline. Many were seen in the corpus callosum, but very few in the internal capsule contralateral to the lesion. At mesencephalic levels no degenerating fiber crossed the midline ventral to the aqueduct. This case clearly shows that the cerebral cortex of the cat, in addition to a heavy projection onto the ipsilateral red nucleus, sends some fibers to the contralateral nucleus. Since no such crossed fibers were seen following lesions of the cat’s primary sensory-motor cortex (26), other cortical regions must project upon the contralateral and possibly the ipsilateral red nuclei. 1 Only the reticularformationadjacentto the red nucleushasbeenstudied.
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FIG. 2. Diagrams of the experimental
showing animals.
the lesions (hatchings) For details see text.
of the left
hemisphere
in some
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Lesion of Primary and Secondary Auditory Areas. In one animal, killed after 6 days, the lesion was in the sylvian, ectosylvian and posterior e&osylvian gyri of the lefmthemisphere (Fig. 2B), involving the primary and secondary auditory areas (3 1) . Microscopical examination showed that the adjacent subcortical matter had been damaged wi,thout, however, involving the basal ganglia. No degenerated fiber was seen in the red nucleus of either side. The same negative finding was made in another cat (not illustrated) with a lesion restricted to the primary auditory area. Lesion of Primary and Secondary Visual Areas. The lesion involved the caudal part of the lateral and suprasylvian gyri and the posterior lateral gyrus on the lateral aspect of the left cerebral hemisphere and the caudal half of the suprasplenial gyrus on the medial aspect in a cat which was killed after 3 days (Fig. 2C). This corresponds to the primary and secondary visual areas (31). Adjacent subcortical white matter had been damaged, and the basal ganglia were intact. In none of the sections from the mesencephalon were degenerating fibers seen in the red nuclei. In another, killed after 7 days (not illustrated), a similarly placed but smaller lesion gave the same negative result. Lesion of Parietal Cortex. The lesion in a cat killed after 7 days (Fig. 2D) was in ,the left hemisphere in the parts of the suprasylvian and lateral gyri which lie between the primary sensory, secondary visual, and primary auditory areas (Fig. 1C). On the medial aspect of the left hemisphere it involved the rostra1 part of the suprasplenial gyrus; although underlying white matter had been involved, the basal ganglia were unaffected. Both red nuclei were free from degeneration. Lesion of Secondary Sensory Area. A lesion in a cat killed after 7 days (Figs. 2E, 3A) involved the anterior ectosylvian gyrus, and thus included the secondary sensory and a small rostra1 part of the secondary auditory areas. The basal ganglia were intact, and adjacent subcortical white matter was slightly involved. Some terminal degenerating fibers were seen throughout lthe ipsilateral red nucleus, more evident in the dorsolateral region of the rostra1 part. At this level the mesencephalic reticular formation adjacent to the ipsilateral red nucleus was particularly rich in degenerating terminal fibers. Many lay close to the soma or dendrites of the red nucleus (Fig. 3A). However, none was seen in the contralateral nucleus or mesencephalic reticular formation. Corresponding observations were made after 5 days in another cat (not illustrated) with a practically identical lesion. Lesion of Supplementary Motor Area. A small lesion was made in the
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FIG. 3. Photomicrographs showing degenerating ter in various cases, Nauta method. A, dorsolateral regic red nucleus in cat B.St.L. 275 (X 530). Arrows indical from contralateral red nucleus in cat B.St.L. 379 (X lateral red nucleus in the same animal (D and F, X indicates degenerating fiber. Note the intimate relatio fibers and cell somata and dendrites.
283
,minal fibers in the red nucleus m of rostra1 part of ipsilateral :e degenerating fibers. B and C, 1300) ; D, E and F, from ipsi530; E, x 1300). Arrow in D nship between the degenerating
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anterior cruciate gyrus on the medial aspect of the left cerebral hemisphere (Figs. 2F, 3B-F). This, theoretically in the cat, correspondsto the supplementary motor area in the monkey and man (3 1) . Microscopical examination revealed that underlying white matter had been slightly encroached upon, and the basal ganglia were intact. The corresponding region of the right hemispherewas undamaged. Degenerating terminal fibers were seen in the ipsilateral and contralateral red nuclei ; in the former they outnumbered those in ‘the latter. Some few degenerating fibers were seen in the contralateral internal capsule at rostra1 levels, but could not be followed with certainty farther caudally. The degenerating fibers were not localized to special regions within the red nucleus but were evenly distributed throughout it. The majority of degenerating terminal fibers in both nuclei were applied to somaor proximal dendrites of cells of all sizes (Fig. 3B-F). Corresponding findings were made in other cats with practically identical lesions (two killed after 8 days, and one, after 6 days). Lesion of the Cyrus Proreus. In a cat killed after 7 &ys (Figs. 2G, 4D), the lesion was restricted to the lateral and medial aspects of the gyrus proreus of the left hemisphere.This gyrus in the cat is generally considered as the homologof the frontal lobe rostra1 to area IV in higher forms. Microscopical examination revealed that adjacent subcortical white matter, basal ganglia, and medial aspect of the right cerebral hemispherewere undamaged. Degenerating terminal fibers were seenin both red nuclei, much more ipsilaterally ‘than contralaterally and evenly distributed throughout, lying close to soma or proximal dendrites of cells of all sizes. This was more evident ipsilaterally, probably because of the very small number of degenerating fibers in the contralateral red nucleus. Very few were seenin the contralateral internal capsule. Corresponding findings were made in two other cats killed after 6 (Fig. 4A-C) and 7 days, where the gurus proreus alone was damaged.
