An anterior component of the accessory optic system of the cat, with evidence for the absence of reticuloretinal fibers

EXPERIMENTAL

NEUROLOGY

37, 37-49

(1972)

.

An Anterior

Component

of the Accessory

the Cat, with Evidence Reticuloretinal

Rcccivcd

Optic

for the Absence

System

of

of

Fibers

dftr~t IS, lpi-3

A hitherto unreported component of the accessory optic system of the cat brain is described using the de Olmos-Ingram cupric silver method 1-3 weeks after unilateral intraorbital optic nerve section. This component crosses the optic chiasm and leaves the contralateral optic tract to pierce the lateral one-fifth of the cerebral peduncle and the reticular complex of the thalamus at the level where the cerebral peduncle joins the internal capsule. It then swings medially and caudoventrally along the junction between the cerebral peduncle and the substantia nigra. Most of its fibers enter the accessory optic tract (-40T) and its medial andlateral terminal nuclei as they are designated by Hayhow. A few fibers deviate from this path, coursing ventrally and slightly caudomedially through the cerebral peduncle to join the AOT along the route. The failure of this new fiber component to undergo Wallerian degeneration subsequent to the production of peduncular lesions coupled with other evidences indicates its centripetal rather than centrifugal (with respect to the brain) nature. The proposal of centrifugal (efferent) optic fibers originating from the mesencephalic reticular formation (reticuloretinal fibers) cannot be confirmed. Introduction

Recently we described what was interpreted as a centrifugal (or efferent with respect to the brain) optic pathway to the retina in new-born kittens 3-9 days after unilateral eye enucleation (20 ), The brain sections were stained with the Nauta method. Such degenerated fibers were helieved to come from the brain stem reticular formation. and to join the main optic tract after travelling along the cerebral peduncle and the internal capsule. Such a pathway could also be seenin many adult cats similarly treated but with much longer survivals (6 months). Our result was in a sense confirmed by Noback and Mettler (29) who iound persisting normal axons along the route in similarly prepared monkeys long after enucleation. 1 Supported by NINDS

Grants NSO52-10 and NSO8166. 37

Copyright All rights

0 1972 by Academic Press. of reproduction in an>- form

I:Ic. I-rserrc~l

38

LIN

AND

INGRAM

Subsequent to our preliminary report, lesions have been produced along the path of the presumed reticuloretinal fibers to determine if efferent Wallerian degeneration could be provoked. The results were consistently negative. The pattern of degeneration was also studied by the use of the newly developed de Olmos-Ingram method (22) in adult cats after optic nerve transection, with relatively short survivals. In the present commut~ications we describe this afferent (centripetal) pathway more fully and reasons for its afference will be discussed. Materials

and

Methods

In 42 cats intraorbital optic nerve section or ocular enucleation was performed, with postoperative survivals ranging from 2 days to 15 months. These were the same cats used in a previous communication (22) which describes operative and staining procedures. In another seven cats, one or two lesions were placed in that part of the cerebral peduncle which may have been the route of passage of hypothetical centrifugal optic fibers. Postoperative survivals were IO-14 days. Electrodes were inserted vertically. All operations were unilateral and were on the left side. Brains were cut in parasagittal. frontal, and horizontal planes and processed with the Nauta, the Fink-Heimer (Procedure I) and the de Olmos-Ingram methods. References and details have been given before (22). Nissl preparations were routinely available for each cat. Terminologies are based on the atlas of Berman (3 ) Results

