EXPERIMENTAL
NEUROLOGY
46, dog-417 (1975)
The Projection of Occipital Cortex to the Dorsal Lateral Geniculate Nucleus in the Rhesus Monkey (Macaca L. A. BENEVENTO College of Medicine,
University
of Received
Mulatta) l AND JAMES H. FALLON
Illinois
Medical
September
Center,
Chicago,
Illinois
60680
30,1974
Large lesions were made in the occipital cortex of rhesus monkeys and the subsequent degeneration in the dorsal lateral geniculate nucleus was analyzed with the Fink-Heimer technique. Evidence was found for both anterograde and retrograde degeneration in the dorsal lateral geniculate nucleus. Moderately dense pericellular and terminal degeneration was found in all layers of the dorsal lateral geniculate nucleus. In addition, in all layers of the dorsal lateral geniculate nucleus, some cells undergoing retrograde degeneration exhibited a Fink-Heimer positive argyrophilia that was interpreted as being different from the argyrophilia associated with anterograde degeneration. It is concluded that the occipital cortex projects to the dorsal lateral geniculate nucleus in the rhesus monkey.Theseresultsare consistent with the reports for other primate and nonprimate species that show a direct projection from the occipital cortex to the dorsal lateral geniculate
nucleus. INTRODUCTION Corticothalamic connections have been studied extensively in the visual system of various mammals. Using the neuroanatomical techniques of Marchi and Nauta, a number of authors have found evidence for a projection from the visual cortex to the dorsal lateral geniculate nucleus in the opossum (3, 23), rat (13, 24, 26, 33), cat (6, 11, 12, 14-16, 27), bushbaby (8), squirrel monkey (35) and rhesus monkey (7, 21, 25, 29). In addition, electron microscopic examinations have provided evidence that the visual cortex projects to the dorsal lateral geniculate nucleus in the rat (22) and cat (2, 20, 32). Although a recent Nauta study failed (30) to 1 This study was supported by NSF Grant GB 35366X. J. H. Fallon was supported by NIMH training grant 8396. The technical assistance of Nodee DuBose in the preparation of the histological materials is greatly acknowledged. 409 Copyright All rights
0 1975 by Academic Press, Inc. of reproduction in any form reserved.
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FALLON
show a projection from striate cortex to the dorsal lateral geniculate nucleus in the squirrel monkey, an autoradiographic study has shown that there is a direct projection from visual cortex to this nucleus (17). Despite the neuroanatomical evidence for the projection of visual cortex to the dorsal lateral geniculate nucleus in the opossum, rat, cat, bushbaby and squirrel monkey, there is still some disagreement as to the existence of a projection from the visual cortex to this nucleus in the rhesus monkey (9). A major factor that has contributed to this disagreement has been the interpretation of argyrophilic degeneration with Nauta-type stains following ablation of the visual cortex. Since the dorsal lateral geniculate nucleus projects only to striate cortex in the rhesus monkey (IS), ablation of striate cortex may lead to retrograde changes of cells in the dorsal lateral geniculate nucleus. Furthermore, the cells undergoing retrograde degeneration in this nucleus may exhibit Nauta-positive argyrophilic properties (9, 28). Thus, it is important to exercise care in differentiating Nauta-positive retrograde and anterograde degeneration in the dorsal lateral geniculate nucleus following ablations of visual cortex. Since there is disagreement as to the existence of a corticogeniculate projection in the rhesus monkey, we investigated this question by making large lesions of visual cortex (areas OC, OB and OA of von Bonin and Bailey; areas 17, 18, 19 of Brodmann) and using the Fink-Heimer technique (10) for demonstrating degenerated axons and axon terminals. METHODS Three young, adult rhesus monkeys (2.4-4.5 kg) were used in the study. The animals were anesthetized with pentobarbital sodium (30 mg/kg ip) and lesions of occipital cortex were made by subpial aspirations under aseptic conditions. The cortical lesions were made in areas OC, OB, OA of von Bonin and Bailey (34)) corresponding generally to areas 17, 18 and 19 of Brodmann (Fig. 1) . At the end of the survival period ( 10, 14 or 16 days) the animals were anesthetized with pentobarbital sodium and perfused intracardially with 0.9% saline, followed by 10% formalin. The brains were blocked transversally in a stereotaxic plane and stored for two weeks in
FIG. 1. Reconstruction of lateral occipital lobe lesion. Abbreviations Lesion is illustrated in solid black.
(at left) and medial (at right) surfaces of sulci according to von Bonin and Bailey
of an (10).
