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Organization of the Commissural Connections: Anatomy A. BRODAL Anatotnical Institute, University of Oslo, Oslo, Norway

The functional aspects of the well known close cooperation between the labyrinths of the two sides have been studied rather extensively, but our knowledge of the anatomical basis for this collaboration is still far from complete. A priori one may imagine several anatomical possibilities for a cooperation between the two labyrinths within the central nervous system. 1. It might occur by means of primary vestibular afferents which reach the contralateral vestibular nuclei. 2. A cooperation and a convergence of impulses from the two labyrinths may be mediated by coinmissural connections between the vestibular nuclei of the two sides. 3. Primary vestibular fibres may reach nuclei, for example in the reticular formation, which send fibres to the contralateral vestibular nuclei. 4. Second order neurons from the vestibular nuclei may send fibres to other nuclei, for example in the reticular formation, which project onto the contralateral vestibular nuclei. 5 . Impulses from the two labyrinths may converge at more distant stations in the efferent vestibular connections, by secondary (or tertiary) fibres which cross the midline and are distributed bilaterally, for example, in the spinal cord or in the nuclei of the extrinsic ocular muscles. A priori it is conceivable that all these arrangements may be present. In the following I will deal mainly with the commissural connections, but the other possibilities deserve some attention as well, when one is to consider the basis of the functional collaboration between the two labyrinths. There is no convincing evidence that there are primary vestibular afferents which pass to the contralateral vestibular nuclei, at least not in the mammals studied. Several authors who studied the termination of primary vestibular fibres experimentally with the Marchi or with silver impregnation methods either do not mention fibres of this kind or, having looked for them, did not find them (Rasmussen, 1932; Carpenter, 1960b). In spite of careful search we were unable to find degenerating primary vestibular fibres passing to the contralateral vestibular nuclei in our experimental study in the cat with the Nauta and Glees methods (Walberg et al., 1958). The positive findings reported by some students (Leidler, 1914; Ingvar, 1918) are presumably due to concomitant, inadvertent damage to the vestibular nuclei. Following stimulation of the vestibular nerve Shimazu and Precht (1966) found no evidence for impulse transmission via primary fibres to the contralateral vestibular nuclei. References pp. 175-1 76

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The presence of commissural connections between the vestibular nuclei nf the two sides is well documented. In Golgi studies some authors have found axons of cells in the medial vestibular nuclei which cross the midline (Cajal 1909; Lorente de N6, 1933; Hauglie-Hanssen, 1968), but they could not decide whether the fibres reach the contralateral vestibular nuclei. Following lesions involving different parts of the vestibular nuclei some authors have traced degenerating fibres with the Marchi method (Gray, 1926; Ferraro et al., 1940) or with silver impregnation methods (Carpenter, 1960a; McMasters et al., 1966) to the contralateral vestibular nuclei. Comrnissural connections between the two superior nuclei were described by Gray ( I 926) and McMasters et al. (1966). These authors as well as Carpenter (1960a) in addition describe interconnections between the two lateral nuclei. However, in most of these cases the lesion encroached upon the descending nucleus, which was found to have commissural connections. In a series of studies undertaken in our laboratory (for references see Brodal et al., 1962; Brodal, 1972b) it turned out that the connections of the vestibular nuclei are far more specifically arranged than previously assumed. We (Ladpli and Brodal, 1968), therefore, decided to investigate if the same is the case for the commissural connections, by studying the distribution of degenerating fibres with the Nauta method following lesions restricted to individual vestibular nuclei. The lesions were made stereotactically in adult cats. In a n y study of this kind it is a major problem to take into account fibres passing through the damaged part but coming from other regions or other parts of the nuclear complex than the directly damaged nucleus. Only in this way is it possible to reach definite conclusions. Even if the presence of such fibres of passage excludes conclusions concerning certain projections, it has been possible to define in considerable detail some vestibular commissural connections. Fig. l a shows the lesion in one of our cases, restricted to the superior vestibular nucleus. In cases of this type, a fair number of degenerating fibres can be seen to leave the superior nucleus and to course medially, arching slightly in a ventral and rostra1

Fig. I . Photomicrographs of Nauta stained sections from a cat with a stereotactic lesion restricted to the superior vestibular nucleus. a shows the lesion, b shows degenerating fibres from the lesion crossing the midline (to the right). 300 x . From Ladpli and Brodal (1968).

