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Differential Course and Organization of Uncrossed and Crossed Long Ascending Spinal Tracts
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Differential Course and Organization of Uncrossed and Crossed Long Ascending Spinal Tracts 0. OSCARSSON Institute of Physiology, University of Lund, Lund (Sweden)
Recent investigations on ascending spinal tracts with electrophysiological technique suggest that uncrossed and crossed tracts differ in two respects (Magni and Oscarsson, 1962; Holmqvist and Oscarsson, 1963): (1) uncrossed tracts are located dorsally of the crossed tracts; (2) uncrossed tracts are polysynaptically activated only from ipsilateral nerves and crossed tracts both from contralateral and ipsilateral nerves. Furthermore, some evidence suggests that the cell bodies of uncrossed and crossed tracts occupy different areas in the grey matter. The identification of uncrossed and crossed tracts has been based on the hlstological finding that, in most spinal cord segments, primary afferents terminate exclusively, or almost exclusively, on the ipsilateral side (Schimert, 1939; Escolar, 1948; Liu, 1956; Sprague, 1958). Hence, tracts activated monosynaptically from ipsilateral afferents are uncrossed and tracts activated monosynaptically from contralateral afferents, crossed at the spinal level. METHODS
The results were obtained on electrical stimulation of nerves or dorsal roots. The activity evoked in ascending tracts was recorded either as a mass discharge led from dissected fascicles of the spinal cord or studied by intra-axonal recording from single fibres. Of these two methods the former warrants a more detailed description. The technique of recording from isolated strands of the cord was devised by Rudin and Eisenman (1951) for the study of properties of fibres in the cord. It was developed further and used extensively for studying the functional organization of various ascending tracts by Laporte et al. (1956), Lundberg and Oscarsson (1961), and Holmqvist and Oscarsson (1963). The fascicles are prepared as follows. The spinal cord is transected and one pair of roots severed caudally of the transection. The dorsal funiculi are stripped off for a distance of about 2 cm in caudal direction. The remaining part of the cord is divided into the midline and the ‘cord-halves’ (except dorsal funiculi) split longitudinally into subdivisions of various sizes, here called ‘fascicles’. The subdividing is done by cutting with a pair of fine scissors. In the cat, four or five fascicles can be made on each side
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without difficulty. The dissected fascicles are mounted on electrodes for monophasic recording of discharges in ascending tracts, one electrode being in contact with the severed end, the other on the dissected part close to its site of separation from the intact cord. The method can be used for determining the exact position of individual tracts with known functional properties: there is remarkably little destruction of ascending fibres during the dissection and the size of the fascicles can be assessed afterwards by histological methods. The main limitation of the method is that potentials due to activity in unmyelinated and thin, myelinated fibres are too small to be detected. The same limitation holds for the other method which has been used: intra-axonal recording from single fibres. Successful impalement occurs very seldom with fibres having a conduction velocity lower than 25-30 mjsec which would correspond to a diameter of 4-5 ,u (assuming that the Hursh factor of 6 is valid in the CNS). RESULTS
Recording from dissected fascicles in mammalian species
The records in Fig. 1 illustrate the differential characteristics of mass discharges evoked in dorsally and ventrally located tracts. Two fascicles were dissected at the upper lumbar level of the spinal cord in a monkey. The transectional areas of the
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Fig. 1. Discharges in ascending spinal tracts evoked by volleys in muscle and skin afferents of ipsilateral and contralateral hindlimb nerves. Monkey. The muscle (hamstring) and skin (lateral sural) nerves were stimulated at a strength of about 20 times threshold. Records E-L were obtained from the dissected fascicles (i) and (ii) as indicated. The upper and lower traces show the discharge recorded simultaneously at two speeds. The ingoing volleys (A-D) were recorded from the dorsal roots 4.2 cm below the cord dissection at mid-L2. The fast time scale applies to A-D and upper traces in E-L. Voltage scale applies to E-L. (From Oscarsson el al., 1963b). References p . 1751176
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fascicles are shown in the diagram. The upper and lower traces in Fig. 1, E-L show the discharges recorded at two speeds and led from the fascicles as indicated. The top traces (A-D) show the ingoing primary afferent volleys recorded triphasically from the dorsal roots about 4 cm more caudally. Tracts ascending in the dorsal fascicle were activated by volleys in muscle (E) and skin (F) afferents of ipsilateral nerves, whereas no trace of activity was evoked from contralateral nerves (G, H). The ventral fascicle contained tracts activated from contralateral as well as ipsilateral nerves. The latency of the initial component of the mass discharges evoked from ipsilateral nerves in the dorsal fascicle (E, F) and from contralateral nerves in the ventral fascicle (K, L) was 1.O-1.4 msec when measured relatively to the ingoing volley. This short latency proves that the transmission was monosynaptic. It can be concluded that the dorsal fascicle contains uncrossed tracts and the ventral fascicle, crossed tracts. On the other hand, there was no evidence for monosynaptic excitation from ipsilateral nerves to tracts in the ventral fascicle. The initial part of the discharges evoked from ipsilateral nerves in this fascicle (I, J) was related to group I1 muscle afferents and low threshold cutaneous afferents. The long latency indicates that the transmission was:poly sy naptic. I PSIL.
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Fig. 2. Discharges recorded at the third cervical segment from tracts activated by stimulation of ipsilateral and contralateral muscle (hamstring) and skin (superficial peroneal) nerves in the hindlimbs. Cat. The records were obtained from fascicles i-iii as indicated. The upper and lower traces show the discharges recorded simultaneously on a fast and slow time base. Middle traces in A-D show ascending volleys recorded from the dissected dorsal funiculi at C3. Time scales in msec. Distance from stimulating electrode on hamstring nerve to C3 about 37 cm. (From Holmqvist and Oscarsson, 1963.)
Similar observations have been made on recording from fascicles dissected in the upper lumbar region of the phalanger, rabbit, cat, dog, and monkey (Magni and Oscarsson, 1962; Holmqvist and Oscarsson, 1963, Oscarsson et al., 1963b). In all these species uncrossed tracts occur in the dorsal half of the lateral funiculus and crossed tracts in the area ventrally thereof. There is little overlap of the areas containing uncrossed and crossed tracts and the boundary between them corresponds approximately to a horizontal line going through the central canal. Recording from fascicles dissected at the cervical level has disclosed that the borderline between uncrossed and crossed tracts varies according to the spinal cord
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level and the segmental origin of the tracts. In the experiment of Fig. 2, made on the cat, three fascicles (i-iii) were dissected at the level of the third cervical segment. Muscle and skin nerves in the hindlimbs were stimulated. The arrangement of the records corresponds to that in the previous figure, except that the middle traces in A-D show the afferent volleys led from the dorsal funiculi dissected for recording at C3. In the dorsal fascicle (i) ipsilateral but not contralateral nerves evoked monoand polysynaptic discharges (A-D). The intermediate and ventral fascicles (ii and iii) contained tracts which received strong excitatory effects from contralateral nerves and weaker effects from ipsilateral nerves. A large monosynaptic discharge was evoked from contralateral group I afferents in the intermediate fascicle (G). Volleys in skin and high threshold muscle afferents in ipsilateral and contralateral nerves evoked a late activity with a latency suggesting polysynaptic excitation (E-L). These observations show that the borderline between uncrossed and crossed ‘hindlimb tracts’ has shifted dorsally at the cervical level when compared with the lumbar level (Holmqvist and Oscarsson, 1963). IPSIL.. MUSCLE
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-Eclrr Fig. 3. Discharges recorded at the third cervical segment from tracts activated by stimulation of ipsilateral and contralateral muscle (deep radial) and skin (superficial radial) nerves in the forelimbs. Cat. The records were obtained from the dissected fascicles i-iii as indicated. The upper and lower traces show the discharges on a fast and slow time base. Middle traces in A-D show ascending volleys recorded from the dissected dorsal funiculi at C3. Time scales in msec. Distances: stimulating electrodes on the nerves - C7 dorsal root entrance, 11.5 cm; C7 dorsal root entrance - recording p!ace, 4.5 cm. (From Holmqvist et al., 1963.)