The following descriptions of the new accessory optic system (AOS) component under consideration are based on de Olmos-Ingram preparations from one typical cat for each plane of sectioning and are on the side contralateral (right) to the cut optic nerve : Sagittal Plane (Figs. 1-3. Cat 76. 9-day survival). In lateral sections, profuse axonal degeneration could be seen to pass from the optic tract (OT ) onto the junction between the internal capsule (IC) and the cerebral peduncle (CP) . It traveled through the reticular complex of the thalamus (RC) and then along the dorsal edge of the cerebral peduncle to blend indistinguishably with the accessory optic tract (AOT, ref. 16). The direction of passage was clear, judging by the aggregated degenerated fibers and the closely associated “normal axons” (to be discussed later). In the more medial sections, such degeneration was seen to occupy the posteromedial portion of the optic tract (“PM” of Hayhow) and to run rostrocaudally in the substantia nigra (SN) just dorsal to the cerebral peduncle. Here numerous degenerated fibers were also found in the cerebral peduncle intermingling with the adjacent AOT. Farther metliall!;. the de-

ACCESSORY

OPTIC

SYSTEM

39

BIC

FIG. 1. Projection diagram of a portion of the contralateral (right) hemisphere of Cat 76, 9 days after unilateral section of the left optic nerve and prepared with the de Olmos-Ingram method. Parasagittal section. Letters A through D are from lateral to medial. Arrows indicate the new anterior component of the accessory optic system. See test for detail.

could be followed to the lateral terminal nucleus (LTN) of the AOT. Frontal Plane (Fig. 4. Cat 79. lo-day survival). At the mamillary body level, degenerated fibers first appeared at the junction of the internal capsule (IC) and the cerebral peduncle (CP) . Just caudally, degeneration was seen in the lateral one-fifth of the cerebral peduncle and in the reticular complex (RC). More caudally, degenerated fibers were found in an area between the substantia nigra (SN) and the cerebral peduncle, passing mediocaudally and slightly ventrally to merge with the medial terminal nucleus (MTN ) of the .40T. Degenerated fibers were also often seento be dispersed in the cerebral peduncle, fibers which seemedto join the AOT in more caudal sections, including its medial (MTN) and lateral (LTN) tergeneration

minal

nuclei.

Horizontal Plane (Fig. 5. Cat 80. g-day survival). In the more dorsal sections. the degeneration could be seen in the rostrolateral aspect of the cerebral peduncle (CP) and in the reticular comples (RC). These fibers were followed to the AOT and the lateral part of the substantia nigra (SN j. 2k more ventral levels, the degeneration was traced back to the posteromedial portion (PM) of the optic tract and some gathered in the

40

LIN

AND

INGRAM

lateral terminal nucleus (LTN ) of the AOT. In these sections, degenerated fibers passed along the transitional zone between the cerebral peduncle and the substantia nigra toward the medial terminal nucleus (MTN) of the AOT where they intermingled. Degeneration in the cerebral peduncle proper was only occasionally identified, presumably because most of the new AOS component fibers present there were cut across and inconspicuous (4). To recapitulate, we believe that this presumably newly found component of the AOS in the cat leaves the contralateral optic tract, especially its posteromedial portion, at the level where the cerebral peduncle becomes internal capsule. It penetrates the lateral portion of the cerebral peduncle, the reticular complex of the thalamus, and swings medially and caudoventrally along the transitional zone between the cerebral peduncle and the substantia nigra. Finally, it joins the AOT and its medial and lateral terminal nuclei as designated by Hayhow (16). Some fibers deviate from this path, cruising ventrally and slightly caudomedially to meet the AOT along the route. The new AOS component illustrated could be verified, in its entirety, in sections from all of our ten cats with 9-21 days of survival prepared with the de Olmos-Ingram method. Parts of the path could be

FIG. 2. Photomicrograph preparation. X 20.

of Cat

76 brain

as depicted

in Fig.

1A. De Olmos-Ingram

ACCESSORY

OPTIC

41

SYSTEM

seen in 7-clay material (two cats) while it was absent in another three cats with d-day survival or less. Nowhere were we able to detect any preterminal or terminal degeneration along the path except in the known tertniml nuclei of the .AOT. nor did we see tlustlike g-ranular deposits which might indicate retrograde changes ( 27. 3 1 J nnterial, the new On the ilxdateral (,left ) side of the de Olnlus-Ingram

FIG. 3. Higher magnification and “normal” fibers. See text

of the area

framed

for discussion. X80.

in Fig.