E

In N

Fig. 2. Diagram showing the distribution of degenerating fibres and their terminal sites in a cat with a lesion restricted to the superior vestibular nucleus (cp. Fig. la). In a series of drawings of' horizontal sections through the blain stem the course of degenerating fibres is shown as wavy lines. The sites of ending are indicated by dots. The density of dottings gives an impression of the intensity of degeneration. Note course of commissural fibres and their termination in all foul contralateral main vestibular nuclei (D, L, M, S ) . From Ladpli and Brodal (1968). Some abbreviations: B.c., brachiurn conjunctivum; N.r.t., nucleus reticularis tegmenti pontis; R.gc., nucleus reticularis gigantocellularis; R.p.c. and R.p.o., nucleus reticularis pontis caudalis and oralis.

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B

Fig. 4. To the left a schematic diagram summarizing the commissural connections of the vestibular nuclei in the cat as determined experimentally. A and B represent transverse sections at levelsindicated. Broken lines indicate commissural connections which are either scanty (between the lateial vestibular nuclei), or whose origin has not been definitely established (between medial vestibular nuclei). From Ladpli and Brodal (1968).

fibres are distributed to the ventral and lateral parts of the descending nucleus. In addition there is some degeneration in the ventralmost areas of the three other main nuclei, very few in the superior. Since lesions of the medial vestibular nucleus will interrupt commissural fibres from the descending nucleus, the precise area of termination of commissural fibres from the medial nucleus cannot be determined. It may be concluded only that the commissural fibres from the medial nucleus, which appear to be rather abundant, must terminate within the same regions as do the commissural fibres from the descending nucleus. It is seen from this brief survey that the four main vestibular nuclei dlfser markedly with regard to their commissural connections. Fig. 4 shows the main points. As to the lateral nucleus the anatomical possibilities for an influence on the contralateral vestibular nucleus seem to be very restricted since the lateral nucleus gives off only very few commissural fibres, mainly to the lateral nucleus of the other side (some also to the descending nucleus, not shown in Fig. 4). It appears that authors who advocate ample interconnections between the two lateral nuclei have used lesions which encroached upon the descending nucleus. The two superior and the two descending nuclei on the other hand, are amply interconnected by commissural fibres. The commissural fibres from these nuclei pursue a different course (Fig. 4, drawings A and B), a point of some interest inphysiological studies. Furthermore, these two nuclei are capable of acting on all four contralateral main nuclei (the small contingent from the descending to the contralateral superior nucleus is not shown in the diagram of Fig. 4), but their main action is obviously on their partner on the opposite side. A final point of interest is that while the commissural fibres from the superior nucleus supply the entire contralateral superior nucleus, all other commissural contingents end only in the ventral parts of the contralateral nuclei. It appears thus that among the main vestibular nuclei the superior is particuReferences p p . 175-1 76

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larly well equipped for a collaboration with its partner on the other side. The medial nucleus probably also has rather abundant connections with its counterpart on the other side. No information could be obtained concerning the origin of possible comniissural connections from the small groups of the vestibular complex, but following certain lesions, degeneration was found in the contralateral groups x and f (see Ladpli and Brodal, 1968, for details), In a study of efferent fibres from the vestibular nuclei in the macaque, baboon and chimpanzee, Tarlov (1969) made observations which agree with our findings on the terminations of the commissural fibres in the cat, even if his making use of fairly large lesions prevented detailed conclusions concerning the sites of origin ot'the commissural fibres. Even if the pattern of commissural connections found in our study is rather specific there are certainly further details which have so far not been brought out. Physiological data concerning the commissural relations are in good accord with the anatomical. Midline incisions of the brain stem in the region where the commissural fibres pass, abolish the inhibition of type-I neurons as well as the excitation of type-I1 neurons which can be evoked by stimulation of the contralateral vestibular nerve (Shimazu and Precht, 1966). Most of the cells influenced by stimulation of the contralateral labyrinth have been found in the superior nucleus, especially ventromedially, and in the rostra1 part of the medial nucleus (Shimazu and Precht, 1966; Markham, 1968; Wilson et a/., 1968), that is in regions which receive many commissural fibres (see Figs. 2 and 3). Concerning the origin of the commissural fibres involved, there is positive evidence for those situated in the medial nucleus (Mano, Oshima and Shimazu, 1968), while the other nuclei have apparently not been studied from this point of view. According to physiological observations the synaptic relationships may be different for different kinds of neurons. Since the latency for the contralateral inhibition of kinetic type-I neurons is shorter than for the tonic ones the former appear to be influenced by a more direct commissural pathway than the latter. It may consist of an inhibitory neuron (excited from the ipsilateral labyrinth) and sending its axon to the contralateral nucleus (Kasahara et al., 1968). The longer latencies for the inhibition of contralateral tonic type-1 neurons and the even longer ones for the excitation of type-11 neurons (Shimazu and Precht, 1966; Markham, 1968) suggest that there may be intercalated neurons in these commissural pathways. Different views on possible arrangements of'this kind have been set forth on the basis of physiological observations, mainly on the medial niicleus (see Shiniazu and Precht, 1966; Markham, 1968; Wilson et d.,1968). The available anatomical data do not permit specific conclusions concerning such arrangements. According to Cajal (1909), Lorente de N6 (1933) and Hauglie-Hanssen (1968) true Golgi I1 type cells appear not to be common in the vestibular nuclei. A few have been found only in the medial and descending nuclei. However, cells sending their axons out of the medial nucleus have been found to give off amply branching collaterals distributed in the immediate neighbourhood of the parent cells (Hauglie-Hanssen,] 968). These cells may presumably function as interneurons within their own nucleus in the transmission of impulses from the ipsilateral