FIG. 4. Photomicrographs showing terminal degenerating fibers in the red nucleus in two cases with lesion of the gyrus proreus, Nauta method. A and B, ipsilateral red nucleus in cat B.St.L. 378 (A, X 1300; B, X 530). Arrows in A indicate one degenerating fiber part of which is out of focus. Due to shrinkage there is a cleft between the degenerating terminal fiber and cell soma. C, contralateral red nucleus in same animal (X 1300) ; D, ipsilateral red nucleus in cat B.St.L. 381 (X 800). Arrow indicates degenerating fiber. Note the intimate relationship between the degenerating fibers and the soma and proximal dendrites of cells.
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28.5
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A direct corticorubral tract has been demonstrated in various animals with Marchi (11, 13, 15, 29) and Nauta methods (8, 10). Its existence in man has been shown with the Glees (17) and Marchi (14) stains. The earlier investigations in man were with pathological material where, following more or less extensive lesions of the cerebral cortex, secondary atrophy in the red nuclei was studied. Most experimental investigations on a direct corticorubral pathway in animals have been undertaken by the Marchi method with which unmyelinated degenerating fibers as well as terminal nerve endings escape recognition. The present method of choice, the Nauta technique, actually may stain degenerating terminal fibers as well as “preterminal” ones (9, 3O), but Glees’ stain is often necessary to identify degenerating boutons with certainty.2 Therefore, I used it to obtain supplementary information. Origin of Corticorubral Fibers. The origin of corticorubral fibers has been a matter of dispute and controversy, especially among investigators using human pathological material. Most agree that the sensory-motor area and more frontal regions of the cerebral cortex are major contributors to this fiber system. In the present study no degenerating terminal fibers were seen in the red nucleus following lesions of primary and secondary visual areas, primary and secondary auditory areas, the tip of the temporal lobe and the parietal cortex lying between the primary sensory area and secondary auditory areas. Pearce (2 1) studied corticomesencephalic projections, and his drawings do not indicate terminal degeneration in the red nuclei following lesions of the auditory cortex and visual area. On the other hand, my study shows that the gyrus proreus and the medial aspect of the anterior cruciate gyrus (supplementary motor area) contribute to the cat’s corticorubral projection system (Figs. 3B-F; 4A, B, D). Whether the secondary sensory area is an independent contributor as well is more difficult to decide. Lesions restricted to this cortical region resulted in a few scattered degenerating terminal fibers in the ipsilateral red nucleus. However, they were concentrated in the dorsolateral part of the nucleus at rostra1 levels and in the mesencephalic reticular formation adjacent to this part of the red nucleus (Fig. 3A). The same pattern of 2 In Nauta sections the boutons are often compact and may therefore be mistaken for fragments of degenerating terminal fibers. Furthermore, only occasionally can a “tail” be seen in connection with a bouton in Nauta material, whereas this is more often observed by Glees’ stain.