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411
10% formalin. The brains were then placed in a 30% sucrose solution made with 10% formalin until the brains sank in the solution. Sections were cut in the transverse plane at 30 pm on a freezing microtome and were stained at 300 pm intervals with Procedure I of the Fink-Heimer technique (10). Other sections that were cut adjacent to the sections stained with the Fink-Heimer technique were stained by the cresyl violet technique. The pattern of degenerated fibers and associated “pericellular” and “terminal” degeneration was correlated with the cytoarchitectural features seen in the sections stained with cresyl violet. The method of plotting the degeneration, staining techniques and the interpretation of degeneration are described in detail elsewhere (4, 5). RESULTS The histological criteria of von Bonin and Bailey (34) were used to determine the extent of the unilateral occipital lobe lesions in three rhesus monkeys. In all three cases the lesions included all cortical layers of a majority of areas OC, OB and OA of the lateral, medial, superior and inferior surfaces of the occipital lobe, but the lesions did not include adjacent cortices outside of the occipital lobe. Figure 1 illustrates a reconstruction (from sections stained with cresyl violet) of one large occipital lobe lesion in areas OC, 013, and OA. Following the occipital lobe lesion, degenerated fibers were found to originate from the lesion site to distribute to the thalamus. In the present report, only the occipital lobe projections to the lateral geniculate nuclei will be described (Figs. 2 and 3). The degenerated fibers that were found to enter the lateral geniculate nuclei were of fine or medium caliber. Degenerated fibers terminated in two ways. “Terminal degeneration” was recorded when degenerated fibers led to, but not beyond what appeared to be their end ramifications consisting of small, irregular, spheroidal argyrophilic particles. This type of degeneration was characteristic of most degenerated axonal endings in the ventral lateral geniculate nucleus degeneration” was recorded when (pregeniculate nucleus). “Pericellular degenerated fibers exhibited frequent tortuous arrangments about, or in the vicinity of neuronal cell bodies. Moderately dense pericellular, and, to a lesser extent, terminal degeneration could be seen in the dorsal lateral geniculate nucleus (Fig. 4) following occipital lobe lesions. The pericellular and terminal degeneration that was seen in the dorsal and ventral lateral geniculate nuclei is illustrated in the three drawings of Fig. 3. In addition to the degeneration in the dorsal lateral geniculate nucleus that is typical of anterograde degenerative changes, another type of degeneration could also be seen in the dorsal lateral geniculate nucleus following the occipital lobe lesions. This type of degeneration was char-
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FIG. 2. Drawing of a transverse section of the diencephalon illustrating how degenerated fibers (short black lines) coursed into the dorsal lateral geniculate nucleus (DLGN) to give rise to moderately dense pericellular (large black dots) and terminal (small black dots) degeneration. The arrow points to an area of the dorsal lateral geniculate nucleus from which the photomicrographs of Fig. 4 were taken. Also illustrated is the claustrum (CLAUS), putamen (PUT), thalamic reticular nucleus (RET), tail of the caudate nucleus (CAUD) and inferior pulvinar (Pl>.
by Fink-Heimer (Nauta) positive cells (Fig. 5) as has been described in detail by Campos-Ortega et al. (9). The Fink-Heimer positive cells in the dorsal lateral geniculate nucleus were dark and usually exhibited a fragmented argyrophilic neuropil. These cells have been considered to have undergone retrograde degenerative changes that resulted
acterized
FIG. 3. Drawings of transverse sections of the dorsal lateral geniculate nucleus (DLGN) and ventral lateral geniculate nucleus (VLGN) illustrating moderately dense pericellular (large black dots) and terminal (small black dots) degeneration. Posterior level is at left, intermediate level is at center and anterior level is at right. The layers of the dorsal lateral geniculate nucleus are labeled l-6.
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FIG. 4. Photomicrographs of sections stained with the Fink-Heimer technique showing moderately dense pericellular and terminal degeneration in layer 1 of the dorsal lateral geniculate nucleus after a large occipital lobe lesion illustrated in Fig. 1. The area of the dorsal lateral geniculate nucleus from which these photomicrographs were taken is indicated by the arrow in Fig. 2. (A) Approx. X400, (B) Approx. x900.
from damage to their axons and axon terminations in the occipital lobe during the cortical lesions (9, 28). The photomicrograph in Fig. 5 demonstrates a typical Fink-Heimer positive cell that was seenin the dorsal lateral geniculate nucleus following an occipital lobe lesion.
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FIG. 5. Photomicrograph of a section stained with the Fink-Heimer technique showing a Fink-Heimer positive cell in the dorsal lateral geniculate nucleus after a large occipital lobe lesion illustrated in Fig. 1. (Approx. X600).