The records in Fig. 3 were obtained in the same experiment but on stimulation of forelimb nerves. Tracts in the dorsal and intermediate fascicles were activated monosynaptically only from ipsilateral nerves. Stimulation of contralateral nerves produced no discharge in the dorsal fascicle and only a small discharge in the intermediate fascicle. Presumably this discharge was partly, at least, due to inclusion of ventrally located, crossed tracts. The ventral fascicle contained tracts which were monosynaptically activated from contralateral nerves. Stimulation of contralateral nerves evoked large, and stimulation of ipsilateral n:rves small polysynaptic discharges in this fascicle (Holmqvist et al., 1963). Rderences p . 1751176
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The results of the experiment illustrated in Figs. 2 and 3, together with other experiments, indicate that uncrossed tracts, at the cervical level, occupy approximately the dorsal third of the lateral funiculus when originating from the lumbar intumescence and approximately the dorsal two thirds when originating from the cervical intumescence. Tracts activated f r o m afferents in sacral and caudal roots Afferents belonging to sacral roots differ from afferents in most other segments by terminating not only ipsilaterally but also contralaterally in the grey matter. This has been shown histologically by Sprague (1 958) and, correspondingly, motoneurones in the sacral cord have been observed to receive monosynaptic excitation from contralateral afferents (Curtis et al., 1958; Frank and Sprague, 1959). L7
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Fig. 4. Discharges recorded at the first lumbar segment from tracts activated by stimulation of ipsilateral and contralateral L7 and S3 dorsal roots. Cat. The records were obtained from fascicles i-iv as indicated. The ingoing volley was recorded triphasically from the dorsal funiculus at the L7 level (upper traces in A-D). The pairs of traces show the discharges recorded simultaneously on a fast and slow time base. The distance between the two recording sites was 6.5 cm. (From Holmqvist and Oscarsson, 1963.)
The discharges evoked in ascending spinal tracts by stimulation of lumbar, sacral, and caudal roots have been investigated in the cat (Holmqvist and Oscarsson, 1963). Fig. 4 shows an experiment in which four fascicles were dissected at the upper lumbar level and the L7 and S3 dorsal roots prepared for stimulation. A volley in the L7 root evoked discharges with a pattern conforming to that produced by stimulation of hindlimb nerves. Large discharges were evoked by ipsilateral volleys in the two dorsal fascicles (A, E), whereas contralateral volleys were largely ineffective (C, G). In the two ventral fascicles monosynaptic discharges were evoked from contralateral nerves (K, 0).The small monosynaptic discharge (I) evoked from the ipsilateral root in fascicle (iii) was due to some uncrossed fibres included in this fascicle. Similar
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observations were made on stimulation of other lumbar roots and of the sacral roots down to, and sometimes including S2. On the other hand, stimulation of the lower sacral and the caudal roots produced, in the dorsal fascicles, small contralateral discharges with distinct monosynaptic components. This is shown for the S3 dorsal root in Fig. 4, D and H. It is reasonable to explain these discharges as due to activation of uncrossed tracts from contralaterally terminating primary afferents. Recording from dissected fascicles in birds and amphibians
The organization of ascending tracts described above seems to apply generally to the mammalian cord (Magni and Oscarsson, 1962). Experiments made on birds and amphibians suggest that a similar organization exists in all higher vertebrates. The records in Fig. 5 were obtained from three fascicles dissected at the cervical IPSIL. SCIATIC
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Fig. 5. Discharges evoked in tracts ascending in the fascicles (i-iii) indicated in the diagram on stimulation of ipsilateral and contralateral sciatic and radial nerves. Duck, mid-cervical level. Upper and lower traces were taken simultaneously at different speeds. Time scales in msec. Distances: stimulating electrode on sciatic nerve - spinal cord, 7 cm; spinal cord - recording site, 29 cm; stimulating electrode on radial nerve - spinal cord, 6.5 cm; spinal cord - recording site, 16 cm. (From Oscarsson et at., 1963a.)
level in a duck. Leg (sciatic) and wing (radial) nerves were stimulated as indicated. In the dorsomedial fascicle (i) stimulation of ipsilateral nerves evoked large discharges, whereas stimulation of contralateral nerves produced no trace of activity. The discharge evoked from the wing nerve had a distinct monosynaptic component. In the dorsolateral fascicle (ii) large mono- and polysynaptic discharges were evoked from contralateral nerves. Ipsilateral nerves evoked polysynaptic activity and a trace of a monosynaptic response from the radial nerve. In the large ventral fascicle (iii) only small discharges were observed. However, in other experiments with recording from the ventral quadrant of the cord distinct monosynaptic responses were evoked from contralateral, but not from ipsilateral nerves. The results indicate a similar References p . 17511 76
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organization as in mammals but the uncrossed tracts occupy only a small dorsal part of the lateral funiculus (Oscarsson et a/., 1963a). The records shown in Fig. 6 were obtained from the thoracic cord of the frog. Records A and B were obtained from the dissected 'cord-half' (except dorsal funiculus) and show that stimulation of ipsilateral as wcll as contralateral nerves evoked disIPSILda
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Fig. 6 . Distribution of ipsilateral and contralateral discharges in the lateral and ventral funiculi. Frog. (A-D) Discharges recorded from the dissected cord-half (except dorsal funiculus, see diagram) at mid-thoracic level on stimulation of ipsilateral (A, C) and contralateral (B, D) sciatic nerve a t 18 times threshold. Upper and lower traces show the ascending discharge a t different speeds, middle traces show the incoming volley recorded, at the fast speed, from the dorsal roots 15 mm more caudally. A and B were obtained before and C and D, after the lesion shown in the diagram (hatched). The voltage scale applies to the lower traces. E-H illustrate a different experiment. The records show discharges recorded from the dissected ventral quadrant of the cord (see diagram) at the upper thoracic level on stimulation of the ipsilateral and contralateral sciatic nerve a t 20 times threshold. A and B were obtained beforc and G and H after the lesion shown in the diagram (hatched). Conventions as in A-D. (From Oscarsson and Rosen, 1963.)
charges. These discharges were initiated by monosynaptic components. After a lesion that destroyed the ventral quadrant of the cord, only stimulation of ipsilateral nerves evoked a discharge ( C , D). Records E-H are from a different experiment. The ventral quadrant was dissected for recording. Volleys in ipsilateral and contralateral nerves evoked mono- and polysynaptic discharges. Following the lateral lesion indicated in the diagram, only contralateral nerves were effective (G, H). These and other experiments suggest that uncrossed tracts in the frog spinal cord occupy the whole lateral funiculus and crossed tracts approximately the ventral quadrant. This organization is essentially the same as that in mammals and birds, but the uncrossed and crossed tracts occupy largely overlapping areas (Oscarsson and Rosin, 1963). Unit discharge in ascending tracts
Ascending spinal tracts activated from hindlimb afferents have been investigated extensively with microelectrode recording from single fibres in the lateral and ventral
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funiculi of the cat. The observations made during these investigations confirm those made on mass discharge recording and give some additional information. A . Distribution of monosynaptic excitation Readily observable monosynaptic activation occurs only in some ascending tracts and it is possible that monosynaptic excitation from primary afferents is lacking in other tracts (cf. Lundberg and Oscarsson, 1960, 1961, 1962a, b). Among monosynaptically activated tracts the dorsal and ventral spino-cerebellar tracts (DSCT and VSCT) are especially well known. Units belonging to the DSCT and VSCT can be distinguished by their connections with primary afferents and by their mode of termination in the cerebellar cortex (Lundberg and Oscarsson, 1962a). Though DSCT and VSCT fibres largely occupy separate areas in the dorsal and ventral part of the white matter, there is some intermingling in a border zone and a few fibres of either tract may be found displaced deep into the area occupied by the other tract (Oscarsson, 1957; Lundberg and Oscarsson, 1962a). Hence the location of the fibres in the white matter is unsuitable as a criterion for distinguishing DSCT and VSCT axons. Several hundreds of DCST units identified by their connections with primary afferents and by their mode of termination in the cerebellum have been studied. Among these units only two were monosynaptically activated from contralateral instead of ipsilateral nerves (Lundberg and Oscarsson, 1960).Comparable observations have been made with VSCT units (Lundberg and Oscarsson, 1962a). For example, in one investigation 2 out of 61 units were monosynaptically activated from ipsilateral instead of contralateral nerves. These observations indicate that the vast majority of the DSCT neurones have uncrossed axons and the vast majority of VSCT neurones, crossed axons. However, exceptionally a DSCT axon may cross to the other side of the cord, or a VSCT axon ascend without crossing. Presumably the latter cases should be regarded as aberrancies with little functional significance. They give, however, information about the effectiveness of the mechanisms that during the development guide the growth of axons along certain paths. The information concerning units in other tracts is less detailed. However, the spino-cervical tract which ascends in the lateral funiculus dorsally of the DSCT and terminates i n the lateral cervical nucleus, is monosynaptically activated by ipsilateral but not contralateral cutaneous afferents as shown b3th on mass discharge and unit recording (Lundbxg and Oscarsson, 1961 ; Holmqvist and Oscarsson, 1963). Very recently a spino-cerebellar tract (RSCT) activated from group I afferents in ipsilateral forelimb nerves has been discovered (Holmqvist et al., 1963; Oscarsson and Uddenberg, unpublished). There is no trace of monosynaptic mass discharge on stimulation of group I afferents in contralateral nerves. Tentatively, it might be hypothesized that individual tracts consist of either uncrossed or crossed units but not of both.