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localization was seen following lesions restricted to the primary sensory area, i.e., posterior cruciate gyrus (26). Since the lesions of the somatic area II invariably damaged the adjacent subcortical white matter to some degree, they may have interrupted fibers coming from the more medially placed posterior cruciatus gyrus. However, the anterior ectosylvian gyrus itself may send fibers to the red nucleus and mesencephalic reticular formation, because the few degenerating terminal fibers in the red nucleus following a lesion of the somatic area II were often close to the somata of cells and their proximal dendrites. This was not seen in cases with lesions restricted ,to the primary sensory area. In such cases the few degenerating corticorubral fibers were seen to end in the neuropil of the ipsilateral red nucleus (26). Crossed and Uncrossed Corticorubral Fibers. Whether the corticorubral projection is crossed or uncrossed had not been settled previously. Rinvik and Walberg (26) concluded that the pathway in the cat is homolateral, because the massive degeneration following lesions of the lateral part of the anterior cruciate gyrus was confined to the ipsilateral nucleus. In no case with lesions of the primary sensory-motor cortex were degenerating fibers observed in the contralateral red nucleus. In the present study, however, lesions of the gyrus proreus and the medial aspect of the anterior cruciate gyrus (supplementary motor area) gave rise to degenerating terminal fibers in both red nuclei. The supplementary motor area sent more fibers to the ipsilateral and contralateral red nuclei than did the gyrus proreus, and the number in both instances was less in the contralateral nucleus than in the ipsilateral, indeed, so small that it may be considered negligible in the contralateral red nucleus. A greater part of the gyrus proreus lies on the medial aspect of the cerebral hemisphere and, moreover, ventral to the supplementary motor area. I cannot exclude the possibility that the gyrus sends no fibers at all to the homolateral red nucleus, but that a lesion of this gyrus may damage some fibers coming from the dorsally situated supplementary motor area which has been shown to project onto the red nucleus of both sides. However, the cases with lesions of the supplementary motor area show that the fibers from this region do not descend close to the gray matter of the gyrus proreus but take a rostrocaudal course. Therefore, it is unlikely that a lesion of the gyrus proreus will interrupt the corticofugal fibers from the dorsally and slightly more caudally situated supplementary motor area. Probably both these cortical areas contribute to the corticorubral projection. It has not been established with certainty where the corticofugal fibers
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to the contralateral red nucleus cross the midline. Drawings of Szentigothai and Rajkovits (28), who investigated the frontofugal fibers in the cat, indicate degenerating fibers which leave the cerebral peduncle and cross the midline at mesencephalic levels ventral to the aqueduct. Such fibers were never observed in the present study, but a few were seen in the contralateral internal capsule. Perhaps crossed corticorubral fibers pass by way of the corpus callosum and contralateral internal capsule. One might not expect the supplementary motor area or the gyrus proreus to project to the ipsilateral and contralateral red nuclei, whereas the more impressive corticorubral contingent coming from the primary motor area is strictly homolateral, but a lesion of the medial aspect of the left cerebral hemisphere may secondarily affect the corresponding cortical region of the right hemisphere. However, in none of the present cases was there any damage to the right cerebral cortex. Termination of Corticorubral Fibers. Following lesions restricted to either the gyrus proreus or the supplementary motor area, the ensuing degenerating terminal fibers in the red nucleus were seen close to cell somata and processes. Rinvik and Walberg (26) did not find this true following lesions of the primary motor area; most of the degenerating terminal fibers in the red nucleus were in the neuropil. This is indicative of an elaborate and differential cortical influence on the red nucleus. I have found the same mode of termination in the substantia nigra after lesions of the supplementary motor area and the gyrus proreus (25). The corticonigral fibers which originate from these two cortical areas are uncrossed as well as crossed, and most of the scanty degenerating terminal fibers in the substantia nigra are seen close to the somata or proximal dendrites of the nigra cells. This parallelism leads me to speculate that there is a functional relationship between the supplementary motor area and gyrus proreus, on the one hand, and these two mesencephalic nuclear structures, on the other hand. Functional Considerations. The possible significance of the corticorubrospinal pathway in relation to the preserved capacity to perform “skilled voluntary movements” following section of the corticospinal fibers in the cerebral peduncle in man and monkeys (4-6) has been discussed elsewhere (3, 26). Woolsey (3 1) suggested that the supplementary motor area probably lies on the medial aspect of the anterior cruciate gyrus in the cat. Hughes (12) conducted a physiologic study in which he reported two felunculi on the cat’s mesial cortex, one located anteriorly and the other more poste-
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riorly. Bilateral movements, especially of the face and head, followed stimulation of the cortical areas where the two felunculi are located. This bilaterality was more evident following stimulation of the posterior felunculus, while the anterior one showed a heavier contralateral representation. On the other hand, the threshold for eliciting movements was lower for the anterior felunculus than for the posterior one. Hughes’ map of the cat’s hemisphere shows the greater part of the anterior felunculus on the mesial aspect of the anterior cruciate gyrus. I have shown that this region projects upon both red nuclei and more abundantly on the ipsilateral than the contralateral nucleus. Since the rubrospinal tract is completely crossed (20, 24), impulses from the supplementary motor area may chiefly reach the opposite side of the body by way of the corticorubrospinal projection system. Furthermore, the demonstration that the corticorubral fibers from the supplementary motor area terminate on the cell somata and proximal dendrites may explain the low threshold in obtaining muscular movements by stimulating this cortical area (12). A direct crossed and uncrossed corticospinal pathway from the supplementary motor area appears to be present in the cat (Nyberg-Hansen, personal communication). This observation further emphasizes the similarity in the anatomical organization of the corticospinal and corticorubrospinal pathways in this animal. Physiological studies on the mesencephalon in the cat have shown that the red nucleus exerts a facilitatory influence on the flexor muscle groups (1, 2, 22, 23, 27), while the reticular formation adjacent to the dorsolateral part of the nucleus contributes to a sustained extensor rigidity in animals decerebrated at a precollicular level ( 16). The present findings and those reported previously by Rinvik and Walberg (26) show that the corticofugal fibers in ,the cat which terminate in the red nucleus and in the mesencephalic reticular formation take origin from different areas of the cerebral cortex. References 1.