All types of degeneration described (pericellular and terminal degeneration as well as Fink-Heimer positive cells) could be seen in the dorsal lateral geniculate nucleus with 10, 14, and 16 day survival times. DISCUSSION Previous studies in the opossum (3, 23)) rat (13, 24, 26, 36) cat (6, 11, 12, 14-16, 27), bushbaby (8) and squirrel monkey (35) have reported a direct projection from the visual cortex to the dorsal lateral geniculate nucleus. The present results are also in agreement with early studies in the rhesus monkey (7, 21, 25, 29) that have reported a projection from the visual cortex to the dorsal lateral geniculate nucleus. More recently, however, Campos-Ortega et al. (9) studied degenerative changes in the dorsal lateral geniculate nucleus after ablation of visual cortex in the rhesus monkey using reduced silver staining techniques as well as electron microscopic examinations. Those authors (9) did not find evidence for direct efferents from any of the visual cortices to the dorsal lateral geniculate nucleus, but did find evidence of cells undergoing various stages of retrograde changes after lesions of area 17 (OC) of visual cortex. At the light microscopic level, these cells are recognized as Fink-Heimer (Nauta) positive and do not exhibit the “classic” argyrophilia that has been associated with anterograde (direct Wallerian) degeneration. In the present study we also found evidence of the Fink-Heimer positive cells (Fig. 5). However, we feel that
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we also have evidence for anterograde degeneration in the dorsal lateral geniculate nucleus after large lesions of visual cortex (Fig. 4). Previous authors (9, 28) have discussed in detail the need for careful interpretation of results gathered with reduced silver or electron microscopic techniques in trying to establish the presence or absence of direct reciprocal connections between the visual cortex and the dorsal lateral geniculate nucleus. In the present anatomical study with the Fink-Heimer stain, there is light microscopic evidence that both anterograde degenerative changes and retrograde changes are present in the dorsal lateral geniculate nucleus after lesions of the visual cortex. Campos-Ortega et al. (9) also found electron microscopic evidence that there are early signs of retrograde cell changes in the dorsal lateral geniculate nucleus after lesions of area 17 that were characterized by electron dense postsynaptic profiles indicative of degenerated dendrites and degenerated neuronal cell somata. After 5day survival times, degenerated axons were also seen. The degenerated axons were not interpreted as evidence for anterograde degeneration (which would indicate a direct projection from the visual cortex), but were interpreted as evidence for indirect Wallerian degeneration of axons of the dorsal lateral geniculate nucleus which might be expected at longer survival times after occipital cortex lesions. Hollgnder (16, 17) has stated the need for application of autoradiographic techniques to the problem of corticogeniculate connections. In a recent study Hollander (17) injected tritiated leucine into the deep cortical layers of striate cortex of the squirrel monkey and showed that there is a direct projection from the striate cortex to the dorsal lateral geniculae nucleus. Injections of tritiated leucine into the superficial layers (layers I-IV) of striate cortex did not result in radiographic labeling of diencephalic nuclei, including the dorsal lateral geniculate nucleus. In the present study, cortical lesions involved a significant amount of all layers of visual cortex and a direct projection to the dorsal lateral geniculate nucleus was seen. Thus, it is important that lesions in visual cortex include all cortical layers in order to demonstrate corticogeniculate connections. At the present time we are conducting autoradiographic studies using injections of tritiated leucine and proline into visual cortex of the rhesus monkey. Preliminary results of these autoradiographic studies have indicated a projection from visual cortex to the dorsal lateral geniculate nucleus. The results of the present report as well as preliminary findings with autoradiographic studies seem to indicate that a projection from visual cortex to the dorsal lateral geniculate nucleus in the rhesus monkey is similar to positive findings in other primate and nonprimate species. The function of this corticogeniculate projection in the rhesus monkey is not known. However, in the cat physiological evidence indicates that the
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projection from visual cortex to the dorsal lateral geniculate nucleus is involved in depolarization of retinogeniculate axons ( 1, 19, 31). REFERENCES 1. ANGEL, A., F. MAGNI, and D. STRATA. 1965. Evidence for presynaptic inhibition in the lateral geniculate body. Nature (London) 208 : 495-496. 2. BARRON, K. D., and P. F. DOOLIN. 1968. Ultrastructural observations on retrograde atrophy of lateral geniculate body II. The environs of the neuronal soma. J. Neuropath. Exp. Neural. 27 : 401-420. 3. BENEVENTO, L. A., and F. F. EBNER. 1970. Pretectal, tectal, retinal and cortical projections to thalamic nuclei of the opossum in stereotaxic coordinates. Brain Res. 18: 171-175. 4. BENEVENTO, L. A., and F. F. EBNER. 1971. The areas and layers of corticocortical terminations in the visual cortex of the Virginia opossum. J. Con@. Neural. 141: 157-190. 5. BENEVENTO, L. A., and F. F. EBNER. 1971. The contribution of the dorsal lateral geniculate nucleus to the total pattern of thalamic terminations in striate cortex of the Virginia opossum. J. Comb. Neural. 143: 243-260. 6. BERESFORD, W. A. 1961. Fibre degeneration following lesions of visual cortex of the cat, pp. 247-255. In “Neurophysiologic and Psychophysic des visuellen Systems.” R Jung and H. Kornhuber [Eds.]. Springer, Berlin. 7. BLACK, P., and R E. MYERS. 1962. Connections of the occipital lobe in monkey. Anat. Rec. 142 : 216-217. 8. CAMPOS-ORTEGA, J. A. 1968. Descending subcortical projections from the occipital lobe of Galago Crassicandatus, Exg. Neacrol. 21: 440-454. 9. CAMPOS-ORTEGA, J. A., W. R. HAYHOW, and P. F. DE V. CLUVER. 1970. The descending projections from the cortical visual fields of Macaca mulatta with particular reference to the question of a cortico-lateral geniculate pathway, Brain Behav. Evol. 3 : 368414. 10. FINK, R, and L. HEIMER. 1967. Two methods of selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system. Brain Res. 4 : 369-374. 11. GAREY, L. J. 1965. Interrelationships of the visual cortex and superior colliculus in the cat. Nature (London) 207: 1410-1411. 12. GAREY, L. J., E. G. JONES, and T. P. S. POWELL. 1968. Interrelationships of striate and extrastriate cortex with the primary relay sites of the visual pathway. I. Neurol. Neurosurg. Psychiat. 31: 135-157. 13. GOODMAN, D. C., and J. A. HOREL. 1966. Sprouting of optic tract projections in the brain stem of the rat, J. Comp. Neurol. 127 : 71-88. 14. GUILLERY, R W. 1967. Patterns of fiber degeneration in the dorsal lateral geniculate nucleus of the cat following lesions of the visual cortex. J. Con@. Neural. 130 : 197-222. 15. Houb;~n~a, H. 1970. The projection from the visual cortex to the lateral geniculate body (LGB) in experimental study with silver impregnation methods in the cat. Exg. Brain Res. 10: 219-235. 16. HOLLHNDER, H. 1972. Projection of the visual cortex to the lateral geniculate nucleus in the cat, pp. 475-484. 1% “Corticothalamic Projections and Sensorimotor Activities.” T. Frigyesi, E. Rinvik and M.D. Yahr ([Eds.]. Raven Press, New York.