B. Distribution of polysynaptic excitation Units bslonging to dorsally located tracts are, as a rule, polysynaptically activated References p. 17511 76
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only from ipsilateral nerves. No exceptions have been noted with units in the DSCT or spino-cervical tract but some fibres belonging to a tract with unknown termination sometimes discharge a few impulses 10-30 msec following stimulation of contralateral nerves (Lundberg and Oscarsson, 1960, 1961). This late discharge is presumably due to weak excitation exerted through long chains of interneurones. Recording from units in ventrally located tracts has presented a more varied picture. Three groups of ascending axons with different functional characteristics have been recognized (Lundborg and Oscarsson, 1962a, b). Units belonging to all three groups receive strong polysynaptic excitation or inhibition from contralateral afferents which may be connected with the assumed contralateral location of the cell bodies. Polysynaptic activation from ipsilateral nerves has been observed in all the groups. In the VSCT excitation and inhibition from ipsilateral nerves is weaker than from contralateral nerves (Oscarsson, 1957; Lundberg and Oscarsson, 1962a). Of the other two pathways, provisionally denoted the bilateral and the contralateral ventral flexor reflex tracts (bVFRT and cVFRT), the former receives equally strong excitation from ipsilateral and contralateral nerves, whereas units belonging to the latter tract are either weakly or not at all activated from ipsilateral nerves (Lundberg and Oscarsson, 1962b). DISCUSSION
The main findings described in this paper can be summarized as follows: (1) Tracts in the dorsal part of the ventrolateral white matter are mono- and polysynaptically activated only from ipsilateral nerves. (2) Tracts in the ventral part of the ventrolateral white matter are monosynaptically activated only from contralateral nerves and polysynaptically, both from ipsilateral and contralateral nerves. In most spinal segments primary afferents terminate almost exclusively on the ipsilateral side. This has been shown in histological investigations on the mammalian cord (Schimert, 1939; Escolar, 1948; Liu, 1956; Sprague, 1958) and recently also in investigations on the amphibian cord (W. W. Chambers and C.-N. Liu, personal communication). Hence the findings described under (1) and (2) suggest that dorsal tracts originate from ipsilateral cell bodies and ventral tracts, from contralateral cell bodies, i.e. they are uncrossed and crossed tracts respectively. Similar findings have been made in mammalian, avian, and amphibian species suggesting a basically similar organization in all higher vertebrates. The spinal cord sectors containing uncrossed and crossed tracts vary at different levels of the cord and in different groups of animals, as is illustrated in Fig. 7. The vertically hatched areas contain uncrossed tracts and the horizontally hatched areas, crossed tracts. There is little overlapping of the areas containing uncrossed and crossed tracts arising from the same segmental level in mammals and birds. Some overlapping at the lumbar level has been observed in the cat (Holmqvist and Oscarsson, 1963) and may also occur at other levels, but this overlapping is much smaller than that found in the frog. The uncrossed and crossed tracts are distinguished not only by their differential location in the white matter but also by their polysynaptic connections with primary
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Fig. 7. Spinal cord sectors containing uncrossed (vertical hatching) and crossed (horizontal hatching) ascending tracts at indicated segmental levels. The various diagrams refer to tracts activated from hindlimb and forelimb nerves as indicated.
afferents: the uncrossed tracts are polysynaptically activated only from ipsilateral afferentr and the crossed tracts both from contralateral and ipsilateral afferents. This might suggest that the cell bodies of uncrossed and crossed tracts are located in different regions of the grey matter. Tlus assumption receives some support from the location of the cell columns that have so far been identified as the origin of some individual tracts. The cell columns of uncrossed tracts are vertically hatched and those of crossed tracts horizontally hatched in Fig. 8.4. The dorsal spino-cerebellar tract (DSCT) originates from cells in Clarke’s column (e.g. Jansen and Brodal, 1958) and the spino-cervical tract (SCT) from cells in the head of the dorsal horn (Eccles et ~7/., 1960; Wall, 1960; Lundberg and Oscarsson, 1961). The cell bodies of the ventral spino-cerebellar tract (VSCT) occur in the lateral part of the intermediate zone and the lateral parts of the base and neck of the dorsal horn (Hubbard and Oscarsson, 1962). These cells are presumably distinct from the border cells of Cooper and Sherrington (1940) which occur in ‘the ventrolateral fringe of the spinal grey matter’ (cf. Hubbard and Oscarsson, 1962). Axons of the spinal border cells ascend in the contralateral ventral quadrant of the cord and their function is unknown (cf., however, Sprague, 1953). Our observations suggest that ascending spinal tracts are organized as shown schematically in Fig. 8B. The figure refers to the lumbar region of the mammalian cord but the organization would be essentially the same at other levels of the cord and in other classes of higher vertebrates. The uncrossed tracts ascend in the dorsal part of the lateral funiculus and the crossed tracts ventrally thereof. The cell bodies of uncrossed tracts occur in the dorsomedial part of the grey matter and those of crossed tracts in the ventrolateral part: the borderline is tentatively drawn as suggested References p . 1751176
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Fig. 8. (A). Location of cell columns giving rise to uncrossed (vertical hatching) and crossed (horizontal hatching) ascending tracts. To the former tracts belong the spino-cervical tract (SCT) and the dorsal spino-cerebellar tract (DSCT) and to the latter, the ventral spino-cerebellar tract (VSCT) and the tract of unknown function and termination originating from the spinal border cells (BC) of Cooper and Sherrington (1940). (B). Organization of uncrossed and crossed tracts according to the hypothesis outlined in the text. Tracts ascending in the dorsal part of the lateral funiculus originate from ipsilateral cells in a dorsomedial region of the grey matter. These cells receive terminals from ipsilateral primary afferents and ipsilateral interneurones. Tracts ascending in the ventral part of the cord originate from contralateral cells in a ventrolateral region of the grey matter. These cells receive terminals from ipsilateral primary afferents and have connections with ipsilateral as well as contralateral interneurones. The borderline between the two regions in the grey matter is tentatively drawn (broken line) as suggested by the cell collumns shown in A. (Modified from Magni and Oscarsson, 1962.)
by the location of the cell columns shown in Fig. 8A. Polysynaptic paths from primary afferents to tract cells are drawn as disynaptic. Only the cells of crossed tracts are innervated by interneurones conveying excitation from contralateral afferents. There are no observations in our experiments that contradict the hypothesis illustrated in Fig. 8B. However, some limitations of the evidence should be noted. 1. The recording methods select pathways containing relatively coarse fibres. It seems, however, unlikely that long, thin-fibred pathways would have a different organization, the more so as the tracts investigated constitute a variety of pathways with diverse function and termination. 2. Our identification of uncrossed and crossed tracts depends on the demonstration of monosynaptic connections with primary afferents. Some tracts do not receive any appreciable monosynaptic excitation and can not be identified as crossed or uncrossed with our method. However, in all except one case, these tracts receive polysynaptic excitation predominantly or exclusively from primary afferents entering the cord ipsilaterally of the assumed cell bodies. The exceptional tract receives equally strong excitation from ipsilateral and contralateral afferents (Oscarsson, 1958 ; Lundberg and Oscarsson, 1962b). It is, at present, impossible to say if this ventrally located tract has its cell bodies on the contralateral side in conformity with the present hypothesis. 3. The observation that crossed tracts have a bilateral receptive field might have exceptions. Clinical observations on chordotomy cases suggest that the spino-thalamic
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tract has a purely contralateral receptive field (e.g. Hyndman and Wolkin, 1943; Stookey, 1943). Fibres of this tract might have been missed in our experiments on the cat because of their small size or there might be species differences. 4. The suggestion that the cell bodies of uncrossed and crossed tracts occupy different regions of the grey matter obviously needs anatomical confirmation. SUMMARY
Recent investigations have disclosed that the long ascending spinal tracts in mammals, birds, and presumably also amphibians are organized as follows: 1. Tracts in the dorsal part of the ventrolateral white matter are mono- and polysynaptically activated only from ipsilateral nerves. 2. Tracts in the ventral part of the ventrolateral whte matter are monosynaptically activated only from contralateral nerves and polysynaptically, both from ipsilateral and contralateral nerves. These observations and histological evidence that primary afferents, in most spinal segments, terminate almost exclusively on the ipsilateral side show that the former tracts are uncrossed and the latter crossed at the spinal level. The boundary between uncrossed and crossed tracts is usually sharp but its position varies at different levels of the cord (Fig. 7). It is suggested that the differential organization of uncrossed and crossed tracts is related to a differential location of the cell bodies in the grey matter of the cord. The uncrossed tracts are assumed to originate from cells in the dorsomedial, and the crossed tracts from cells in the ventrolateral part of the grey matter (Fig. 8A, B). Only the cells of the crossed tracts are innervated by interneurones conveying excitation from contralateral afferents (Fig. 8B). REFERENCES COOPER,S., AND SHERRINGTON, CH. S., (1940); Gower’s tract and spinal border cells. Brain, 63, 123-134. CURTIS,D. R., KRNJEVIC, K., AND MILEDI,R., (1958); Crossed inhibition of sacral motoneurones. J . Neurophysiol., 21, 3 19-326. ECCLES,J. C., ECCLES,R. M., AND LUNDBERG, A., (1960); Types of neurones in and around the intermediate nucleus of the lumbo-sacral cord. J . Physiol. (Lond.), 154, 89-1 14. ESCOLAR, J., (1948); The afferent connections of the lst, 2nd, and 3rd cervical nerves in the cat. J . comp. Neurol., 89, 79-92. FRANK, K., AND SPRAGUE, J. M., (1959); Direct contralateral inhibition in the lower sacral spinal cord. Exp. Neurol., 1, 2843. HOLMQVIST, B., AND OSCARSSON, O., (1 963); Location, course, and characteristics of uncrossed and crossed ascending spinal tracts in the cat. Acta physiol. scand., 58, 57-67. HOLMQVIST, B., OSCARSSON, O., AND UDDENBERG, N., (1963); Organization of ascending spinal tracts activated from forelimb afferents in the cat. Acta physiol. scand., 58, 68-76. HUBBARD, J. I., AND OSCARSSON, O., (1962); Localization of the cell bodies of the ventral spinocerebellar tract in lumbar segments of the cat. J . cornp. Neurol., 118, 199-204. HYNDMAN, 0. R., AND WOLKIN,J., (1943); Anterior chordotomy; further observations on physiologic results and optimum manner of performance. Arch. Neurol. Psychiat. (Chic.), 50, 129-148. JANSEN, J., UND BRODAL, A., (1958); Handbuch der mikroskopischen Anatomie des Menschen. IVj8. Das Kleinhirn. Berlin, Springer-Verlag.
