on the efferent fibers of the cerebellar nuclei in the cat

ON THE EFFERENT FIBERS O F THE CEREBELLAR NUCLEI I N

THE CAT

JAN JANSEN AND JAN JANSEN, JR. Anatomical Institute, University of Oslo, Novway

SEVEN FIGURES

INTRODUCTION

Referring the reader to Jacob ( '28) and Qerebtzoff ( '36 and '41) who give excellent reviews of the literature dealing with our subject, we may confine ourselves here to a brief state- ment of the questions we would like to consider in the present communication.

Recent electrophysiological investigations (e.g. Stella, '44 ; Moruzzi, '47, '50 ; Hampson, '49 ; Snider, NcCulloch and Magoun, '49 ; Magoun, '50 ; Whiteside and Snider, '53) have lent renewed interest to the efferent connections of the cerebellum and raised again the question of the origin of the cerebellofugal fibers in the superior and inferior cerebellar peduncles. Do all subdivisions of the cerebellar nuclei contribute fibers to the brachium conjunctivum as held by Wink- ler ('27) or is the contribution from the central nuclei restricted to the intermediate and lateral subdivisions as maintained by other investigators (e.g. Allen, '24 and Gerebt- zoff, '41) ? Furthermore, do the intermediate and lateral nuclei discharge fibers into the inferior cerebellar peduncle? Is there any appreciable difference in the projection of the fibers from these two nuclei? Do for instance the fibers from the intermediate nucleus go beyond the red nucleus and reach the thalamus as the fibers of the lateral nucleus do? It is a well known fact that many fibers from the cerebellar nuclei

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decussate. What is the actual proportion of crossed to un- crossed connections, and is there any characteristic distribution of the cells of origin of these two Components? Finally the remarkable investigation of Carrea, Reissig and Mettler ( '47) bring to the foreground the exceedingly interesting question whether the cerebellar nuclei send fibers or collaterals to the cerebellar cortex.

These are the principal questions that we have endeavored to elucidate in an extensive series of experiments by means of the method of retrograde degeneration.

MATERIAL AND METHODS

Our experiments were performed on kittens 11 days to a few weeks old (body weight 130 to 500 gm), employing Rro- dal's modification of the Gudden method (Rrodal, '40). Under nembutal anesthesia and aseptic precautions a variety of transections were made of the efferent fibers from the cerebellar nuclei. The animals were kept alive for three to 6 days, varying with the site of the lesion and the age of the animal. The animals were killed by an overdose of nembutal or chloroform and exsanguination whereupon the brains were removed immediately and fixed by submerging in 96% alcohol. The paraffin-imbedded material was cut serially at 15 p, every 4th or 5th section being mounted. For our purpose a postoperative survival of 4 days appeared optimal. At this stage the retrograde changes were as a rule well developed and, as far as could be made out, few of the nerve cells had disin- t egrat ed completely.

The experiments that are referred to in some detail below are selected from a series of more than 100.

In presenting the results we will make use of a diagram comprising a series of frontal sections through the cerebellar nuclei. The diagram is based on drawings made in a projection apparatus of selected sections from a frontal series through the cerebellum of a kitten weighing .500 gm. The 7 levels reproduced in the diagram are marked by numbers (4, 12, 20, etc.) indicating the number of the section of the

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series, number 1 being the section that cuts the rostra1 pole of the nuclear mass. Since the series was cut at 1 5 ~ and every 4th section mounted, the distance between the levels is approximately .5 mm except between levels 28 and 32 where the interval is reduced to one-half.

On the right side of the diagram in figure 1 we have tried to give, as accurately as possible, a picture of the relative size of the nerve cells and of their distribution and relative den- sity within the cerebellar nuclei. In the left half of the diagram are indicated the nuclear boundaries used in this paper. In the other diagrams (figs. 3 to 7) crosses symbolize normal cells and the dots cells showing retrograde changes. The symbols indicate the relative number of normal and pathological nerve cells in the affected cerebellar nuclei. Each symbol represents 5 cells.

It goes without saying that these diagrams in spite of all endeavors merely can give an approximate picture of the changes. We want to point out especially that the count of pathological nerve cells of necessity represents minimum figures. I n the first place it is highly probable that some nerve cells have already disintegrated. Secondly the pale retro- gradely changed cells are rather easily overlooked.

Before referring the experiments it may be appropriate to describe briefly the finer structure of the cerebellar nuclei in kittens, as revealed in Nissl-stained sections. I n that connection we may also deal with the appearance of the retrograde changes of the cells of these nuclei.