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17. HOLL;~NDER, H. 1974. Projections from the striate cortex to the diencephalon in the squirrel monkey (Saimiri sciurcus) . A light microscopic radiographic study following intracortical injection of H” leucine. J. Camp. Neural. 155: 425-440. 18. HUBEL, D. H., and T. N. WIESEL. 1972. Laminar and columnar distribution of geniculo-cortical fibers in the macaque monkey. /. Camp. Neural. 146: 421450. 19. IWAMA, K., H. SAKAKURA, and T. KASAMATSU. 1965. Presynaptic inhibition in the lateral geniculate body induced by stimulation of the cerebral cortex. Jap .I. Physiol. 15 : 310-322. 20. JONES, E. G., and T. P. C. POWELL. 1969. An electron microscopic study of the mode of termination of corticothalamic fibres within the sensory relay nuclei of the thalamus, Proc. Roy. Sot. London Ser. B. 172 : 173-185. 21. KRIEG, W. J. S. 1%3. “Connections of the Cerebral Cortex. Brain Books, Evanston. 22. LUND, R. D. 1969. Fine structural changes within the dorsal lateral geniculate body of the rat following lesions of visual cortex. Anat. Rec. 163: p. 220. 23. MARTIN, G. 1968. The pattern of neocortical projections to the mesencephalon of the opossum. Brain Res. 11: 593-610. 24. MONTERO, V., and R. W. GUILLERY. 1968. Degeneration in the dorsal lateral geniculate of the rat following interruption of retinal or cortical connections. J. Camp. Nezlrol. 134 : 211-242. 25. MYERS, R. E. 1962. Striate cortex connections in the monkey. Fed. Proc. 21 : p. 352. 26. NAUTA, W. J. H., and V. M. BUCHER. 1954. Efferent connections of striate cortex in the albino rat. J. Camp. Neural. 100: 257-286. 27. NIIMI, K., S. KAWAMURA, and S. ISHIMARU. 1970. Anatomical organization of cortico-geniculate projections in the cat. Proc. Japan. Acad. 46: 878-$83. 28. NOBACK, C. R., 1972. Comments on the visual pathways, pp. 485-489. In “Corticothalamic Projections and Sensorimotor Activities.” T. Frigijesi, E. Rinvik, and M. D. Yahr [Eds.]. Raven Press, New York. 29. POLYAK, S. 1957. “The Vertebrate Visual System.” University of Chicago Press, Chicago, pp. 434-437. 30. SPATZ, W. B., J. TIGGES, and M. TIGGES. 1970. Subcortical projections, cortical associations, and some interlaminar connections of the striate cortex in the squirrel monkey. J. Camp. New&. 140 : 155-174. 31. SUZUKI, H., and E. KATZ. 1965. Cortically induced presynaptic inhibition in cat’s lateral geniculate body. Tohoku. J. Exp. Med. 86: 277-289. 32. SZENTAGOTHAI, J., J. HAMORI, and T. TOMBAL. 1966. Degeneration and electron microscope analysis of the synaptic glomeruli in the lateral geniculate body. Exp. Brain Res. 2 : 283 : 301. 33. VALVERDE, F. 1961. Conexiones cortico-talamicas y cortico-pretectales. Estudio experimental en la rata albina. An Anat. 10: 345-359. 34. VON BONIN, G., and P. BAILEY. 1947. “The Neocortex of Macaca Mulatta.” University of Illinois Press, Urbana. 35. WONGRILEY, M. T. T. 1972. Changes in the dorsal lateral geniculate nucleus of the squirrel monkey after unilateral ablation of the visual cortex. I. Comzp. Neural. 146 : 519-548.