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LAPORTE, Y . , LUNDBERG, A., AND OSCARSSON, O., (1956); Functional organization of the dorsal spino-cerebellar tract in the cat. I. Recording of mass discharge in dissected Flechsig’s fasciculus. Acta physiol. scand., 36, 115-187. Lru, C.-N., (1956); Afferent nerves to Clarke’s column and the lateral cuneate nuclei in the cat. Arch. Neurol. Psychiat. (Chic.), 15, 61-17. LUNDBERG, A., AND OSCARSSON, O., (1960); Functional organization of the dorsal spino-cerebellar tract in the cat. VII. Identification of units by antidromic activation from the cerebellar cortex with recognition of five functional subdivisions. Acta physiol. scand., 50, 356-374. LUNDBERG, A., AND OSCARSSON, O., (1961); Three ascending spinal pathways in the dorsal part of the lateral funiculus. Acta physiol. scand., 51, 1-16. LUNDBERG, A., AND OSCARSSON, O., (1962a); Functional organization of the ventral spino-cerebellar tract in the cat. IV. Identification of units by antidromic activation from the cerebellar cortex. Acta physiol. scand., 51, 252-269. LUNDBERG, A., AND OSCARSSON, O., (1962b); Two ascending spinal pathways in the ventral part of the cord. Acta physiol. scand., 51,270-286. MACNI,F., AND OSCARSSON, O., (1962); Principal organization of coarse-fibred ascending spinal tracts in phalanger, rabbit, and cat. Acta physiol. scand., 51, 53-64. OSCARSSON, O., (1957); Functional organization of the ventral spino-cerebellar tract in the cat. 11. Connections with muscle, joint, and skin nerve afferents and effects on adequate stimulation of various receptors. Acta physiol. scanrl., 42, Suppl. 146, 1-107. OSCARSSON, O., (1958) ; Further observations on ascending spinal tracts activated from muscle, joint, and skin nerves. Arch. iral. Biol., 96, 199-215. OSCARSSON, O., AND ROSEN,I., (1963); Organization of ascending tracts in the spinal cord of the frog. Acta physiol. scand. 59, 154-160. OSCARSSON, O., R O S ~ NI., , AND UDDENBERG, N., (1963a); Organization of ascending tracts in the spinal cord of the duck. Acta physiol. scand., 59, 143-153. OSCARSSON, O., ROSEN,I., AND UDDENBERG, N., (1963b); A comparative study of ascending spinal tracts activated from hindlimb afferents in monkey and dog. Arch. ital. Bid., in press. RUDIN,D. O., AND EISENMAN, G . , (1951); A method for dissection and electrical study in vitro of mammalian central nervous tissue. Science, 114, 300-302. SCHIMERT, J., (1939); Das Verhalten der Hinterwurzelkollateralen im Riickenmark. Z. Anat. Entwickl. Cesch., 109, 665-687. SPRAGUE, J. M., (1953); Spinal ‘border cells’ and their role in postural mechanism. J . Neurophysiol., 16, 464474. SPRAGUE, J. M., (1958); The distribution of dorsal root fibres on motor cells in the lumbosacral spinal cord of the cat, and the site of excitatory and inhibitory terminals in monosynaptic pathways. Proc. roy. SOC.B, 149, 534-556. STOOKEY, B., (1943); The management of intractable pain by chordotomy. Ass. Res. nerv. Dis. Proc., 23, 416433. WALL,P. D., (1960); Cord cells responding to touch, damage, and temperature o f skin. J . Neurophy~iol.,23, 197-210. DISCUSSION
NIEUWENHUYS: In the terminology of Cajal your findings can be summarized 1 think as follows: Funicular cells are located in the dorsal part of the gray matter, whereas the commissural occupy the ventral part of the gray matter. I think this thesis fits in well with the anatomical evidence now available. However, there is one exception. In all vertebrates there has been described a spino-bulbar, spino-mesencephalic, resp. spino-thalamic tract, originating from cells in the dorsal horn and constituting the so-called ventral arcuate system (‘Bogenfasern’ of His). I think there are two possibilities: (a) This system consists of thin fibers, and (b) this system does not constitute a long ascending tract, or even: it may not exist at all in the adult stage.
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SZENTAGOTHAI : The only explanation from anatomical viewpoint, that I could think of, is that there is no such thing as the classical concept of a spino-thalamic tract arising from the dorsal horn and immediately crossing in the anterior white commissure. One can cut away horizontally the whole dorsal horn at the level of the dorsal commissure, or place small lesions into the dorsal horn, without getting the slightest signs of degeneration in the same or the next upper segments of fibers within the anterior commissure. Whenever the lesion reaches the intermediate gray matter, i.e. the lamina V1 of Rexed, one immediately gets degenerated fibers in the anterior white commissure. This fits exactly with the location by Oscarsson of cells giving rise to VSCT fibers. After lesions placed into laminae VI and VII we were able to trace degenerated fibers in the cerebellum in the projection area of the VSCT terminating as mossy fibers. Similar lesions give also rise to terminal degeneration of few fibers in the ventrolateral basal nucleus of the contralateral thalamus. Thus there are real spino-thalamic fibers coming from lower lumbar or upper sacral segments, but they arise not from the dorsal horn, but from the intermediate region and central parts of the ventral horn. KUYPERS:I feel that in regard t o the spinal cord and the ascending pathways your paper has been a revolutionary one. The problem of the descending influences on ascending conduction is now more easy to understand. It has always been claimed that the reticular formation has an important influence upon the ascending conduction. Assuming that the ascending fibers came primarily from the dorsal horn, I could not find anatomically any reasonable pathway which would be able to influence the ascending conduction. However, we made the restriction that if this descending influence upon the ascending conduction was exerted, it had to be exerted first and foremost by cells located in the medial part of the intermediate zone and a part of the ventral horn, for this was the place where the prime determination of descending fibers from the reticular formation took place. It is now most gratifying to see that instead of having the origin of the crossed ascending pathways in the posterior horn, you are placing it precisely in the area which is so open to influences of the reticular formation. I think this has cleared the issue, at least for my feeling, considerably. SPRAGUE: I agree with Dr. Oscarsson that the cells giving rise to the ventral spinocerebellar tract are indeed different from the border cells, i n contrast to the original supposition of Cooper and Sherrington. Just what the border cells give rise to, what sort of a tract, is not clear to me although I could make some comments that might be instructive. Firstly: in Nauta-preparations large neurons in the same area as you have placed the origin of the crossed ventral spino-cerebellar tract receive a rich dorsal root input which would accord with the monosynaptic activation of that pathway. However these particular cells are receiving the input from the ipsilateral dorsal root which does not accord so well. Is that correct?
OSCARSSON : This is exactly in accordance with our observations: primary afferents
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make synaptic contacts only with ipsilateral cell bodies. It was in relation to the crossed VSCT fibers that the monosynaptic excitation was described as contralateral. SPRAGUE:The second point is that cells, lying in the area of the border cells in the cat do not receive any appreciable dorsal root input. They receive input from the reticulospinal pathways, as Dr. Kuypers has described, but this area receives very little dorsal root input.
OSCARSSON: We don’t know which tract these cells give origin to. However, some ascending tracts receive excitation from primary afferents mainly or exclusively through segmental interneurones, as for example the bVFRT and possibly the cVFRT described by Lundberg and Oscarsson (Actaphysiol. scand., 54 (1962) 270). The transmission to these tracts is strongly influenced by descending systems originating in the medulla oblongata.