The cerebellar nuclei of kit tens

We have adopted Brunner's ('19) terminology for the cerebellar nuclei, distinguishing a medial nucleus (nuc. fastigii), an intermediate nucleus (nuc. interpositus) and a lateral nucleus (nuc. dentatus). Actually the cerebellar nuclei of cats form one mass as pointed out by Brunner (1.c.). The sub- division into three parts is somewhat arbitrary, especially as regards the separation of the intermediate and lateral

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nuclei. I n order to avoid confusion we will give below a description of the cerebellar nuclei in the kitten, hoping that the text and the accompanying diagram will make clear how we have defined and delimited the subdivisions of the central nuclear mass of the cerebellum in the present investigation.

I n kittens, as in the adult cat, one may distinguish a medial, an intermediate and a lateral nucleus, but the boundaries are rather ill-defined in many places.

I n a kitten weighing about 500 gm the nucleus has a rostrocaudal length of about 3 mm. As appears from the diagram (fig. 1) the configuration of the nucleus in frontal sections varies considerably from the rostral pole to the tapering caudal end. The nucleus is composed of large, middle-sized and small cells, just as in adult animals (Snider, '40). All three types of cells are found throughout the nucleus, but the large multipolar cells are located predominantly in the rostral half and in the tail end of the nucleus. The small cells are found especially in the caudal half, here occupying the ventral and medial parts of the nucleus. The cells frequently form smaller groups, too irregular, however, to justify a sub- division of the nucleus fastigii, as suggested by Snider for the adult cat.

Nucleus interpositus. The intermediate nucleus is the largest of the cerebellar nuclei. I n the 500 gm kitten its rostrocaudal axis measures about 2.5mm. The two subdivisions (nuc. interpositus anterior and posterior) described for the adult cat (Snider, '40) are discernible although the border between them is indistinct. I n the nucleus interpositus anterior the middle-sized nerve cells predominate, with small cells scattered in between. The larger nucleus interpositus posterior is preponderantly composed of large and medium- sized cells ; but small nerve cells also occur, particularly along the ventral aspect of the nucleus. Toward the caudal pole the nucleus expands in ventrolateral direction, partly replacing the lateral nucleus which has vanished at this level (fig. 1,

Nucleus fccstigii.

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Fig. 1 A series of sections through the cerebellar nuclei of a kitten. The numbers (4, 12, 20 etc.) refer to the number of the section in the series used for the drawings, number 1 being the section through the rostra1 border of the nuclear complex. On the right side the relative size of the nerve cells and their distribution within the nuclear subdivisions are indicated. The left half shows the boundaries of the nuclei as defined in the present investigation. Nuc. i., nucleus interpositus; nuc. l., nucleus lateralis; nuc. m., nucleus medialis or fastigii.

This diagram is used in figures 3 to 7 t o illustrate the pathological changes observed in the experiments.

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level 40). Rostrally a loosely arranged group of medium-sized and occasionally large cells occupies the space between the nucleus fastigii and the nucleus interpositus (fig. 1, level 2- 20). The group deserves special mention in spite of its modest size, because practically none of the cells have shown changes in our experiments. Toward the caudal border of the nucleus interpositus a string of middle-sized cells establishes a loose connection to the nucleus fastigii.

In horizontal sections the bipartition of the nucleus interpositus stands out quite clearly. The anterior portion seems to have a somewhat denser texture (darker stained) and the medium-sized cells predominate. The posterior portion is lighter and dominated by the large cells. Both portions fuse with the dentate laterally. The posterior portion in addition is loosely connected with the nucleus fastigii as mentioned above.

The description here given of the nucleus interpositus does not conform entirely with the conditions in the adult cat as described by Snider ( '40).

The lateral nucleus in frontal sections appear triangular with rounded corners (fig. 1, 16-36). The rostrocaudal extension of the nucleus is about one-half of the nucleus fastigii (1.5 mm). The large nerve cells dominate the picture, being especially large and crowded in the middle section of the nucleus. The lateral nucleus also contains scattered medium-sized cells, and ventrally as well as in the ventrolateral corner of the nucleus quite a few small, spindle-shaped cells are found, as described by Snider ('40) for the adult cat. Medially the lateral nucleus has extensive contact with the nucleus interpositus.

We are fully aware of the fact that the delimitation given above of the subdivisions of the central cerebellar nuclei are disputable, especially as regards the border hetween the intermediate and lateral nuclei. As defined by Snider ( '40) and Jansen and Brodal ( '40) for the adult cat the lateral nucleus seems to comprise also the adjacent part of the intermediate

Nucleus lateralis.

FIBERS FROM CEREBELLAR NTJCLEI 613

nucleus as delimited in the present investigation. We shall refrain, however, from further discussion of this question for the time being, hoping that text and diagrams will make quite clear to the reader our conception of the nuclear subdivisions in the kitten so that our results can readily be compared with those of other investigators.