2. Notice

the

degenerated

42

LIK

AND

INGRAM

AOS component was either totally invisible or only sporadically and partially seen along the path. Our impression is that such a homolateral pathway could be comparable in course to that of the contralateral side, however. Since the evidence is only suggestive, this pathway will be dropped from further discussion with a passing note that a homolateral AOS was also hinted by others (9, 10, 17, 24 1. The new AOS component was readily verified on the contralateral hemisphere in Fink-Heimer preparations, although never so clearly seen as in de Olmos-Ingram preparations. As for the Nauta method, degenerated fibers along the new component could at best be identified in some animals after exhaustive search. This was also true for a number of other cats with comparable or much longer survivals and prepared with the Nauta technique alone. In another seven cats, one or two large stereotaxic electrolytic lesions intended to intercept the new AOS component were placed in the cerebral peduncle. In spite of relatively long survivals (lo-14 days), which were thought to be essential for the Wallerian degeneration of mammalian optic

FIG. 4. Projection diagram of the contralateral (right) hemisphere of Cat 79, 10 days after unilateral section of the left optic nerve and prepared with the de OlmosIngram method. Frontal section. Letters A through D are from rostra1 to caudal. Arrows indicate the new anterior component of the accessory optic system. See text for detail.

ACCESSORY

OPTIC

SYSTEM

43

efferents, assuming that the latter existed (22 j. only negligible degeneration or none at all could he found in the optic nerves or optic chiasm proper. Degeneration was seen, however, in the dorsocaudal parts of the optic chiasm or tracts and the adjacent hypothalanms, which most probably \vas derived from the fibers of the suixaoptic commissures. This was also true for cats used in other studies (Lin and Ingram, unpublished) in which lesions or needle tracks encroached upon the new AOS component. Discussion

\\‘e recently studied fiber degeneration after optic nerve section in the cat and kitten, and described what was at first thought to be a centrifugal (effereut ) optic pathway coming from the brain stem reticular formation (20). Our interpretation was based upon the fact that this pathway was observed to degenerate in kittens with short survivals and in adult cats only after mucl~ longer degeneration times. Thus it was presunled that these degenerated fillers \vere the result of retrograde rather than \Vallerian degeneration because it is well-recognized that retrograde degeneration in young animals starts soon after nsonal severance while this degeneration generally takes a mucl~ longer time in adult animals (~22 ). There

FIG. 5. Projection diagram of the contralateral (right) hemisphere of Cat 80, 9 days after unilateral section of the left optic nerve and prepared with the de Olmos-Ingram method. Horizontal section. Letters A through D are from dorsal to ventral. Arrows indicate the new anterior component of the accessory optic system. See text for detail.