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labyrinth to commissural neurons. They may also be imagined to serve as internuncials for impulses arriving in commissural fibres. As to the other anatomical possibilities for mutual interactions between the impulses from the two labyrinths, mentioned in the introduction, our knowledge is incomplete. An action by cells of the reticular formation, receiving primary vestibular fibres and projecting to the vestibular nuclei on the other side, appears to be unlikely, since only very few primary vestibular afferents reach the reticular formation (in the region close to the nuclei). The available Golgi studies give no information as to whether axons of cells in this part of the reticular formation cross the midline and reach the contralateral vestibular nuclei. However, there are anatomical possibilities for another pathway. Cells in those parts of the reticular formation (mainly the nucleus reticularis gigantocellularis and pontis caudalis) which receive fibres from the vestibular nuclei may send axons or collaterals back to these. This necessitates the presence of crossing fibres in one of the two links. A certain part of the vestibuloreticular projections are crossed (see Fig. 5, and Table I in Brodal, 1972a), namely fibres from the descending vestibular nucleus to the nucleus reticularis gigantocellularis and some fibres from the superior and lateral vestibular nucleus to the reticularis pontis caudalis. Reticulovestibular connections able to mediate an influence o n the contralateral vestibular nuclei would therefore have to be uncrossed. Cells with such axonal trajectories have been observed in Golgi preparations, for example by Scheibel and Scheibel (1958), but information concerning their numbers, particular location and the sites of ending of their axons is not available. The uncrossed vestibuloreticular projections (see Fig. 5) would have to act via reticular cells whose axons cross the midline (see for example, Scheibel and

Fig. 5 . A diagram of the main projections from the vestibular nuclei onto the reticular formation as determined experimentally in the cat by Ladpli and Brodal (1968). The projections from the medial vestibular nucleus could not be determined, but their teiminations are within the territory covered by the fibres from the descending nucleus. N. ret. lat. and N. ret. tegm.: Nucleus reticularis lateralis and tegmenti pontis, respectively. R.g.c. : Nucleus reticularis gigantocellularis in the medulla. R.pc. : Nucleus reticularis parvicellularis. R.p.c. and R.p.0.: Nucleus reticularis pontis caudalis and oralis, respectively. References pp. 175-1 76

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Scheibel, 1958; Valverde, 1961). Neuronal circuits of this kind might be involved in the effects exerted by stimulation of one labyrinth on the contralateral vestibular nuclei as indeed appears from the study of Shimazu and Precht (1966). Following midline transections which abolish the inhibitory commissural responses of type-I neurons, these were replaced by excitatory responses on vestibular nerve stimulation strong enough to produce reticular evoked potentials. A convergence of impulses from the two labyrinths finally occurs in the spinal cord as well as in the oculomotor nuclei and the small nuclei in the mesencephalon adjacent to the latter (nucleus of Darkschewitsch and interstitial nucleus of Cajal). Ascending fibres from the vestibular nuclei are distributed bilaterally to the mesencephalic nuclei mentioned (see Tarlov, 1969; 1970). As to the spinal cord, the medial vestibulospinal tract, arising in the medial vestibular nucleus, gives off crossed as well as uncrossed fibres (Nyberg-Hansen, 1964). This tract, however, does not descend much below the cervical cord. A secondary collaboration of vestibular impulses from the two labyrinths may occur by commissural connections in the spinal cord, since commissural cells appear to be especially abundant in lamina VIII of Rexed (1952) which is the main site of termination of the medial vestibulospinal tract. In this way impulses descending in the two uncrossed lateral vestibulospinal tracts may also collaborate, since this tract as well has most of its terminations in laminaVlII(Nyberg-Hansen and M a x i t t i, 1964). While there are thus several routes by which impulses from the two labyrinths may interact within the central nervous system, the most direct collaboration is by means of commissural connections between the vestibular nuclei. It is obvious from the anatomical data that the vestibular nuclei differ considerably with regard to their commissural connections, and the physiological observations indicate that the anatomical basis for the various commissural effects are probably not identical.