Differential Course and Organization of Uncrossed and Crossed Long Ascending Spinal Tracts 0. OSCARSSON Institute of Physiology, University of Lund, Lund (Sweden)
Recent investigations on ascending spinal tracts with electrophysiological technique suggest that uncrossed and crossed tracts differ in two respects (Magni and Oscarsson, 1962; Holmqvist and Oscarsson, 1963): (1) uncrossed tracts are located dorsally of the crossed tracts; (2) uncrossed tracts are polysynaptically activated only from ipsilateral nerves and crossed tracts both from contralateral and ipsilateral nerves. Furthermore, some evidence suggests that the cell bodies of uncrossed and crossed tracts occupy different areas in the grey matter. The identification of uncrossed and crossed tracts has been based on the hlstological finding that, in most spinal cord segments, primary afferents terminate exclusively, or almost exclusively, on the ipsilateral side (Schimert, 1939; Escolar, 1948; Liu, 1956; Sprague, 1958). Hence, tracts activated monosynaptically from ipsilateral afferents are uncrossed and tracts activated monosynaptically from contralateral afferents, crossed at the spinal level. METHODS
The results were obtained on electrical stimulation of nerves or dorsal roots. The activity evoked in ascending tracts was recorded either as a mass discharge led from dissected fascicles of the spinal cord or studied by intra-axonal recording from single fibres. Of these two methods the former warrants a more detailed description. The technique of recording from isolated strands of the cord was devised by Rudin and Eisenman (1951) for the study of properties of fibres in the cord. It was developed further and used extensively for studying the functional organization of various ascending tracts by Laporte et al. (1956), Lundberg and Oscarsson (1961), and Holmqvist and Oscarsson (1963). The fascicles are prepared as follows. The spinal cord is transected and one pair of roots severed caudally of the transection. The dorsal funiculi are stripped off for a distance of about 2 cm in caudal direction. The remaining part of the cord is divided into the midline and the ‘cord-halves’ (except dorsal funiculi) split longitudinally into subdivisions of various sizes, here called ‘fascicles’. The subdividing is done by cutting with a pair of fine scissors. In the cat, four or five fascicles can be made on each side
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without difficulty. The dissected fascicles are mounted on electrodes for monophasic recording of discharges in ascending tracts, one electrode being in contact with the severed end, the other on the dissected part close to its site of separation from the intact cord. The method can be used for determining the exact position of individual tracts with known functional properties: there is remarkably little destruction of ascending fibres during the dissection and the size of the fascicles can be assessed afterwards by histological methods. The main limitation of the method is that potentials due to activity in unmyelinated and thin, myelinated fibres are too small to be detected. The same limitation holds for the other method which has been used: intra-axonal recording from single fibres. Successful impalement occurs very seldom with fibres having a conduction velocity lower than 25-30 mjsec which would correspond to a diameter of 4-5 ,u (assuming that the Hursh factor of 6 is valid in the CNS). RESULTS
Recording from dissected fascicles in mammalian species
The records in Fig. 1 illustrate the differential characteristics of mass discharges evoked in dorsally and ventrally located tracts. Two fascicles were dissected at the upper lumbar level of the spinal cord in a monkey. The transectional areas of the
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Fig. 1. Discharges in ascending spinal tracts evoked by volleys in muscle and skin afferents of ipsilateral and contralateral hindlimb nerves. Monkey. The muscle (hamstring) and skin (lateral sural) nerves were stimulated at a strength of about 20 times threshold. Records E-L were obtained from the dissected fascicles (i) and (ii) as indicated. The upper and lower traces show the discharge recorded simultaneously at two speeds. The ingoing volleys (A-D) were recorded from the dorsal roots 4.2 cm below the cord dissection at mid-L2. The fast time scale applies to A-D and upper traces in E-L. Voltage scale applies to E-L. (From Oscarsson el al., 1963b). References p . 1751176
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fascicles are shown in the diagram. The upper and lower traces in Fig. 1, E-L show the discharges recorded at two speeds and led from the fascicles as indicated. The top traces (A-D) show the ingoing primary afferent volleys recorded triphasically from the dorsal roots about 4 cm more caudally. Tracts ascending in the dorsal fascicle were activated by volleys in muscle (E) and skin (F) afferents of ipsilateral nerves, whereas no trace of activity was evoked from contralateral nerves (G, H). The ventral fascicle contained tracts activated from contralateral as well as ipsilateral nerves. The latency of the initial component of the mass discharges evoked from ipsilateral nerves in the dorsal fascicle (E, F) and from contralateral nerves in the ventral fascicle (K, L) was 1.O-1.4 msec when measured relatively to the ingoing volley. This short latency proves that the transmission was monosynaptic. It can be concluded that the dorsal fascicle contains uncrossed tracts and the ventral fascicle, crossed tracts. On the other hand, there was no evidence for monosynaptic excitation from ipsilateral nerves to tracts in the ventral fascicle. The initial part of the discharges evoked from ipsilateral nerves in this fascicle (I, J) was related to group I1 muscle afferents and low threshold cutaneous afferents. The long latency indicates that the transmission was:poly sy naptic. I PSIL.
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Fig. 2. Discharges recorded at the third cervical segment from tracts activated by stimulation of ipsilateral and contralateral muscle (hamstring) and skin (superficial peroneal) nerves in the hindlimbs. Cat. The records were obtained from fascicles i-iii as indicated. The upper and lower traces show the discharges recorded simultaneously on a fast and slow time base. Middle traces in A-D show ascending volleys recorded from the dissected dorsal funiculi at C3. Time scales in msec. Distance from stimulating electrode on hamstring nerve to C3 about 37 cm. (From Holmqvist and Oscarsson, 1963.)
Similar observations have been made on recording from fascicles dissected in the upper lumbar region of the phalanger, rabbit, cat, dog, and monkey (Magni and Oscarsson, 1962; Holmqvist and Oscarsson, 1963, Oscarsson et al., 1963b). In all these species uncrossed tracts occur in the dorsal half of the lateral funiculus and crossed tracts in the area ventrally thereof. There is little overlap of the areas containing uncrossed and crossed tracts and the boundary between them corresponds approximately to a horizontal line going through the central canal. Recording from fascicles dissected at the cervical level has disclosed that the borderline between uncrossed and crossed tracts varies according to the spinal cord
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level and the segmental origin of the tracts. In the experiment of Fig. 2, made on the cat, three fascicles (i-iii) were dissected at the level of the third cervical segment. Muscle and skin nerves in the hindlimbs were stimulated. The arrangement of the records corresponds to that in the previous figure, except that the middle traces in A-D show the afferent volleys led from the dorsal funiculi dissected for recording at C3. In the dorsal fascicle (i) ipsilateral but not contralateral nerves evoked monoand polysynaptic discharges (A-D). The intermediate and ventral fascicles (ii and iii) contained tracts which received strong excitatory effects from contralateral nerves and weaker effects from ipsilateral nerves. A large monosynaptic discharge was evoked from contralateral group I afferents in the intermediate fascicle (G). Volleys in skin and high threshold muscle afferents in ipsilateral and contralateral nerves evoked a late activity with a latency suggesting polysynaptic excitation (E-L). These observations show that the borderline between uncrossed and crossed ‘hindlimb tracts’ has shifted dorsally at the cervical level when compared with the lumbar level (Holmqvist and Oscarsson, 1963). IPSIL.. MUSCLE
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-Eclrr Fig. 3. Discharges recorded at the third cervical segment from tracts activated by stimulation of ipsilateral and contralateral muscle (deep radial) and skin (superficial radial) nerves in the forelimbs. Cat. The records were obtained from the dissected fascicles i-iii as indicated. The upper and lower traces show the discharges on a fast and slow time base. Middle traces in A-D show ascending volleys recorded from the dissected dorsal funiculi at C3. Time scales in msec. Distances: stimulating electrodes on the nerves - C7 dorsal root entrance, 11.5 cm; C7 dorsal root entrance - recording p!ace, 4.5 cm. (From Holmqvist et al., 1963.)
The records in Fig. 3 were obtained in the same experiment but on stimulation of forelimb nerves. Tracts in the dorsal and intermediate fascicles were activated monosynaptically only from ipsilateral nerves. Stimulation of contralateral nerves produced no discharge in the dorsal fascicle and only a small discharge in the intermediate fascicle. Presumably this discharge was partly, at least, due to inclusion of ventrally located, crossed tracts. The ventral fascicle contained tracts which were monosynaptically activated from contralateral nerves. Stimulation of contralateral nerves evoked large, and stimulation of ipsilateral n:rves small polysynaptic discharges in this fascicle (Holmqvist et al., 1963). Rderences p . 1751176
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The results of the experiment illustrated in Figs. 2 and 3, together with other experiments, indicate that uncrossed tracts, at the cervical level, occupy approximately the dorsal third of the lateral funiculus when originating from the lumbar intumescence and approximately the dorsal two thirds when originating from the cervical intumescence. Tracts activated f r o m afferents in sacral and caudal roots Afferents belonging to sacral roots differ from afferents in most other segments by terminating not only ipsilaterally but also contralaterally in the grey matter. This has been shown histologically by Sprague (1 958) and, correspondingly, motoneurones in the sacral cord have been observed to receive monosynaptic excitation from contralateral afferents (Curtis et al., 1958; Frank and Sprague, 1959). L7
-A -+
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Fig. 4. Discharges recorded at the first lumbar segment from tracts activated by stimulation of ipsilateral and contralateral L7 and S3 dorsal roots. Cat. The records were obtained from fascicles i-iv as indicated. The ingoing volley was recorded triphasically from the dorsal funiculus at the L7 level (upper traces in A-D). The pairs of traces show the discharges recorded simultaneously on a fast and slow time base. The distance between the two recording sites was 6.5 cm. (From Holmqvist and Oscarsson, 1963.)