44

LIN

AND

INGRAM

have been doubts, however, in view of our failure to see Nissl reaction of degeneration in the presumed origins of such a centrifugal pathway in cat or kitten brains, and in view of the lack of characteristic retrograde cellular changes in Nauta preparations of kitten brains ( 15). Cammermeyer (6), in his meticulous study, has said that “dark neurons” are artifacts while others regard them as being physiological or as a reaction to asonal trauma. We saw many “dark neurons” aggregated or scattered throughout Nauta sections of cat and kitten brains, without apparent causal relationship to the operation. Thus, the centripetal (afferent) nature of this pathway should be envisaged. Furthermore, lesions in the cerebral peduncles of seven cats failed to produce Wallerian degeneration in the primary optic pathways. Hence we now believe that the pathway in question is centripetal rather centrifugal. The new AOS component is best revealed in cat brains prepared with the de Olmos-Ingram method, 9 days or longer after optic nerve section. Parts of the pathway could also be seen in the 7-day material. Thus the survivals fall within the optimal times of 7-10 days described for Wallerian degeneration of cat CNS fibers. (22). We emphasize, as others do, that the best survival duration varies not only with animal species, age and individual animals, but also with the fiber systems or fiber groups under study. Thus, although the survival suited for most of the optic afferents and that of the new AOS component may differ somewhat, it should not be too surprising. It has been said that the retrograde axonal degeneration time of adult cat CNS fibers might be as short as 7-10 days after fibers are transected (2, 7, 27, 31). H owever, in many of these studies no serious attempt was made to exclude the possibility of Wallerian or traumatic degeneration, or both, judging by the apparently crude lesions involving intricate fiber systems. Even if such early retrograde axonal degeneration can be established, it should constitute an exceptional rather than a general rule. We were not able to observe granular (dustlike) deposits along the course of the new AOS component to indicate retrograde changes (27, 31). On the other hand, there have been suggestions that the Wallerian degeneration of the cat optic efferents, assuming they exist, may be demonstrable in silver preparations in only 10 days (22), without paying due attention to the possibility that retrograde degeneration of optic afferents might take place at the same time (2. 7, and Lin and Ingram, unpublished). Thus, definite decision on the fiber polarity resides in the comparison of results after lesions made at either end. The present study has shown degeneration in the new AOS component as early as 7 days after optic nerve severance, while absent as late as 14 days after cerebral peduncle lesions. We must, therefore, assume this pathway to be centripetal, since’ there is no prece-

ACCESSORY

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45

dent in the literature for retrograde axonal degeneration 7 days after axotomy while the Wallerian degeneration of the same fibers is either totally absent or appears only long after they are transected. To our knowledge, this new component of the AOS has not been described previously. It is now agreed that there is only one AOS pathway in the cat, which was first described in Nauta preparations by Hayhow ( 16 ). Our new component seems to correspond topographically to the anterior (or inferior) fascicle of the AOS or the anterior (or inferior) AOT of rodents. However, the courses and terminations are different. Detailed comparison cannot be given here due to limited space, and readers are referred to other studies for background information ( 1, 10-12, 16. 17). Hedreen (15) may have seen part of this component in the cat after eye enucleation. The entire new AOS component was not seen perhaps because of the lesser sensitivity of his methods. There have been reports that the AOS may terminate in the subthalamus or mesencephalic reticular formation in various mammalian species after taking courses similar to that of the new component (1, 10, 16, 17). These have been rejected in the recent literature by those who used current silver-impregnation methods. Amunz and Lyubimov (quoted in ref. 21) reported optic termination in the reticular formation after open manual optic tract section, a procedure which probably produces artifacts (21). Schapiro and Holbrook (32) described a totally different AOT in the clog in that it descended into the mesencephalic reticular formation after crossing the posterior commissure. No hint is available in our 42 cats to support this proposal. The initial portion of the present AOS component seems to coincide in location with some of the supraoptic commissural fibers said to be present in sundry forms long after unilateral or bilateral eye enucleation (e.g., 28, 33 j. This could be verified with modern silver techniques in cats subjected to contralateral optic tract lesions (Lin and Ingram, unpublished). Noback and Mettler (29) believed that in enucleated monkeys normal fibers passing into the optic tract from the reticular formation and cerebral peduncle were optic efferents. These might be fibers of the supraoptic commissures, particularly since the observations were not supported by current degeneration methods (18). The concept of the new AOS component was based mainly on use of the recently developed de Ohnos-Ingram method. Because this has not yet received general acceptance, we shall describe some of its characteristics as they are seen in cats after transection of an optic nerve. The chief advantage of this method lies in its near total suppression of normal fibers together with an intensive impregnation of degenerated fibers (Figs. 2, 3). The normal fibers which are present are usually faintly stained and easily