T h e retrograde charzges i~ the cells of the cerebellar nuclei

The retrograde reactions observed in the nerve cells of the cerebellar nuclei are essentially similar to those described in the nuclei of the brain stem (Brodal, '39, '40, '41, '43; Brodal and Jansen, '46). We may therefore confine ourselves to a brief description here. Figure 2 illustrates t,ypes of nerve cells found in the cerebellar nuclei of kittens and shows the changes they may undergo when their axone is severed. The classical picture of retrograde reaction with enlarged, rounded cell body, opaque, "milky" cytoplasm, flattened and excen- trically displaced nucleus, is most frequently encountered in the large cells of the fastigial and intermediate nuclei. For some strange reason this typical picture of retrograde reaction is less frequently met with in the lateral nucleus. As a rule the large cells of this nucleus when affected turn pale with finely stippled cytoplasm in the cell body and dendrites which latter become visible in greater length than usual, presumably due to a certain shrinkage of the cell body.

The middle-sized cells of the medial and intermediate nuclei quite frequently display the classical picture of retrograde reaction. Often, however, the homogenized cytoplasm is dif- fusely hyperchromatic instead of pale and opaque. Quite frequently the cells appear shrunken instead of swollen, with fine granules in the cytoplasm (fig. 2).

In the small nerve cells the retrograde changes as a matter of course are less conspicuous, but when fully developed the pale, finely stippled cytoplasm and the dislocated and flattened nucleus will leave no doubt.

Nuc. f

Nuc. i

NUC. 1

Figure 2

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EXPERIMENTAL FINDINGS

Let us start with the question to what extent the fibers from the cerebellar nuclei decussate. The first experiment to be described illustrates the retrograde changes in the cerebellar nuclei after midsagittal section of the cerebellum and tegmen- tum mesencephali with the decussation of the brachium conjunctivum.

Kitten J 27, body weight 200grn, postoperative survival 54 days (fig. 3). Through a small opening in the skull corresponding to the occipital fontanelle the cerebellum and the mesencephalon were split in the midsagittal plane. Upon recovery from the anesthesia the cat displayed a forced rotation around the body axis toward the left for a day. Thereafter a tendency remained for walking and falling toward the left. The microscopic examination of the brain revealed an ideal midsagittal section of the cerebellum, pons and mesencephalon. In this experiment, therefore, the cerebellar commissures and de- cussations as well as the decussation of the brachiurn conjunctivum had been severed in the midsagittal plane.

The distribution of the rethograde changes found in the cerebellar nuclei is illustrated in the diagram (fig. 3 ) . All nuclear subdivisions are affected and apparently a certain pattern is discernible in the distribution of the cellular changes within the different nuclei. In the rostral part of the medial nucleus only a few cells exhibit retrograde degeneration, but the number increases toward the middle of the nucleus (level 28, fig. 3) where the ratio of pathological to normal cells is approximately one to one. I n the caudal half of the nucleus the proportion of pathological to normal cells approximates a three to two ratio.

In the intermediate nucleus pathological nerve cells abound in the rostral half, with only a few normal cells scattered between them. The number of the latter increases, however, in caudal direction and in the caudal third of the nucleus the proportion of pathological to normal cells is reversed. Toward the caudal pole of the nucleus less than 1/10 of the cells display retrograde changes (fig. 3, level 40).

It deserves mention that the nerve cells that form a small group dorsally between the intermediate and medial nuclei appear normal. As a matter of fact, in none of our experiments have we found these cells affected so far.

Fig. 2 Types of normal nerve cells from the cerebellar nuclei (to the left) and cells displaying retrograde reactions (to the right). Nuc. f., nucleus fastigii; nuc. i., nucleus interpositus ; nuc. I., nucleus lateralis. Camera lucida drawing. Leitz oil imm. 1/12. Oc. 5, reduced to X 530.

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Fig. 3 J 27. Midsagittal section of cerebellum, pons and midbrain. Patho- The pathological eells are represented logical changes in the cerebellar nuclei.

by dots, the normal ones by crosses. Each symbol stands for 5 cells.


Most severely affected is the lateral nucleus where pathological nerve cells are found in great numbers throughout. As indicated in the diagram (fig. 3, levels 20, 28, 32), however, many normal cells, roughly estimated one-third of the total number, are scattered between the degenerating cells.

This experiment warrants the conclusion that more than one-half of the fibers from the cerebellar nuclei are crossed, presumably, decussating either within the cerebellum or in the decussation of the brachium conjunctivum. The crossing fibers are derived from all three nuclei. Their cells of origin are found predominantly in the caudal half of the medial nucleus and in the rostral half of the intermediate nucleus, while they are distributed more evenly throughout the lateral nucleus.