NEUROLOGY
46, dog-417 (1975)
The Projection of Occipital Cortex to the Dorsal Lateral Geniculate Nucleus in the Rhesus Monkey (Macaca L. A. BENEVENTO College of Medicine,
University
of Received
Mulatta) l AND JAMES H. FALLON
Illinois
Medical
September
Center,
Chicago,
Illinois
60680
30,1974
Large lesions were made in the occipital cortex of rhesus monkeys and the subsequent degeneration in the dorsal lateral geniculate nucleus was analyzed with the Fink-Heimer technique. Evidence was found for both anterograde and retrograde degeneration in the dorsal lateral geniculate nucleus. Moderately dense pericellular and terminal degeneration was found in all layers of the dorsal lateral geniculate nucleus. In addition, in all layers of the dorsal lateral geniculate nucleus, some cells undergoing retrograde degeneration exhibited a Fink-Heimer positive argyrophilia that was interpreted as being different from the argyrophilia associated with anterograde degeneration. It is concluded that the occipital cortex projects to the dorsal lateral geniculate nucleus in the rhesus monkey.Theseresultsare consistent with the reports for other primate and nonprimate species that show a direct projection from the occipital cortex to the dorsal lateral geniculate
nucleus. INTRODUCTION Corticothalamic connections have been studied extensively in the visual system of various mammals. Using the neuroanatomical techniques of Marchi and Nauta, a number of authors have found evidence for a projection from the visual cortex to the dorsal lateral geniculate nucleus in the opossum (3, 23), rat (13, 24, 26, 33), cat (6, 11, 12, 14-16, 27), bushbaby (8), squirrel monkey (35) and rhesus monkey (7, 21, 25, 29). In addition, electron microscopic examinations have provided evidence that the visual cortex projects to the dorsal lateral geniculate nucleus in the rat (22) and cat (2, 20, 32). Although a recent Nauta study failed (30) to 1 This study was supported by NSF Grant GB 35366X. J. H. Fallon was supported by NIMH training grant 8396. The technical assistance of Nodee DuBose in the preparation of the histological materials is greatly acknowledged. 409 Copyright All rights
0 1975 by Academic Press, Inc. of reproduction in any form reserved.
410
BENEVENTO
AND
FALLON
show a projection from striate cortex to the dorsal lateral geniculate nucleus in the squirrel monkey, an autoradiographic study has shown that there is a direct projection from visual cortex to this nucleus (17). Despite the neuroanatomical evidence for the projection of visual cortex to the dorsal lateral geniculate nucleus in the opossum, rat, cat, bushbaby and squirrel monkey, there is still some disagreement as to the existence of a projection from the visual cortex to this nucleus in the rhesus monkey (9). A major factor that has contributed to this disagreement has been the interpretation of argyrophilic degeneration with Nauta-type stains following ablation of the visual cortex. Since the dorsal lateral geniculate nucleus projects only to striate cortex in the rhesus monkey (IS), ablation of striate cortex may lead to retrograde changes of cells in the dorsal lateral geniculate nucleus. Furthermore, the cells undergoing retrograde degeneration in this nucleus may exhibit Nauta-positive argyrophilic properties (9, 28). Thus, it is important to exercise care in differentiating Nauta-positive retrograde and anterograde degeneration in the dorsal lateral geniculate nucleus following ablations of visual cortex. Since there is disagreement as to the existence of a corticogeniculate projection in the rhesus monkey, we investigated this question by making large lesions of visual cortex (areas OC, OB and OA of von Bonin and Bailey; areas 17, 18, 19 of Brodmann) and using the Fink-Heimer technique (10) for demonstrating degenerated axons and axon terminals. METHODS Three young, adult rhesus monkeys (2.4-4.5 kg) were used in the study. The animals were anesthetized with pentobarbital sodium (30 mg/kg ip) and lesions of occipital cortex were made by subpial aspirations under aseptic conditions. The cortical lesions were made in areas OC, OB, OA of von Bonin and Bailey (34)) corresponding generally to areas 17, 18 and 19 of Brodmann (Fig. 1) . At the end of the survival period ( 10, 14 or 16 days) the animals were anesthetized with pentobarbital sodium and perfused intracardially with 0.9% saline, followed by 10% formalin. The brains were blocked transversally in a stereotaxic plane and stored for two weeks in
FIG. 1. Reconstruction of lateral occipital lobe lesion. Abbreviations Lesion is illustrated in solid black.
(at left) and medial (at right) surfaces of sulci according to von Bonin and Bailey
of an (10).