The discharges evoked in ascending spinal tracts by stimulation of lumbar, sacral, and caudal roots have been investigated in the cat (Holmqvist and Oscarsson, 1963). Fig. 4 shows an experiment in which four fascicles were dissected at the upper lumbar level and the L7 and S3 dorsal roots prepared for stimulation. A volley in the L7 root evoked discharges with a pattern conforming to that produced by stimulation of hindlimb nerves. Large discharges were evoked by ipsilateral volleys in the two dorsal fascicles (A, E), whereas contralateral volleys were largely ineffective (C, G). In the two ventral fascicles monosynaptic discharges were evoked from contralateral nerves (K, 0).The small monosynaptic discharge (I) evoked from the ipsilateral root in fascicle (iii) was due to some uncrossed fibres included in this fascicle. Similar
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observations were made on stimulation of other lumbar roots and of the sacral roots down to, and sometimes including S2. On the other hand, stimulation of the lower sacral and the caudal roots produced, in the dorsal fascicles, small contralateral discharges with distinct monosynaptic components. This is shown for the S3 dorsal root in Fig. 4, D and H. It is reasonable to explain these discharges as due to activation of uncrossed tracts from contralaterally terminating primary afferents. Recording from dissected fascicles in birds and amphibians
The organization of ascending tracts described above seems to apply generally to the mammalian cord (Magni and Oscarsson, 1962). Experiments made on birds and amphibians suggest that a similar organization exists in all higher vertebrates. The records in Fig. 5 were obtained from three fascicles dissected at the cervical IPSIL. SCIATIC
RADIAL
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Fig. 5. Discharges evoked in tracts ascending in the fascicles (i-iii) indicated in the diagram on stimulation of ipsilateral and contralateral sciatic and radial nerves. Duck, mid-cervical level. Upper and lower traces were taken simultaneously at different speeds. Time scales in msec. Distances: stimulating electrode on sciatic nerve - spinal cord, 7 cm; spinal cord - recording site, 29 cm; stimulating electrode on radial nerve - spinal cord, 6.5 cm; spinal cord - recording site, 16 cm. (From Oscarsson et at., 1963a.)
level in a duck. Leg (sciatic) and wing (radial) nerves were stimulated as indicated. In the dorsomedial fascicle (i) stimulation of ipsilateral nerves evoked large discharges, whereas stimulation of contralateral nerves produced no trace of activity. The discharge evoked from the wing nerve had a distinct monosynaptic component. In the dorsolateral fascicle (ii) large mono- and polysynaptic discharges were evoked from contralateral nerves. Ipsilateral nerves evoked polysynaptic activity and a trace of a monosynaptic response from the radial nerve. In the large ventral fascicle (iii) only small discharges were observed. However, in other experiments with recording from the ventral quadrant of the cord distinct monosynaptic responses were evoked from contralateral, but not from ipsilateral nerves. The results indicate a similar References p . 17511 76
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organization as in mammals but the uncrossed tracts occupy only a small dorsal part of the lateral funiculus (Oscarsson et a/., 1963a). The records shown in Fig. 6 were obtained from the thoracic cord of the frog. Records A and B were obtained from the dissected 'cord-half' (except dorsal funiculus) and show that stimulation of ipsilateral as wcll as contralateral nerves evoked disIPSILda
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Fig. 6 . Distribution of ipsilateral and contralateral discharges in the lateral and ventral funiculi. Frog. (A-D) Discharges recorded from the dissected cord-half (except dorsal funiculus, see diagram) at mid-thoracic level on stimulation of ipsilateral (A, C) and contralateral (B, D) sciatic nerve a t 18 times threshold. Upper and lower traces show the ascending discharge a t different speeds, middle traces show the incoming volley recorded, at the fast speed, from the dorsal roots 15 mm more caudally. A and B were obtained before and C and D, after the lesion shown in the diagram (hatched). The voltage scale applies to the lower traces. E-H illustrate a different experiment. The records show discharges recorded from the dissected ventral quadrant of the cord (see diagram) at the upper thoracic level on stimulation of the ipsilateral and contralateral sciatic nerve a t 20 times threshold. A and B were obtained beforc and G and H after the lesion shown in the diagram (hatched). Conventions as in A-D. (From Oscarsson and Rosen, 1963.)
charges. These discharges were initiated by monosynaptic components. After a lesion that destroyed the ventral quadrant of the cord, only stimulation of ipsilateral nerves evoked a discharge ( C , D). Records E-H are from a different experiment. The ventral quadrant was dissected for recording. Volleys in ipsilateral and contralateral nerves evoked mono- and polysynaptic discharges. Following the lateral lesion indicated in the diagram, only contralateral nerves were effective (G, H). These and other experiments suggest that uncrossed tracts in the frog spinal cord occupy the whole lateral funiculus and crossed tracts approximately the ventral quadrant. This organization is essentially the same as that in mammals and birds, but the uncrossed and crossed tracts occupy largely overlapping areas (Oscarsson and Rosin, 1963). Unit discharge in ascending tracts
Ascending spinal tracts activated from hindlimb afferents have been investigated extensively with microelectrode recording from single fibres in the lateral and ventral
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funiculi of the cat. The observations made during these investigations confirm those made on mass discharge recording and give some additional information. A . Distribution of monosynaptic excitation Readily observable monosynaptic activation occurs only in some ascending tracts and it is possible that monosynaptic excitation from primary afferents is lacking in other tracts (cf. Lundberg and Oscarsson, 1960, 1961, 1962a, b). Among monosynaptically activated tracts the dorsal and ventral spino-cerebellar tracts (DSCT and VSCT) are especially well known. Units belonging to the DSCT and VSCT can be distinguished by their connections with primary afferents and by their mode of termination in the cerebellar cortex (Lundberg and Oscarsson, 1962a). Though DSCT and VSCT fibres largely occupy separate areas in the dorsal and ventral part of the white matter, there is some intermingling in a border zone and a few fibres of either tract may be found displaced deep into the area occupied by the other tract (Oscarsson, 1957; Lundberg and Oscarsson, 1962a). Hence the location of the fibres in the white matter is unsuitable as a criterion for distinguishing DSCT and VSCT axons. Several hundreds of DCST units identified by their connections with primary afferents and by their mode of termination in the cerebellum have been studied. Among these units only two were monosynaptically activated from contralateral instead of ipsilateral nerves (Lundberg and Oscarsson, 1960).Comparable observations have been made with VSCT units (Lundberg and Oscarsson, 1962a). For example, in one investigation 2 out of 61 units were monosynaptically activated from ipsilateral instead of contralateral nerves. These observations indicate that the vast majority of the DSCT neurones have uncrossed axons and the vast majority of VSCT neurones, crossed axons. However, exceptionally a DSCT axon may cross to the other side of the cord, or a VSCT axon ascend without crossing. Presumably the latter cases should be regarded as aberrancies with little functional significance. They give, however, information about the effectiveness of the mechanisms that during the development guide the growth of axons along certain paths. The information concerning units in other tracts is less detailed. However, the spino-cervical tract which ascends in the lateral funiculus dorsally of the DSCT and terminates i n the lateral cervical nucleus, is monosynaptically activated by ipsilateral but not contralateral cutaneous afferents as shown b3th on mass discharge and unit recording (Lundbxg and Oscarsson, 1961 ; Holmqvist and Oscarsson, 1963). Very recently a spino-cerebellar tract (RSCT) activated from group I afferents in ipsilateral forelimb nerves has been discovered (Holmqvist et al., 1963; Oscarsson and Uddenberg, unpublished). There is no trace of monosynaptic mass discharge on stimulation of group I afferents in contralateral nerves. Tentatively, it might be hypothesized that individual tracts consist of either uncrossed or crossed units but not of both.