These findings raise the question to what extent the crossing of the cerebello-efferent fibers takes place within the cerebellum. Do fibers from all three nuclei decussate in the cerebellum as well as in the midbrain? The following experiment answers this question.

Kitten J 68, body weight 250 gm, posioperative survivd 5 days (fig. 4). Through an opening in the occipital bone the posterior vermis and the roof of the 4th ventricle were exposed. With a Graefe’s knife the cerebellum was split in the midsagittal plane. There were no conspicuous symptoms following the operation. The microscopic examination of the brain revealed a sagittal lesion in the cerebellum slightly displaced to the right of the midplane so that some of the medially situated cells of the right fastigial nucleus may have been affected directly by the lesion.

The diagram (fig. 4) shows the distribution of the nerve cells exhibiting retrograde changes in this experiment. The definitely pathological cells are confined to the fastigial nuclei. I n the intermediate and lateral nuclei not a single cell was observed which exhibited the picture of retrograde reaction.

In the fastigial nucleus the proportion of retrograde to normal cells increases on passing from the rostral to the caudal pole of the nucleus, but apparently less so than in the preceding experiment.

A count of pathological and normal cells in the fastigial nucleus gave for the left nucleus 561 and 1516 cells respectively, for the right nucleus 893 and 1508 cells.

From this experiment we feel justified l o draw the conclusion that at least one-quarter of the fibers from the medial

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Fig. 4 J 68. Midsagittal section of cerebellum. Pathological changes in the cerebellar nuclei. Symbols as in figure 3. Where no symbols, no pathological cells observed.


nucleus decussate in the cerebellum, while none of the fibers from the intermediate and lateral nuclei seem to do so.

The observation that the pathological changes in the caudal half of the nucleus fastigii apparently are less lmassive in this experiment than in the preceding one where the midbrain also was split raises the question whether fibers from the nucleus fastigii pass rostralward and join the brachium conjunctivum. The next experiment gives an answer to this question.

Kitten. J 114, body weight 230 gm, postoperative survival 44 clays (fig. 5). An opening was made in the skull on the right side immediately in front of the tentorium and a part of the right occipital lobe was removed in order to expose the tectum niesencephali. An attempt was then made to cut the right brachiurn conjunctivum in the isthmus region by means of a Graefe’s knife.

On microscopic examination it appears that the brachium conjunctivum dextrum has been almost completely severed, possibly spar- ing the fibers situated most dorsomedially. Adjacent folia of the anterior lobe are superficially injured. I n caudal direction the lesion encroaches slightly on the rostra1 pole of the right intermediate nucleus.

In the cerebellar nuclei nerve cells undergoing retrograde degeneration are found in the ipsilateral intermediate and lateral nuclei and in the contralateral medial nucleus, as indicated in the diagram (fig. 5 ) . As regards the latter nucleus the changes are confined to the caudal half where a little less than 20% of the cells exhibit retrograde changes. A few suspect cells were observed also in the homolateral fastigial nucleus.

I n the homolateral intermediate and lateral nuclei the changes are massive, without, however, affecting all the nerve cells a t any level. The number of normal cells increases in caudal direction, and in the intermediate nucleus the normal cells by fa r out number the degenerating ones toward the caudal pole, as is evident from the diagram (fig. 5 ) .

We conclude from this experiment that about one-fifth of the nerve cells in the caudal half of the medial nucleus send their axones rostralward into the contralateral brachium conjunctivum, and that the great majority of the cells of the intermediate and lateral nuclei send their axones into the ipsilateral brachium conjunctivum.

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Fig. 5 J 114. Transsection of brachium conjunctivum dextrum. Patho- logical changes in the cerebellar nuclei. Symbols as in figure 3. Where no symbols no pathological cells observed.


This experiment brings to the foreground the question where the remaining cells send their axones. The number of intact cells is too great to be explained by possibly incomplete transection of the brachium conjunctivum. The possibility that the fibers from these cells decussate in the cerebellum and join the contralateral restiform body may be ruled out since midsagittal splitting of the cerebellum leaves the intermediate and lateral nuclei intact (fig. 4). Another possible explanation is that the cells in question send their axones into the homolateral restiform body. We will now turn, therefore, to an experiment involving lesion of the restjform body.

Ki t t en J 66, body weight 290grn, postoperative survival 5 days (fig. 6 ) . Upon removal of a part of the occipital bone on the left side the roof of the 4th ventricle was split and from the lumen of the ventricle an attempt was made to cut the left restiform body with a Graefe's knife. After recovery from the anesthesia the animal rested on the left side and had forced movements to the left.