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10% formalin. The brains were then placed in a 30% sucrose solution made with 10% formalin until the brains sank in the solution. Sections were cut in the transverse plane at 30 pm on a freezing microtome and were stained at 300 pm intervals with Procedure I of the Fink-Heimer technique (10). Other sections that were cut adjacent to the sections stained with the Fink-Heimer technique were stained by the cresyl violet technique. The pattern of degenerated fibers and associated “pericellular” and “terminal” degeneration was correlated with the cytoarchitectural features seen in the sections stained with cresyl violet. The method of plotting the degeneration, staining techniques and the interpretation of degeneration are described in detail elsewhere (4, 5). RESULTS The histological criteria of von Bonin and Bailey (34) were used to determine the extent of the unilateral occipital lobe lesions in three rhesus monkeys. In all three cases the lesions included all cortical layers of a majority of areas OC, OB and OA of the lateral, medial, superior and inferior surfaces of the occipital lobe, but the lesions did not include adjacent cortices outside of the occipital lobe. Figure 1 illustrates a reconstruction (from sections stained with cresyl violet) of one large occipital lobe lesion in areas OC, 013, and OA. Following the occipital lobe lesion, degenerated fibers were found to originate from the lesion site to distribute to the thalamus. In the present report, only the occipital lobe projections to the lateral geniculate nuclei will be described (Figs. 2 and 3). The degenerated fibers that were found to enter the lateral geniculate nuclei were of fine or medium caliber. Degenerated fibers terminated in two ways. “Terminal degeneration” was recorded when degenerated fibers led to, but not beyond what appeared to be their end ramifications consisting of small, irregular, spheroidal argyrophilic particles. This type of degeneration was characteristic of most degenerated axonal endings in the ventral lateral geniculate nucleus degeneration” was recorded when (pregeniculate nucleus). “Pericellular degenerated fibers exhibited frequent tortuous arrangments about, or in the vicinity of neuronal cell bodies. Moderately dense pericellular, and, to a lesser extent, terminal degeneration could be seen in the dorsal lateral geniculate nucleus (Fig. 4) following occipital lobe lesions. The pericellular and terminal degeneration that was seen in the dorsal and ventral lateral geniculate nuclei is illustrated in the three drawings of Fig. 3. In addition to the degeneration in the dorsal lateral geniculate nucleus that is typical of anterograde degenerative changes, another type of degeneration could also be seen in the dorsal lateral geniculate nucleus following the occipital lobe lesions. This type of degeneration was char-
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FIG. 2. Drawing of a transverse section of the diencephalon illustrating how degenerated fibers (short black lines) coursed into the dorsal lateral geniculate nucleus (DLGN) to give rise to moderately dense pericellular (large black dots) and terminal (small black dots) degeneration. The arrow points to an area of the dorsal lateral geniculate nucleus from which the photomicrographs of Fig. 4 were taken. Also illustrated is the claustrum (CLAUS), putamen (PUT), thalamic reticular nucleus (RET), tail of the caudate nucleus (CAUD) and inferior pulvinar (Pl>.
by Fink-Heimer (Nauta) positive cells (Fig. 5) as has been described in detail by Campos-Ortega et al. (9). The Fink-Heimer positive cells in the dorsal lateral geniculate nucleus were dark and usually exhibited a fragmented argyrophilic neuropil. These cells have been considered to have undergone retrograde degenerative changes that resulted
acterized
FIG. 3. Drawings of transverse sections of the dorsal lateral geniculate nucleus (DLGN) and ventral lateral geniculate nucleus (VLGN) illustrating moderately dense pericellular (large black dots) and terminal (small black dots) degeneration. Posterior level is at left, intermediate level is at center and anterior level is at right. The layers of the dorsal lateral geniculate nucleus are labeled l-6.
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FIG. 4. Photomicrographs of sections stained with the Fink-Heimer technique showing moderately dense pericellular and terminal degeneration in layer 1 of the dorsal lateral geniculate nucleus after a large occipital lobe lesion illustrated in Fig. 1. The area of the dorsal lateral geniculate nucleus from which these photomicrographs were taken is indicated by the arrow in Fig. 2. (A) Approx. X400, (B) Approx. x900.
from damage to their axons and axon terminations in the occipital lobe during the cortical lesions (9, 28). The photomicrograph in Fig. 5 demonstrates a typical Fink-Heimer positive cell that was seenin the dorsal lateral geniculate nucleus following an occipital lobe lesion.
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FIG. 5. Photomicrograph of a section stained with the Fink-Heimer technique showing a Fink-Heimer positive cell in the dorsal lateral geniculate nucleus after a large occipital lobe lesion illustrated in Fig. 1. (Approx. X600).