46

LIN

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INGRAM

distinguished from darkly impregnated “normals” such as those of the optic pathways. In the primary optic pathways, in addition to the characteristic degeneration similar to that of the Nauta and Fink-Heimer methods, there are numerous “normal,” somewhat hypcrtrophic, and darkly stained fibers without overt signs of breakdown. Since similar fibers are rarely seen in the contralateral optic nerve or in other portions of the brain. and their appearance coincides with the familiar axonal degeneration, their presence can be indicative of reaction to axonal trauma. Whether such reaction is retrograde or Wallerian is not entirely certain (Lin and Ingram, unpublished). Nevertheless, the efferent polarity of the pathway here described was disproved by the failure to provoke Wallerian degeneration in cats with lesions in the cerebral peduncle. The Fink-Heimer method also shows such “normals” with intensive argyrophilia. However, because of generally present black normal fibers in the background, it is less suited for tracing a minute pathway such as the caudal part of the new AOS component which hence remained undiscovered until now. Returning to the controversial problem of the presumed centrifugal optic fibers, some of the more recent references have been given (22). Here attention is directed only to those studies done in conjunction with the brain stem reticular formation and the AOS. Granit’s (14) observation of retinal activity changes after stimulating the reticular formation has been regarded by many as strong evidence for the existence of centrifugal optic fibers. As was pointed out by others (8, 25), however, such changes could be the result of retinal vascular alterations by way of autonomic fibers (22). The effect of circulation on the ERG is well known (5, 22). Relevant discussion can be found in a previous report (22 j. Hernanclez-Peon et al. (19, 30) and others (26) found centrifugal control of retinal activity in attention to nonvisual sensory modalities or in responding to direct electrical stimulation of the reticular formation. There is no universal agreement, however, the influence of sound on the ERG was not found to be statistically significant (23)) for instance. Furthermore, the criticism of Granit’s study should not be ignored. Palestini, Davidovich, and Hernandez-Peon (30) admitted that “the place of origin of the inhibitory influence remains unsettled and it can only be decided by future lesion experiments.” Cragg (8) thought centrifugal optic fibers existed but failed to find reticuloretinal fibers after brain stem lesions. The present report, with large cerebral peduncle lesions and electrode tracks involving large parts of the reticular formation, also fails to offer confirmation. Hayhow (16, 17) saw some persisting normal fibers in the contralateral AOT after unilateral enucleation and suggested that such fibers could be centrifugal optic (16). This should perhaps not be taken too seriously in view of the possibility of intermingling of the AOT with adjacent nonoptic

ACCESSORY

OPTIC

TABLE ;\BBREVIATIOSS

47

SYSTEM

1 IN

THE

FIGURES

AOT-accessory optic tract BIC-brachium of the inferior colliculus CP-cerebral peduncle DTN-dorsal terminal nucleus of the AOT IC--internal capsule LTN-lateral terminal nucleus of the PIOT MGB-medial geniculate body MTN-medial terminal nucleus of the AOT OT-optic tract PH--posterior hypothalamus PM-posteromedial portion of the OT RC-reticular complex of the thalamus SN-substantia nigra Arrows denote the new anterior component of the accessory optic system. Dots indicate axonal degeneration except in the known terminal nuclei (DTN, LTK, SITN) of the AOT where terminal degeneration is also found.

fibers. Giolli and associates (11-13) indeed found this tract to contain esogenous fibers of nonoptic origin. Marg, Hamasaki, and Giolli (24) believed that the .\OS is electrophysiologically “polarized,” namely, without fibers going to the retina. The present report also fails to establish such an efferent optic pathway involving the izOS. In conclusion, we believe that the occurrence of a new contralateral component of the AOS in the cat, tentatively designated as the anterior (or inferior) fascicle of the AOS. or as the anterior (or inferior) ,\OT, can be established. Centrifugal optic fibers, should they exist at all. do not appear to originate from the brain stem reticular formation. References 1. BAN, T., T. OKI, and K. ZYO. system in the rabbit. Okujimas 2.