The microscopic examination revealed that the left restiform body had been practically completely severed, possibly leaving some fibers in the extreme lateral par t intact. I n addition a major part, if not all of the left brachium conjunctivum is involved in the lesion but the brachium pontis is spared.

The retrograde changes in the cerebellar nuclei accompanying this lesion are shown diagramatically in figure 6. The changes are confined to the ipsilateral intermediate and lateral nuclei and the medial nucleus on both sides. I n the contralateral intermediate and lateral nuclei not a single cell with typical retrograde changes was observed.

As regards the intensity and the distribution of the pathological changes within the affected nuclei it is remarkable that in spite of the almost complete transection of the brachium conjunctivum and the restiform body on the left side normal nerve cells are found in the nucleus interpositus as well as in the lateral nucleus. As appears from the diagram (fig. 6) the proportion of normal to pathological nerve cells increases toward the caudal end of the nuclei. I n principle the distribution of the pathological changes within the intermediate and lateral nuclei in this experiment has a striking resemblance to the findings in the preceding experiment where the right brachium conjunctivum alone was severed (fig. 5).

The distribution of the retrograde changes within the fastigial nuclei shows a conspicuous difference on the two sides. In the first place the total number of pathological nerve cells observed is greater

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in the nucleus contralateral to the lesion, the ratio of pathological to normal cells being approximately two to one. However, in spite of this predominance of pathological cells contralateral to the lesion, an inverse ratio is found in the rostral half of the nuclei where the pathological nerve cells in the ipsilateral f astigial nucleus outnumber those in the contralateral nucleus approximately 4 to 3. I n the rostral third of the fastigial nucleus there are even three times as many pathological cells ipsilateral to the lesion, while in the caudal third of the nucleus, on the other hand, there are found very few pathological cells in the ipsilateral nucleus. No less remarkable than these changes is the fact that so great a proportion of the cells of the fastigial nuclei remains intact when the restiform body as well as the brachium conjunctivum have been cut.

Although the lesion is not confined to the restiform body in the present experiment we believe that it contributes definitely to the solution of the question under consideration. The experiment in our opinion strongly suggests that the presence of intact nerve cells in the ipsilateral intermediate and lateral nuclei after transection of the brachium conjunctivum cannot be explained by a possible component of efferent fibers from these nuclei in the restiform body. A comparison between figures 5 and 6 makes evident, it seems to us, that the number of fibers passing from the nuclei in question into the restiform body must be small, if such fibers do exist at all.

The experiment under consideration furthermore seems to permit the conclusion that the cells of the fastigial nucleus that send their fibers into the ipsilatcral restiform body are located predominantly in the rostral half of the nucleus, while the decussating fibers forming the hook bundle of Rus- sell are derived primarily from cells in the caudal half of the nucleus.

The experiments referred so far have shown conclusively that all cerebellar nuclei contribute fibers to the brachium conjunctivum. Although the method employed in this investigation does not permit a detailed analysis of the terminal distribution of the fibers of the brachium conjunctivum, the experiment to be described next may shed some light on the interesting question to what extent fibers from all three major


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Fig. 6 Transsection of left restiform body and brachium conjunctivum sinistrum. Pathological changes in the cerebellar nuclei. Symbols as in figure 3. Where no symbols, no pathological cells observed.

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subdivisions of the cerebellar nuclei pass beyond the mesencephalon (nucleus ruber ) .

Kitten J 42, body weight 160gm, postoperative survival 4% dnys (fig. 7) . Through a small opening in the skull immediately to the right of the caudal end of the sutura sagittalis a right hemisection was made of the brain stem by means of a Graefe’s knife. After the operation the animal had forced movements to the right and a tendency t o fall to the same side.

The microscopic examination revealed? in addition to lesions in the right cerebral hemisphere, an almost complete hemisection of the brain stem on the right side at the level of the rostral extremity of the magnocellular part of the red nucleus, i.e. immediately in front of the exit of the oculomotor nerve. Thus in this experiment all fibers of the brachium conjunctivum that pass beyond the level of the red nucleus on the right side must have been cut.

The pathological changes observed in the cerebellar nuclei are confined to the nuclei of the left, i.e. contralateral side. As appears from the diagram (fig. 7 ) the left dentate nucleus is most severely affected. Nerve cells exhibiting retrograde changes are found throughout the rostrocaudal extension of the nucleus, especially in the middle and ventral parts. I n comparison the number of affected nerve cells observed is very small in the left intermediate nucleus. Upon the whole, however, this nucleus looks paler than its right side counter- part, possibly due to a certain disintegration of nerve cells in the nucleus on the left side. Even so it is evident that the nucleus interpositus sinister is considerably less affected in this experiment than the adjacent lateral nucleus.