All types of degeneration described (pericellular and terminal degeneration as well as Fink-Heimer positive cells) could be seen in the dorsal lateral geniculate nucleus with 10, 14, and 16 day survival times. DISCUSSION Previous studies in the opossum (3, 23)) rat (13, 24, 26, 36) cat (6, 11, 12, 14-16, 27), bushbaby (8) and squirrel monkey (35) have reported a direct projection from the visual cortex to the dorsal lateral geniculate nucleus. The present results are also in agreement with early studies in the rhesus monkey (7, 21, 25, 29) that have reported a projection from the visual cortex to the dorsal lateral geniculate nucleus. More recently, however, Campos-Ortega et al. (9) studied degenerative changes in the dorsal lateral geniculate nucleus after ablation of visual cortex in the rhesus monkey using reduced silver staining techniques as well as electron microscopic examinations. Those authors (9) did not find evidence for direct efferents from any of the visual cortices to the dorsal lateral geniculate nucleus, but did find evidence of cells undergoing various stages of retrograde changes after lesions of area 17 (OC) of visual cortex. At the light microscopic level, these cells are recognized as Fink-Heimer (Nauta) positive and do not exhibit the “classic” argyrophilia that has been associated with anterograde (direct Wallerian) degeneration. In the present study we also found evidence of the Fink-Heimer positive cells (Fig. 5). However, we feel that
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we also have evidence for anterograde degeneration in the dorsal lateral geniculate nucleus after large lesions of visual cortex (Fig. 4). Previous authors (9, 28) have discussed in detail the need for careful interpretation of results gathered with reduced silver or electron microscopic techniques in trying to establish the presence or absence of direct reciprocal connections between the visual cortex and the dorsal lateral geniculate nucleus. In the present anatomical study with the Fink-Heimer stain, there is light microscopic evidence that both anterograde degenerative changes and retrograde changes are present in the dorsal lateral geniculate nucleus after lesions of the visual cortex. Campos-Ortega et al. (9) also found electron microscopic evidence that there are early signs of retrograde cell changes in the dorsal lateral geniculate nucleus after lesions of area 17 that were characterized by electron dense postsynaptic profiles indicative of degenerated dendrites and degenerated neuronal cell somata. After 5day survival times, degenerated axons were also seen. The degenerated axons were not interpreted as evidence for anterograde degeneration (which would indicate a direct projection from the visual cortex), but were interpreted as evidence for indirect Wallerian degeneration of axons of the dorsal lateral geniculate nucleus which might be expected at longer survival times after occipital cortex lesions. Hollgnder (16, 17) has stated the need for application of autoradiographic techniques to the problem of corticogeniculate connections. In a recent study Hollander (17) injected tritiated leucine into the deep cortical layers of striate cortex of the squirrel monkey and showed that there is a direct projection from the striate cortex to the dorsal lateral geniculae nucleus. Injections of tritiated leucine into the superficial layers (layers I-IV) of striate cortex did not result in radiographic labeling of diencephalic nuclei, including the dorsal lateral geniculate nucleus. In the present study, cortical lesions involved a significant amount of all layers of visual cortex and a direct projection to the dorsal lateral geniculate nucleus was seen. Thus, it is important that lesions in visual cortex include all cortical layers in order to demonstrate corticogeniculate connections. At the present time we are conducting autoradiographic studies using injections of tritiated leucine and proline into visual cortex of the rhesus monkey. Preliminary results of these autoradiographic studies have indicated a projection from visual cortex to the dorsal lateral geniculate nucleus. The results of the present report as well as preliminary findings with autoradiographic studies seem to indicate that a projection from visual cortex to the dorsal lateral geniculate nucleus in the rhesus monkey is similar to positive findings in other primate and nonprimate species. The function of this corticogeniculate projection in the rhesus monkey is not known. However, in the cat physiological evidence indicates that the
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projection from visual cortex to the dorsal lateral geniculate nucleus is involved in depolarization of retinogeniculate axons ( 1, 19, 31). REFERENCES 1. ANGEL, A., F. MAGNI, and D. STRATA. 1965. Evidence for presynaptic inhibition in the lateral geniculate body. Nature (London) 208 : 495-496. 2. BARRON, K. D., and P. F. DOOLIN. 1968. Ultrastructural observations on retrograde atrophy of lateral geniculate body II. The environs of the neuronal soma. J. Neuropath. Exp. Neural. 27 : 401-420. 3. BENEVENTO, L. A., and F. F. EBNER. 1970. Pretectal, tectal, retinal and cortical projections to thalamic nuclei of the opossum in stereotaxic coordinates. Brain Res. 18: 171-175. 4. BENEVENTO, L. A., and F. F. EBNER. 1971. The areas and layers of corticocortical terminations in the visual cortex of the Virginia opossum. J. Con@. Neural. 141: 157-190. 5. BENEVENTO, L. A., and F. F. EBNER. 1971. The contribution of the dorsal lateral geniculate nucleus to the total pattern of thalamic terminations in striate cortex of the Virginia opossum. J. Comb. Neural. 143: 243-260. 6. BERESFORD, W. A. 1961. Fibre degeneration following lesions of visual cortex of the cat, pp. 247-255. In “Neurophysiologic and Psychophysic des visuellen Systems.” R Jung and H. Kornhuber [Eds.]. Springer, Berlin. 7. BLACK, P., and R E. MYERS. 1962. Connections of the occipital lobe in monkey. Anat. Rec. 142 : 216-217. 8. CAMPOS-ORTEGA, J. A. 1968. Descending subcortical projections from the occipital lobe of Galago Crassicandatus, Exg. Neacrol. 21: 440-454. 9. CAMPOS-ORTEGA, J. A., W. R. HAYHOW, and P. F. DE V. CLUVER. 1970. The descending projections from the cortical visual fields of Macaca mulatta with particular reference to the question of a cortico-lateral geniculate pathway, Brain Behav. Evol. 3 : 368414. 10. FINK, R, and L. HEIMER. 1967. Two methods of selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system. Brain Res. 4 : 369-374. 11. GAREY, L. J. 1965. Interrelationships of the visual cortex and superior colliculus in the cat. Nature (London) 207: 1410-1411. 12. GAREY, L. J., E. G. JONES, and T. P. S. POWELL. 1968. Interrelationships of striate and extrastriate cortex with the primary relay sites of the visual pathway. I. Neurol. Neurosurg. Psychiat. 31: 135-157. 13. GOODMAN, D. C., and J. A. HOREL. 1966. Sprouting of optic tract projections in the brain stem of the rat, J. Comp. Neurol. 127 : 71-88. 14. GUILLERY, R W. 1967. Patterns of fiber degeneration in the dorsal lateral geniculate nucleus of the cat following lesions of the visual cortex. J. Con@. Neural. 130 : 197-222. 15. Houb;~n~a, H. 1970. The projection from the visual cortex to the lateral geniculate body (LGB) in experimental study with silver impregnation methods in the cat. Exg. Brain Res. 10: 219-235. 16. HOLLHNDER, H. 1972. Projection of the visual cortex to the lateral geniculate nucleus in the cat, pp. 475-484. 1% “Corticothalamic Projections and Sensorimotor Activities.” T. Frigyesi, E. Rinvik and M.D. Yahr ([Eds.]. Raven Press, New York.