B. Distribution of polysynaptic excitation Units bslonging to dorsally located tracts are, as a rule, polysynaptically activated References p. 17511 76
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only from ipsilateral nerves. No exceptions have been noted with units in the DSCT or spino-cervical tract but some fibres belonging to a tract with unknown termination sometimes discharge a few impulses 10-30 msec following stimulation of contralateral nerves (Lundberg and Oscarsson, 1960, 1961). This late discharge is presumably due to weak excitation exerted through long chains of interneurones. Recording from units in ventrally located tracts has presented a more varied picture. Three groups of ascending axons with different functional characteristics have been recognized (Lundborg and Oscarsson, 1962a, b). Units belonging to all three groups receive strong polysynaptic excitation or inhibition from contralateral afferents which may be connected with the assumed contralateral location of the cell bodies. Polysynaptic activation from ipsilateral nerves has been observed in all the groups. In the VSCT excitation and inhibition from ipsilateral nerves is weaker than from contralateral nerves (Oscarsson, 1957; Lundberg and Oscarsson, 1962a). Of the other two pathways, provisionally denoted the bilateral and the contralateral ventral flexor reflex tracts (bVFRT and cVFRT), the former receives equally strong excitation from ipsilateral and contralateral nerves, whereas units belonging to the latter tract are either weakly or not at all activated from ipsilateral nerves (Lundberg and Oscarsson, 1962b). DISCUSSION
The main findings described in this paper can be summarized as follows: (1) Tracts in the dorsal part of the ventrolateral white matter are mono- and polysynaptically activated only from ipsilateral nerves. (2) Tracts in the ventral part of the ventrolateral white matter are monosynaptically activated only from contralateral nerves and polysynaptically, both from ipsilateral and contralateral nerves. In most spinal segments primary afferents terminate almost exclusively on the ipsilateral side. This has been shown in histological investigations on the mammalian cord (Schimert, 1939; Escolar, 1948; Liu, 1956; Sprague, 1958) and recently also in investigations on the amphibian cord (W. W. Chambers and C.-N. Liu, personal communication). Hence the findings described under (1) and (2) suggest that dorsal tracts originate from ipsilateral cell bodies and ventral tracts, from contralateral cell bodies, i.e. they are uncrossed and crossed tracts respectively. Similar findings have been made in mammalian, avian, and amphibian species suggesting a basically similar organization in all higher vertebrates. The spinal cord sectors containing uncrossed and crossed tracts vary at different levels of the cord and in different groups of animals, as is illustrated in Fig. 7. The vertically hatched areas contain uncrossed tracts and the horizontally hatched areas, crossed tracts. There is little overlapping of the areas containing uncrossed and crossed tracts arising from the same segmental level in mammals and birds. Some overlapping at the lumbar level has been observed in the cat (Holmqvist and Oscarsson, 1963) and may also occur at other levels, but this overlapping is much smaller than that found in the frog. The uncrossed and crossed tracts are distinguished not only by their differential location in the white matter but also by their polysynaptic connections with primary
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HINDLIMB
BIRD LEG
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Fig. 7. Spinal cord sectors containing uncrossed (vertical hatching) and crossed (horizontal hatching) ascending tracts at indicated segmental levels. The various diagrams refer to tracts activated from hindlimb and forelimb nerves as indicated.
afferents: the uncrossed tracts are polysynaptically activated only from ipsilateral afferentr and the crossed tracts both from contralateral and ipsilateral afferents. This might suggest that the cell bodies of uncrossed and crossed tracts are located in different regions of the grey matter. Tlus assumption receives some support from the location of the cell columns that have so far been identified as the origin of some individual tracts. The cell columns of uncrossed tracts are vertically hatched and those of crossed tracts horizontally hatched in Fig. 8.4. The dorsal spino-cerebellar tract (DSCT) originates from cells in Clarke’s column (e.g. Jansen and Brodal, 1958) and the spino-cervical tract (SCT) from cells in the head of the dorsal horn (Eccles et ~7/., 1960; Wall, 1960; Lundberg and Oscarsson, 1961). The cell bodies of the ventral spino-cerebellar tract (VSCT) occur in the lateral part of the intermediate zone and the lateral parts of the base and neck of the dorsal horn (Hubbard and Oscarsson, 1962). These cells are presumably distinct from the border cells of Cooper and Sherrington (1940) which occur in ‘the ventrolateral fringe of the spinal grey matter’ (cf. Hubbard and Oscarsson, 1962). Axons of the spinal border cells ascend in the contralateral ventral quadrant of the cord and their function is unknown (cf., however, Sprague, 1953). Our observations suggest that ascending spinal tracts are organized as shown schematically in Fig. 8B. The figure refers to the lumbar region of the mammalian cord but the organization would be essentially the same at other levels of the cord and in other classes of higher vertebrates. The uncrossed tracts ascend in the dorsal part of the lateral funiculus and the crossed tracts ventrally thereof. The cell bodies of uncrossed tracts occur in the dorsomedial part of the grey matter and those of crossed tracts in the ventrolateral part: the borderline is tentatively drawn as suggested References p . 1751176
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Fig. 8. (A). Location of cell columns giving rise to uncrossed (vertical hatching) and crossed (horizontal hatching) ascending tracts. To the former tracts belong the spino-cervical tract (SCT) and the dorsal spino-cerebellar tract (DSCT) and to the latter, the ventral spino-cerebellar tract (VSCT) and the tract of unknown function and termination originating from the spinal border cells (BC) of Cooper and Sherrington (1940). (B). Organization of uncrossed and crossed tracts according to the hypothesis outlined in the text. Tracts ascending in the dorsal part of the lateral funiculus originate from ipsilateral cells in a dorsomedial region of the grey matter. These cells receive terminals from ipsilateral primary afferents and ipsilateral interneurones. Tracts ascending in the ventral part of the cord originate from contralateral cells in a ventrolateral region of the grey matter. These cells receive terminals from ipsilateral primary afferents and have connections with ipsilateral as well as contralateral interneurones. The borderline between the two regions in the grey matter is tentatively drawn (broken line) as suggested by the cell collumns shown in A. (Modified from Magni and Oscarsson, 1962.)
by the location of the cell columns shown in Fig. 8A. Polysynaptic paths from primary afferents to tract cells are drawn as disynaptic. Only the cells of crossed tracts are innervated by interneurones conveying excitation from contralateral afferents. There are no observations in our experiments that contradict the hypothesis illustrated in Fig. 8B. However, some limitations of the evidence should be noted. 1. The recording methods select pathways containing relatively coarse fibres. It seems, however, unlikely that long, thin-fibred pathways would have a different organization, the more so as the tracts investigated constitute a variety of pathways with diverse function and termination. 2. Our identification of uncrossed and crossed tracts depends on the demonstration of monosynaptic connections with primary afferents. Some tracts do not receive any appreciable monosynaptic excitation and can not be identified as crossed or uncrossed with our method. However, in all except one case, these tracts receive polysynaptic excitation predominantly or exclusively from primary afferents entering the cord ipsilaterally of the assumed cell bodies. The exceptional tract receives equally strong excitation from ipsilateral and contralateral afferents (Oscarsson, 1958 ; Lundberg and Oscarsson, 1962b). It is, at present, impossible to say if this ventrally located tract has its cell bodies on the contralateral side in conformity with the present hypothesis. 3. The observation that crossed tracts have a bilateral receptive field might have exceptions. Clinical observations on chordotomy cases suggest that the spino-thalamic
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tract has a purely contralateral receptive field (e.g. Hyndman and Wolkin, 1943; Stookey, 1943). Fibres of this tract might have been missed in our experiments on the cat because of their small size or there might be species differences. 4. The suggestion that the cell bodies of uncrossed and crossed tracts occupy different regions of the grey matter obviously needs anatomical confirmation. SUMMARY
Recent investigations have disclosed that the long ascending spinal tracts in mammals, birds, and presumably also amphibians are organized as follows: 1. Tracts in the dorsal part of the ventrolateral white matter are mono- and polysynaptically activated only from ipsilateral nerves. 2. Tracts in the ventral part of the ventrolateral whte matter are monosynaptically activated only from contralateral nerves and polysynaptically, both from ipsilateral and contralateral nerves. These observations and histological evidence that primary afferents, in most spinal segments, terminate almost exclusively on the ipsilateral side show that the former tracts are uncrossed and the latter crossed at the spinal level. The boundary between uncrossed and crossed tracts is usually sharp but its position varies at different levels of the cord (Fig. 7). It is suggested that the differential organization of uncrossed and crossed tracts is related to a differential location of the cell bodies in the grey matter of the cord. The uncrossed tracts are assumed to originate from cells in the dorsomedial, and the crossed tracts from cells in the ventrolateral part of the grey matter (Fig. 8A, B). Only the cells of the crossed tracts are innervated by interneurones conveying excitation from contralateral afferents (Fig. 8B). REFERENCES COOPER,S., AND SHERRINGTON, CH. S., (1940); Gower’s tract and spinal border cells. Brain, 63, 123-134. CURTIS,D. R., KRNJEVIC, K., AND MILEDI,R., (1958); Crossed inhibition of sacral motoneurones. J . Neurophysiol., 21, 3 19-326. ECCLES,J. C., ECCLES,R. M., AND LUNDBERG, A., (1960); Types of neurones in and around the intermediate nucleus of the lumbo-sacral cord. J . Physiol. (Lond.), 154, 89-1 14. ESCOLAR, J., (1948); The afferent connections of the lst, 2nd, and 3rd cervical nerves in the cat. J . comp. Neurol., 89, 79-92. FRANK, K., AND SPRAGUE, J. M., (1959); Direct contralateral inhibition in the lower sacral spinal cord. Exp. Neurol., 1, 2843. HOLMQVIST, B., AND OSCARSSON, O., (1 963); Location, course, and characteristics of uncrossed and crossed ascending spinal tracts in the cat. Acta physiol. scand., 58, 57-67. HOLMQVIST, B., OSCARSSON, O., AND UDDENBERG, N., (1963); Organization of ascending spinal tracts activated from forelimb afferents in the cat. Acta physiol. scand., 58, 68-76. HUBBARD, J. I., AND OSCARSSON, O., (1962); Localization of the cell bodies of the ventral spinocerebellar tract in lumbar segments of the cat. J . cornp. Neurol., 118, 199-204. HYNDMAN, 0. R., AND WOLKIN,J., (1943); Anterior chordotomy; further observations on physiologic results and optimum manner of performance. Arch. Neurol. Psychiat. (Chic.), 50, 129-148. JANSEN, J., UND BRODAL, A., (1958); Handbuch der mikroskopischen Anatomie des Menschen. IVj8. Das Kleinhirn. Berlin, Springer-Verlag.