Conspicuous cellular changes are furthermore found in the caudal third of the left fastigial nucleus where a considerable number of nerve cells show characteristic retrograde reaction (fig. 7 ) . Similar changes were not observed in the nerve cells of the nucleus on the opposite side, i.e. ipsilateral to the lesion.

With a certain reservation due to the fact that the lesion touches tho, rostral pole of the red nucleus this experiment secms to warrant the following conclusions : (1) The fibers of the brachium conjuiictivum that pass rostrad beyond the level of the red nucleus are all crossed. (2 ) The vast majority of these fibers are derived from the lateral nucleus, a modest number originate in the nucleus interpositus, and some come from a group of nerve cells in the caudal third of the fastigial nucleus.

FIBERS FROM CEREBELLAR NUCLEI

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\-*-cJ 3 Fig. 7 J 42. Left hemisection of the brain stem at the level of the rostrd

pole of the red nucleus. Pathological changes in the cerebellar nuclei. Symbols as in figure 3. Where no symbols, no pathological cells observed.

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COMMENT

Our experiments have given a positive answer to the question that was raised in the introduction, vis. whether all cerebellar nuclei contribute fibers to the brachium conjunctivum, thus confirming the view advocated by Winkler ( '27). The component from the fastigial nucleus is evidently the one traced by Rasmussen ('33) in Marchi preparations into the reticular formation of the midbrain. It is interesting to note that the component from the nucleus fastigii takes its origin from cells in the caudal half of the nucleus and that these fibers apparently all decussate in the cerebellum (fig. 5 ) while none of the fibers from the lateral and intermediate nuclei seem to do so. The fact that the fastigial nucleus discharges fibers to the superior as well as to the inferior cerebellar peduncle may possibly prove an anatomical feature of im- portance for the explanation of the observation by Morruzzi ('50) and Nulsen, Black and Drake ('48) that inhibition as well as facilitation of motor activity may be elicited from one and the same point of the cortex of the anterior cerebellar lobe.

As regards the further fate of the fibers of the brachium conjunctivum it becomes obvious on comparing figures 5 and 7 that a majority of the fibers terminate in (or at the level of) the red nucleus, but we have also concluded (with a certain reservation, see p. 624) from the experiment illustrated in figure 7 that all three nuclear subdivisions send fibers rostrally beyond the mesencephalon. Approximately tu-o-thirds of these fibers are derived from the lateral nucleus, while the last third seems to be composed of almost an equal number of fibers from the nucleus interpositus and the fastigial nucleus. The fastigial component originates from cells in the tail end of the nucleus (fig. 7) . Comparison of the experiments illustrated in figures 5 and 7 brings out, furthermore, the interesting point that while approximately one-half of the fibers from the dentate nucleus to the brachiuni conjunctivum pass beyond the red nucleus, little more than 10% of the fibers from the nucleus interpositus do so. This observation gives


an indication of functional difference between the two nuclei in question.

It is well known that some Purkinje cells in the vermis and in the flocculus send their axones through the restiform (juxta restiform) body directly to the vestibular nuclei (for literature see Jansen and Brodal, '40). Our experiments leave no doubt, however, that the vast majority of cerebellofugal fibers passing through the restiform body are derived from the fastigial nuclei. A comparison of the experiments illustrated in figures 4, 5 and 6 leads to the conclusion that approximately one-half of these fibers originate in the contralateral fastigial nucleus, especially the caudal two-thirds of the nucleus. The cells of origin of the direct fibers are more concentrated in the rostra1 third of the nucleus.

As regards the question of discharge of efferent fibers from the lateral and intermediate nuclei to the restiform body, our investigation cannot give a conclusive answer because we have no experiment where the lesion is confined to the restiform body. It seems evident, however, on comparing an experiment where the restiform body and the brachium conjunctivum are cut (fig. 6) with one where the lesion is confined to the brachium conjunctivum (fig. 5) that if at all efferent fibers pass from the lateral and intermediate nuclei to the restiform body their number must be relatively modest.

When we review and compare the experiments referred to above it seems obvious that the sum total of pathological changes following midsagittal section of the cerebellum and brain stem and practically complete transection of the restiform body as well as the brachium conjunctivum does not claim all the nerve cells of the cerebellar nuclei. There still remain, as fa r as we can see, in all subdivisions nerve cells that are left intact. The explanation for the apparent insensibility of these cells to lesions of the kind described above still remains a puzzle. We can merely point out possibilities that must be left for further investigations.