OCCIPITOGENICULATE
PROJECTION
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17. HOLL;~NDER, H. 1974. Projections from the striate cortex to the diencephalon in the squirrel monkey (Saimiri sciurcus) . A light microscopic radiographic study following intracortical injection of H” leucine. J. Camp. Neural. 155: 425-440. 18. HUBEL, D. H., and T. N. WIESEL. 1972. Laminar and columnar distribution of geniculo-cortical fibers in the macaque monkey. /. Camp. Neural. 146: 421450. 19. IWAMA, K., H. SAKAKURA, and T. KASAMATSU. 1965. Presynaptic inhibition in the lateral geniculate body induced by stimulation of the cerebral cortex. Jap .I. Physiol. 15 : 310-322. 20. JONES, E. G., and T. P. C. POWELL. 1969. An electron microscopic study of the mode of termination of corticothalamic fibres within the sensory relay nuclei of the thalamus, Proc. Roy. Sot. London Ser. B. 172 : 173-185. 21. KRIEG, W. J. S. 1%3. “Connections of the Cerebral Cortex. Brain Books, Evanston. 22. LUND, R. D. 1969. Fine structural changes within the dorsal lateral geniculate body of the rat following lesions of visual cortex. Anat. Rec. 163: p. 220. 23. MARTIN, G. 1968. The pattern of neocortical projections to the mesencephalon of the opossum. Brain Res. 11: 593-610. 24. MONTERO, V., and R. W. GUILLERY. 1968. Degeneration in the dorsal lateral geniculate of the rat following interruption of retinal or cortical connections. J. Camp. Nezlrol. 134 : 211-242. 25. MYERS, R. E. 1962. Striate cortex connections in the monkey. Fed. Proc. 21 : p. 352. 26. NAUTA, W. J. H., and V. M. BUCHER. 1954. Efferent connections of striate cortex in the albino rat. J. Camp. Neural. 100: 257-286. 27. NIIMI, K., S. KAWAMURA, and S. ISHIMARU. 1970. Anatomical organization of cortico-geniculate projections in the cat. Proc. Japan. Acad. 46: 878-$83. 28. NOBACK, C. R., 1972. Comments on the visual pathways, pp. 485-489. In “Corticothalamic Projections and Sensorimotor Activities.” T. Frigijesi, E. Rinvik, and M. D. Yahr [Eds.]. Raven Press, New York. 29. POLYAK, S. 1957. “The Vertebrate Visual System.” University of Chicago Press, Chicago, pp. 434-437. 30. SPATZ, W. B., J. TIGGES, and M. TIGGES. 1970. Subcortical projections, cortical associations, and some interlaminar connections of the striate cortex in the squirrel monkey. J. Camp. New&. 140 : 155-174. 31. SUZUKI, H., and E. KATZ. 1965. Cortically induced presynaptic inhibition in cat’s lateral geniculate body. Tohoku. J. Exp. Med. 86: 277-289. 32. SZENTAGOTHAI, J., J. HAMORI, and T. TOMBAL. 1966. Degeneration and electron microscope analysis of the synaptic glomeruli in the lateral geniculate body. Exp. Brain Res. 2 : 283 : 301. 33. VALVERDE, F. 1961. Conexiones cortico-talamicas y cortico-pretectales. Estudio experimental en la rata albina. An Anat. 10: 345-359. 34. VON BONIN, G., and P. BAILEY. 1947. “The Neocortex of Macaca Mulatta.” University of Illinois Press, Urbana. 35. WONGRILEY, M. T. T. 1972. Changes in the dorsal lateral geniculate nucleus of the squirrel monkey after unilateral ablation of the visual cortex. I. Comzp. Neural. 146 : 519-548.