SUMMARY

The labyrinths of the two sides may be imagined to cooperate within the central nervous system by means of several anatomical connections. These are not sufficiently known to permit complete correlations with physiological observations. There is no convincing evidence for primary vestibular fibres passing to the contralateral vestibular nuclei. Commissural connections between the vestibular nuclei are well known to exist. In recent experimental anatomical studies (Ladpli and Brodal, 1968) these connections turned out to be more specifically organized than previously known. The main features are shown in the diagram of Fig. 4. The lateral nucleus gives off only few commissural fibres, mainly to the contralateral lateral nucleus. The superior and descending nuclei are amply interconnected with their partners on the opposite side, but in addition send some commissural fibres to all the other main nuclei. The distribution of the commissural fibres from the medial nucleus could not be precisely defined, except for the fact that they are distributed within the sites of termination of the commissural fibres

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from the descending nucleus. All commissural connections terminate mainly in the ventral parts of the contralateral nuclei, except those which interconnect the two superior nuclei. There is no clear evidence that impulses entering in the few primary vestibular fibres which have been traced to the reticular formation can be transmitted to the vestibular nuclei. Many efferent fibres from the vestibular nuclei terminate in fairly well circumscribed regions of the reticular formation, contralaterally and ipsilaterally. Cells in these regions give off axons or collaterals to the vestibular nuclei, but the detailed course and distribution of these connections are not known in detail. A collaboration between the two labyrinths may finally occur in more peripheral regions (spinal cord and oculomotor nuclei), since fibres from certain of the vestibular nuclei of the two sides meet here. With regard to the spinal cord a collaboration may further be mediated by commissural cells, especially abundant in Rexed’s lamina VlII, which receives most of the vestibulospinal fibres.

REFERENCES

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MCMASTERS, R. E., WEISSA. H. A N D CARPENTER M. B. (1966) Vestibular projections to the nuclei of the exti aocular muscles. Degeneration resulting from discrete partial lesions of the vestibular nuclei in the monkey. Amer. J . Anat., 118, 163-194. MANO,N., OSHIMA, T. AND SHIMAZU, H. (1968) Inhibitory commissural fibers interconnecting the bilateral vestibular nuclei. Bruin Res., 8, 378-382. MARKHAM, C. H. (1968) Midbrain and contralateral labyrinth influences on brain stem vestibular neurons in the cat. Bruin Res., 9, 312-333. NYRERG-HANSEN, R. (1964) Origin and termination of fibers from the vestibular nuclei descending in the medial longitudinal fasciculus. An experimental study with silver impregnation methods in the cat. J. comp. Neurol., 122, 355-367. NYBERG-HANSEN, R. AND MASCI~TI, T. A. (1964) Sites and mode of termination of fibers of the vestibulospinal tract in the cat. An experimental study with silver impregnation methods. J. comp. Neurol., 122, 369-387. RASMUSSEN, A. T. (1932) Secondary vestibular tiacts in the cat. J. comp. Netrrol., 54, 143-171. REXED,B. (1952) The cytoarchitectonic organization of the spinal cord in the cat. J. comp. Neurol., 96, 415-496. SCHEIBEL, M. F. A N D SCHEIBEL, A. B. (1958) Structural substrates for integrative patterns in the brain stem reticular core. In H. H. JASPER,t.D. PROCTOR,R. S. KNIGHTON, W. C. NOSHAY AND R. T. COSTELLO (Eds.), Reticular Forination of /he Brain. Henry Ford Hospital Symposium, Little, Brown and Co., Boston, Mass., pp. 31-55. SHIMAZU, H. AND PRECHT.W. (1966) Inhibition of central vestibular neurons from the contralateral labyrinth and its mediating pathway. J. Neurophysiol., 29, 467-492. TARLOV, E. (1969) The rostra1 projections of the ptimate vestibular nuclei. An experimental study in macaque, baboon and chimpanzee. J . comp. Neurol., 135, 27-56. TARLOV, E. (I 970) Organization of vestibulo-oculomotor projectionsin thecat. Bruin Res., 20,159-179. VALVERDE, F. (1961) Reticular formation of the pons and medulla oblongata. A Golgi study. J. comp. Neurol., 116, 71-100. WALBERG, F., BOWSHER, D. AND BRODAL,A. (1958) The termination of piimary vestibular fibers in the vestibular nuclei in the cat. An experimental study with silver methods. J . conzp. Neurol., 110, 391-119. WILSON,V. J., WYLIE,R. M. AND M A R ~ OL., A. (1968) Synaptic inputs to cells in the medial vestibular nucleus. J. Neurophysiol., 31, 176-185.