First of all it seems appropriate to consider whether the cerebellar nuclei send efferent fibers by way of the brachium

628 J A N J A N S E N A N D J A N J A N S E N , JR.

pontis that we have not dealt with so far. TJnfortunately we do not have in our material any experiment where the lesion is confined to the brachium pontis, and in those experiments where the brachium pontis is involved in combination with the two other peduncles it is not completely transected. Our material does not permit, therefore, a definite answer to the question. However, in those experiments where the brachium pontis is affected, we have not been able to detect retrograde changes in the nerve cells in areas of the cerebellar nuclei that are left intact when the lesion is restricted to the restiform body and the brachium conjunctivum.

Therefore, although our experiments do not exclude that the cerebellar nuclei discharge fibers through the brachiurn pontis they seem to warrant the tentative conclusion that possible cerebellofugal fibers in the brachium pontis are not likely to be so numerous as to account for all the cells that are left intact in the cerebellar nuclei in our experiments.

Another possible explanation for the intact cells is that they represent intrinsic cerebellar neurons. In their compre- hensive investigations of the climbing fibers Carrea, Reissig and Mettler (’47) arrived at the conclusion that these terminals” are chiefly, if not entirely, endings of fibers originating in the cerebellar nuclei (possibly as recurrent collaterals of the cerebello-fugal fibers emerging from the nuclei or as primary axons from the small nuclear cells).”

Our attempts to find additional support for this conclusion by means of the modified Gudden method have not yielded definite results. I n experiments where the lesions were confined to the cerebellar cortex and the subcortical white matter we have not been able to find in the cerebellar nuclei nerve cells displaying typical retrograde changes. From this failure it by no means follows that nucleocortical connections do not exist. As suggested by Carrea, Reissig and Mettler the nucleocortical fibers may merely represent collaterals of efferent fibers and it is entirely possible that the destruction of the terminals of these collaterals affects the nerve cells so slightly


that the changes are hardly discernible with the method employed.

The fact remains that a considerable number of cells in the cerebellar nuclei cannot be accounted for by our experimental procedure. The time factor may be partly responsible. Pos- sibly the survival period has been too short in our experiments. Bifurcation of the axons or the presence of numerous collaterals may also play a role in this connection preventing the development of retrograde reactions. The question must be left for further investigation. But it seems appropriate to point out that a considerable number of the cells that appear normal in our experiments are large neurons. It is remarkable, furthermore, that in our experiments so many of these large, apparently intact neurons are found in the caudal extremity of the nucleus interpositus. I n the lateral nucleus they are more scattered, while in the fastigial nucleus intact cells appear to be more numerous in the rostral than in the caudal half of the nucleus.

SUMMARY

The present investigation of the efferent fibers of the cerebellar nuclei in the cat by means of the modified Gudden method has led to the following conclusions.

1. All cerebellar nuclei, i.e. the lateral nucleus, nucleus interpositus and the fastigial nucleus, contribute fibers to the brachium conjunctivum.

The bulk of the fibers of the brachiuni conjunctivum are derived from the lateral and intermediate nuclei. These fibers decussate in the midbrain (decussatio brachiorum con- junctivorum), none in the cerebellum.

The fastigial component of the brachium conjunctivum originates from cells in the caudal two-thirds of the nucleus. These fibers decussate in the cerebellum and join the contralateral brachium conjunctivum. 4. With a certain reservation (see p. 624) it is concluded

that approximately one-third of the fibers of the brachium conjunctivum pass rostral beyond the level of the red nucleus.

2.

3.

630 JAN JANSEN AND J A N JANSEN, JR.

Of these fibers about two-thirds are derived from the lateral nucleus while the remaining one-third of the fibers originate with approximately equal parts from the nucleus interpositus and the fastigial nucleus.

This conclusion implies a certain functional distinction between the intermediate and lateral nuclei, the former nucleus being more intimately associated with the midbrain mecha- nisms, while the latter appears more closely tied up with the thalamocortical systems.

The majority of the cerebellofugal fibers from the fastigial nucleus pass to the restiform body. Approximately one- half of these fibers decussate before entering the restiform body.

6. The nucleus interpositus and the lateral nucleus contribute few, if any, fibers to the restiform body.

7. No commissural connections between the intermediate and lateral nuclei on both sides could be ascertained by the method employed in this investigation.

8. After transection of the restiform body and the brachium conjunctivum a considerable number of larger, middle sized and small nerve cells still appear normal in the lateral, intermediate as well as medial nuclei. Intact cells are particularly conspicuous in the caudal extremity of the nucleus interpositus and in the rostra1 half of the fastigial nucleus. Although the insensibility of these cells may he due to various factors (see p. 627) the evidence seems to favor the conclusion that some neurons in the cerebellar nuclei are intrinsic cerebellar elements, a conclusion which would be consistent with the view expressed by Carrea, Reissig and Mettler ('47).