BERESFORD,

Bvaift 3.

Rrs.

Stereotaxic 4. BOMXHER, Marchi &Ziib

W. A. 196.5. A discussion 14 : 33-56.

A.L.

BERMAN,

1968. “The Coordinates.”

CAMMERMEYPR.

Ergebtl.

Brain The

on retrograde

changes

in nerve

fibers.

Stem of the Cat. ,4 Cytoarchitectonic .\tlas University of Wisconsin Press, Madison.

D., .L\. BRODAL, and F. method and some silver 83: 150-160.

5. BROWN, K. T. 1968. The 1 Tisiott Krs. 8 : 633-678. 6.

1965. An experimental study on the accessory Folin Atl~mt. Jap. 40 : 62.5615.

WALBERG.

impregnation

electroretinogram:

J. 1962. An evaluation A411nf. Exfw. Gcsck. 36 : l-61.

1960. The relative techniques. i\ Its

of the

components

significance

and of the

values critical their “dark”

optic I’Yo~Y. with of the survey. origins. neuron.

LIN

48

AND INGRAM

7. COLE, M. 1968. Retrograde degeneration of axon and soma in the nervous pp. 269-300. In “Structure and Function of Nervous Tissue.” G. H. [Ed.]. Academic Press, New York. 8. CRACG, B. G. 1962. Centrifugal fibers to the retina and olfactory bulb, composition of the supraoptic commissures in the rabbit. Exfi. Neural.

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CUMMINGS, J. F., and A. DE LAHUNTA. 1469. An experimental study of the retinal projections in the horse and sheep. Ann. N.Y. Ad. Sci. 167: 293-318. 10. GILLILAN, L. A. 1941. The connections of the basal optic root (posterior accessory optic tract) and its nucleus in various mammals. J. Camp. Neural. 74: 9.

307-408. GIOLLI, R.

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14.

328. GRANIT, R. 1955. .I. Neurophysiol. GRANT, G. 1968.

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and antidromic

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16: 38%411.

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accessory optic tract to photic stimulation of the retina and electrical stimulation of the optic nerve in rabbit. Proc. XXI Z+tt. Co,rgr. Plzysiol. Sri. p. 176, Buenos Aires. 25. MEIKLE. T. H., JR., and J. M. SPRAGUE. 1964. The neural organization of the visual pathways in the cat. Int. Rev. Nezlrobiol. 6 : 149-189. 26. MELZACK, R., K. W. KONRAD, and B. DUBROVSKY. 1969. Prolonged changes in central nervous system activity produced by somatic and reticular stimulation. Esp.

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SYSTEhl

49

V. M., and R. W. GUILLERY. 1968. Degeneration in the dorsal lateral geniculate nucleus of the rat following interruption of the retinal or cortical connections. J. Camp. Newel. 134 : 211-242. NICHTERLEIN, 0. E., and F. GOLDBY. 1944. .4n experimental study of optic connections in the sheep. J. Lrluat. 76 : 5947. NOBACK, C. R., and F. A. METTLER. 1970. Commissural and optic efferent fibers in the optic tract, chiasma and nerve of the monkey. ilnnt. Rec. 166: 355. PALESTINI, M., A. DAVIDOVICH, and R. HERNANDEZ-PEON. 1959. Functional significance of centrifugal influences upon the retina. dcta Newel. Latirmm. 5 : 113-131. POWELL, T. P. S., and W. M. COWAN. 1964. A note on retrograde fiber degeneration. J. Anat. 96 : 579-585. SCHAPIRO, H., and J. R. HOLBROOK. 1970. Visual pathways that modify visceral activity. Anat. Rec. 166 : 372. TSANG, Y.-C. 1940. Supra- and post-optic commissures in the brain of the rat. J. comb. Nezrrol. 72 : 535-567. MONTERO,