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LAPORTE, Y . , LUNDBERG, A., AND OSCARSSON, O., (1956); Functional organization of the dorsal spino-cerebellar tract in the cat. I. Recording of mass discharge in dissected Flechsig’s fasciculus. Acta physiol. scand., 36, 115-187. Lru, C.-N., (1956); Afferent nerves to Clarke’s column and the lateral cuneate nuclei in the cat. Arch. Neurol. Psychiat. (Chic.), 15, 61-17. LUNDBERG, A., AND OSCARSSON, O., (1960); Functional organization of the dorsal spino-cerebellar tract in the cat. VII. Identification of units by antidromic activation from the cerebellar cortex with recognition of five functional subdivisions. Acta physiol. scand., 50, 356-374. LUNDBERG, A., AND OSCARSSON, O., (1961); Three ascending spinal pathways in the dorsal part of the lateral funiculus. Acta physiol. scand., 51, 1-16. LUNDBERG, A., AND OSCARSSON, O., (1962a); Functional organization of the ventral spino-cerebellar tract in the cat. IV. Identification of units by antidromic activation from the cerebellar cortex. Acta physiol. scand., 51, 252-269. LUNDBERG, A., AND OSCARSSON, O., (1962b); Two ascending spinal pathways in the ventral part of the cord. Acta physiol. scand., 51,270-286. MACNI,F., AND OSCARSSON, O., (1962); Principal organization of coarse-fibred ascending spinal tracts in phalanger, rabbit, and cat. Acta physiol. scand., 51, 53-64. OSCARSSON, O., (1957); Functional organization of the ventral spino-cerebellar tract in the cat. 11. Connections with muscle, joint, and skin nerve afferents and effects on adequate stimulation of various receptors. Acta physiol. scanrl., 42, Suppl. 146, 1-107. OSCARSSON, O., (1958) ; Further observations on ascending spinal tracts activated from muscle, joint, and skin nerves. Arch. iral. Biol., 96, 199-215. OSCARSSON, O., AND ROSEN,I., (1963); Organization of ascending tracts in the spinal cord of the frog. Acta physiol. scand. 59, 154-160. OSCARSSON, O., R O S ~ NI., , AND UDDENBERG, N., (1963a); Organization of ascending tracts in the spinal cord of the duck. Acta physiol. scand., 59, 143-153. OSCARSSON, O., ROSEN,I., AND UDDENBERG, N., (1963b); A comparative study of ascending spinal tracts activated from hindlimb afferents in monkey and dog. Arch. ital. Bid., in press. RUDIN,D. O., AND EISENMAN, G . , (1951); A method for dissection and electrical study in vitro of mammalian central nervous tissue. Science, 114, 300-302. SCHIMERT, J., (1939); Das Verhalten der Hinterwurzelkollateralen im Riickenmark. Z. Anat. Entwickl. Cesch., 109, 665-687. SPRAGUE, J. M., (1953); Spinal ‘border cells’ and their role in postural mechanism. J . Neurophysiol., 16, 464474. SPRAGUE, J. M., (1958); The distribution of dorsal root fibres on motor cells in the lumbosacral spinal cord of the cat, and the site of excitatory and inhibitory terminals in monosynaptic pathways. Proc. roy. SOC.B, 149, 534-556. STOOKEY, B., (1943); The management of intractable pain by chordotomy. Ass. Res. nerv. Dis. Proc., 23, 416433. WALL,P. D., (1960); Cord cells responding to touch, damage, and temperature o f skin. J . Neurophy~iol.,23, 197-210. DISCUSSION
NIEUWENHUYS: In the terminology of Cajal your findings can be summarized 1 think as follows: Funicular cells are located in the dorsal part of the gray matter, whereas the commissural occupy the ventral part of the gray matter. I think this thesis fits in well with the anatomical evidence now available. However, there is one exception. In all vertebrates there has been described a spino-bulbar, spino-mesencephalic, resp. spino-thalamic tract, originating from cells in the dorsal horn and constituting the so-called ventral arcuate system (‘Bogenfasern’ of His). I think there are two possibilities: (a) This system consists of thin fibers, and (b) this system does not constitute a long ascending tract, or even: it may not exist at all in the adult stage.
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SZENTAGOTHAI : The only explanation from anatomical viewpoint, that I could think of, is that there is no such thing as the classical concept of a spino-thalamic tract arising from the dorsal horn and immediately crossing in the anterior white commissure. One can cut away horizontally the whole dorsal horn at the level of the dorsal commissure, or place small lesions into the dorsal horn, without getting the slightest signs of degeneration in the same or the next upper segments of fibers within the anterior commissure. Whenever the lesion reaches the intermediate gray matter, i.e. the lamina V1 of Rexed, one immediately gets degenerated fibers in the anterior white commissure. This fits exactly with the location by Oscarsson of cells giving rise to VSCT fibers. After lesions placed into laminae VI and VII we were able to trace degenerated fibers in the cerebellum in the projection area of the VSCT terminating as mossy fibers. Similar lesions give also rise to terminal degeneration of few fibers in the ventrolateral basal nucleus of the contralateral thalamus. Thus there are real spino-thalamic fibers coming from lower lumbar or upper sacral segments, but they arise not from the dorsal horn, but from the intermediate region and central parts of the ventral horn. KUYPERS:I feel that in regard t o the spinal cord and the ascending pathways your paper has been a revolutionary one. The problem of the descending influences on ascending conduction is now more easy to understand. It has always been claimed that the reticular formation has an important influence upon the ascending conduction. Assuming that the ascending fibers came primarily from the dorsal horn, I could not find anatomically any reasonable pathway which would be able to influence the ascending conduction. However, we made the restriction that if this descending influence upon the ascending conduction was exerted, it had to be exerted first and foremost by cells located in the medial part of the intermediate zone and a part of the ventral horn, for this was the place where the prime determination of descending fibers from the reticular formation took place. It is now most gratifying to see that instead of having the origin of the crossed ascending pathways in the posterior horn, you are placing it precisely in the area which is so open to influences of the reticular formation. I think this has cleared the issue, at least for my feeling, considerably. SPRAGUE: I agree with Dr. Oscarsson that the cells giving rise to the ventral spinocerebellar tract are indeed different from the border cells, i n contrast to the original supposition of Cooper and Sherrington. Just what the border cells give rise to, what sort of a tract, is not clear to me although I could make some comments that might be instructive. Firstly: in Nauta-preparations large neurons in the same area as you have placed the origin of the crossed ventral spino-cerebellar tract receive a rich dorsal root input which would accord with the monosynaptic activation of that pathway. However these particular cells are receiving the input from the ipsilateral dorsal root which does not accord so well. Is that correct?
OSCARSSON : This is exactly in accordance with our observations: primary afferents
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make synaptic contacts only with ipsilateral cell bodies. It was in relation to the crossed VSCT fibers that the monosynaptic excitation was described as contralateral. SPRAGUE:The second point is that cells, lying in the area of the border cells in the cat do not receive any appreciable dorsal root input. They receive input from the reticulospinal pathways, as Dr. Kuypers has described, but this area receives very little dorsal root input.
OSCARSSON: We don’t know which tract these cells give origin to. However, some ascending tracts receive excitation from primary afferents mainly or exclusively through segmental interneurones, as for example the bVFRT and possibly the cVFRT described by Lundberg and Oscarsson (Actaphysiol. scand., 54 (1962) 270). The transmission to these tracts is strongly influenced by descending systems originating in the medulla oblongata.