APPELBERG,
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in nucleus ruher on the response to stretch in primary and secondary muscle spindle afferents. Acta Physiol. Stand. 56: 140-151. BRODAL, A. 1962. Some anatomical considerations of the corticospinal tract and corticofugal fibres to the brain stem. Acute Hemiplegia in Childhood. Little Club C&z. Develop. Med. 6: 24-36. BUCY, P. C. 1957. Is there a pyramidal tract? Brain 60: 376-392. BUCY, P. C., and J. E. KEPLINGER. 1961. Section of the cerebral peduncles. Arch. Neural. 5: 132-139.
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P. C., J. E. KEPLINGER, and E. B. SIQUEIRA. 1964. Destruction of the “pyramidal tract” in man. J. Neurosurg. 21: 385-398. GLEES, P. 1946. Terminal degeneration within the central nervous system as studied by a new silver-method. J. Neuropath. Exptl. Newel. 5: 54-59. GROFOVA, I. 1964. Experimental demonstration of frontorubral connections in the cat, pp. 107.113. In “Experimental Embryology and Neuroanatomy.” Publishing House of Czechoslovak Acad. Sci., Prague. 1964. Nerve fibers and terminals: elecR. W., and H. J. RALSTON. 9. GUILLERY, tron microscopy after Nauta staining. Science 143: 1331-1332. Projections to Mesencephalon, Pons, Medulla IO. HAARTSEN, A. B. 1962. “Cortical Oblongata and Spinal Cord. An Experimental Study in the Goat and the Rabbit.” Thesis (128 pp.). Eduard Ijdo N.V., Leiden. 11. HIRASAWA, K., and K. KATO. 1935. ijber die Fasern, insbesondere die corticalen extrapyramidalen aus den Areae 8 (u, p, y, 6) und 9 (c, d) der Grosshirnrinde beim Affen. Folia Anat. Japon. 13: 189-217. mesial cortex of unanaesthe12. HUGHES, J. R. 19.59. Studies of the supracallosal tired, conscious mammals. I. Cat. A. Movements elicited by electrical stimulation. Electroencephalog. Clin. Neurophysiol. 11: 447-458. 13. IGARASI, Y. 1940. Uber die Faserverbindung des vorderen Theiles der lateralen Grosshirnhemispharenfhache bei der Ziege. Gegenbuurs Morph. Jb. 94: 108-153. 14. KANKI, S., and T. BAN. 1952. Cortico-fugal connections of frontal lobe in man. Med. J. Osaka Univ. 3: 201-222. 1936. Experimentelle Untersuchung iiber die cortikalen extrapyra1.5. KARIYA, K. midalen Fasern aus dem sog. motorischen Rindenzentrum (Area 4 und 6) der Katze. Folia Anat. Japon. 14: 241-297. 16. MAFFEI, L., and 0. POMPEIANO. 1962. Effects of stimulation of the mesencephalic tegmentum following interruption of the rubrospinal tract. Arch. It&. Biol. 100: 510-525. BUCY,
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M. 1949. Study of efferent connexions of the frontal lobe in the human after leucotomy. Bruin 72: 265-296. NAUTA, W. J. H. 1957. Silver impregnation of degenerating axons, pp. 17-26. In “New Research Techniques of Neuroanatomy.” W. F. Windle led.]. Thomas, Springfield, Illinois. NAUTA, W. J. H., and P. A. GYGAX. 1954. Silver impregnation of degenerating axons in the central nervous system: a modified technique. Stain Technol. 29: 91-93. NYBERG-HANSEN, R., and A. BRODAL. 1964. Sites and mode of termination of rubrospinal fibres in the cat. An experimental study with silver impregnation methods. 1. Anat. 98: 235-253. PEARCE, G. W. 1960. Some cortical projections to the midbrain reticular formation, pp. 131-137. In “Structure and Function of the Cerebral Cortex.” D. B. Tower and I. P. Schade leds.1. Proceedings of the Second International Meeting of Neurobiologists, Amsterdam, 1959. POMPEIANO, 0. 1956. Sulle risposte postura!i alla stimolazione elettrica de1 nucleo rosso nel gatto decerebrato. Boll. Sot. Ital. Biol. Sper. 32: 1450-1451.
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