5.

LITERATURE CITED

ALLEN, W. F. 1924 Distribution of the fibers originating from the different basal cerebelIar nuclei. J. Comp. Neur., 36: 399-439.

BRODAL, A. 1939 Experimentelle Untersuchungen uber retrograde Zellver- anderungen in der unteren Olive naeh Gsionen des Kleinhirns. Z. f. d. ges. Neur. Psyehiat., 166: 646-704.

Modification of Gudden method for study of cerebral localiza- tion. Arch. Neur. a. Psychiat., 43: 46-58.

1940

FIBERS FROM CEREBEUAR NUCLEI 631.

BRODAL, A. 1941 Die Verbindungen des Nucleus cuneatus externus mit dem Kleinhirn beim Eaninchen und bei der Katze. Z. f . d. ges. Neur. Psychiat., 171: 167-199.

1943 The cerebellar connections of the nucleus reticularis lateralis (nucleus funiculi lateralis) in rabbit and cat. Experimental investigations. Acts psychiat., Kbh., 18: 171-233.

BRODAL, A., AND J. JANSEN The ponto-cerebellar projection in the rabbit and cat. Experimental investigations. J. Comp. Neur., 84: 31-118.

BRUNNER, H. 1919 Die zentralen Kleinhirnkerne bei den Gugetieren. Arb. Neur. Inst., Wien, 38: 200-277.

CARREA, Rain M. E., MAGDALENE REISSIG AND F. A. METTLER 1947 The climbing fibers of the simian and feline cerebellum. Experimental inquiry into their origin by lesions of the inferior olives and deep cerebellar nuclei. J. Comp. Neur., 87: 321-366.

The anatomy of the primate brachium conjunctivum and associated structures. J. Comp. Neur.,

Le pedoncule cBr4belleux suphrieur e t les terminai- sons r6elles de la voie cBr6bello-thalamique. MBmoires d. L 'Acad. Royale d. MBd. d. Belgique, 35: 1-58.

1941 Les bases anatomiques de la physiologie du cervelet. La Cellule, 49 : 71-166.

HAMPSON, J. L. Relationship between cat cerebral and cerebellar cortices. J. Neurophysiol., 1%: 37-50.

JACOB, A. 1928 Das Kleinhirn. v. Mollendorff 's Randbuch der mikroskopischen Anatmie des Menschen, 4: 674-916, J. Springer, Berlin.

JANSEN, JAN, AND ALP BRODAL Experimental studies on the intrinsic fibers of the cerebellum. 11. The cortico-nuclear projection. J. a m p . Neur., 7.9: 267-321.

MAQOUN, H. W. Caudal and cephalic influences of the brain stem reticular formation. Physiol. Rev., $0: 459-474.

MORUZZI, Q. 1947 Sham rage and localized autonomic responses elicited by cerebellar stimulation in the acute thalamic cat. Oxford, Proc. XVII Int. Physiol. Con., 114-115.

Problems in cerebellar physiology. Charles C Thomas, Spring- field, Illinois, pp. 116.

NULSEN, F. E., 8. P. W. BLACK AND C. G. DRAKE 1948 Inhibition and facilitation of motor activity by the anterior cerebellum. Federation Proc., 7: 86-87.

Origin and course of the fasciculus uncinatus (Russell) in the cat, with observations on other fiber tracts arising from the cerebellar nuclei. J. Comp. Neur., 57 : 165-197.

Morphology of the cerebellar nuclei in the rabbit and cat. J. Comp. Neur., 72: 399-415.

1949 A cerebello-bulbo- reticular pathway for suppression. J. Neurophysiol., 1% : 325-335.

1946

CARREA, R. M. E., AND FRED A. M ~ m m 1955

101: 565-690. GEmTZOm, MICHEL A. 1936

1949

1940

1950

1950

I~~SMUSSEN, A. T. 1933

SNIDER, R. 8.

SNIDER, R. S., W. 8. MNULLOCH AND H. W. MAGOUN

1940

632 J A N JANSEN AND JAN JANSEN, JR.

STELLA, G. 1944 Nuove osservazioni sugli effetti della stimulazione del paleo- cerebello dell ' animale decerebrato. Atti SOC. Med. Chir. Padova, 85: 5-7. Cited from Moruzzi, '50.

WHITESIDE, J., AND R. S. SNIDER Relation of cerebellum to upper brain stem. J. Neurophysiol., 16: 397-413.

WINKLER, C. 1927 Anatomie du syseme nerveux. 3. Le cervelet: 108-367, De Erven F. Bohn, Haarlem.

1953

on the efferent fibers of the cerebellar nuclei in the cat

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