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The distribution and pattern of axon branching of pyramidal tract cells
484
Brain Research, 57 (1973) 484-491 © ElsevierScientificPublishingCompany, Amsterdam- Printed in The Netherlands
The distribution and paNern of axon branching of pyramidal ~
Ms
K. ENDO. T. ARAKI AND N. YAGI Departments of Physiology and of ( N. Y.) Otolaryngology, Faculty of Medicine, Kyoto University, Kyoto (Japan)
(Accepted April 20th, 1973)
Both anatomicap0As,1s,26, 27 and physiologicall-9,n-14,16,19,21, 22,25,2s studies have shown that the cortical motosensory area projects corticofugal fibers to various subcortical structures in addition to the spinal cord. Whether these projections to subcortical structures are axon collaterals of pyramidal tract cells or independent tracts terminating to particular loci is not always clear, though collateral pyramidal branching has been demonstrated electrophysiologicallyfor projections to the thalamic ventrolateral nucleus5, ventrobasal complex~2, red nucleus25, pontine nucleus~and dorsal column nucleP 4. The aim of the present investigation was to clarify the frequency distribution and the pattern of axon branching of PT cells by analyzing antidromic invasion following stimulation of various subcortical structures. Cats anaesthetized with Nembutal (35-50 mg/kg) and immobilized with gallamine triethiodide were used under artificial ventilation. Stimulating electrodes of concentric or bipolar type were placed stereotaxically in various subcortical structures including the medullary pyramid (at the level of the trapezoid body), cerebral peduncle, internal capsule (CI), head of the caudate nucleus (Cd), putamen (Put), globus pallidus (GP), thalamic nuclei: ventralis anterior (VA); ventralis lateralis (VL); ventratis posterior lateralis (VPL); centrum medianum (CM), red nucleus (RN), mesencephalic reticular formation (RF, dorsal to the red nucleus), pontine nucleus (PN) and dorsal column nuclei (DCN). The stimulating electrodes were all located ipsilateralty to the cortex investigated except for DCN. Additional stimulating electrodes were placed in the contralateral lateral corticospinal tract at the level of the first cervical segment (C1). PT cells in the pre- and postcruciate cortices were penetrated by glass microelectrodes filled with 2 M K-citrate or 0.6 M K~SO4 solution with DC resistances of 20-50 MR. PT cells were identified by antidromic spikes intracellularly recorded following stimulation of the pyramid or Ct. The latter stimulation was always given when collaterals to DCN were investigated. Antidromic activation from other sources via axon collaterals were identified by spike potentials without preceding depolarization and with fixed latencies. Moreover, high frequency stimulation of 100-200/see was routinely used for this identification. In order to exclude antidromic activation due to stimulus spread to the adjacent pyramidal tract, i.e., from stimulating electrodes
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Fig. I. Antidromic spike potentials recorded intracellularly from PT cells following stimulation of subcortical structures. The records were obtained from 3 PT cells (A and B, C-E and F-I). Upper beams in A-E and uppermost beams in F-G give surface potentials recorded in pericruciate region, while middle beams in F-G and upper beams in H-I show potentials recorded in subcortical white matter. A and B: intracellular potentials elicited by stimulation of the cerebral peduncle (A) and VL (B), antidromic and orthodromic spikes being recorded in the latter. C-E: intracellular potentials evoked by stimulation of the peduncle (C), VL (D) and internal capsule adjacent to VL (E). In D, antidromic spikes elicited by weak stimulus (late spikes) and by strong one (early spikes) applied to VL were superimposed. F-I: intracellular potentials produced by stimulation of the pyramid (F, I). RN (H) and cerebral peduncle adjacent to RN (G). Note the difference in time scale between F-G and H-I. located at the basal ganglia and thalamic nuclei to CI and from those at RN, R F and P N to the peduncle, stimulating electrodes were placed appropriately in CI and peduncle adjacent to each nucleus, and differences in latencies of antidromic spikes elicited by stimulation of each nucleus and by stimulation of adjacent pyramidal tract were carefully compared. Fig. 1 shows examples of antidromic spike potentials recorded intracellularly from PT cells with axon collaterals to VL or RN. In record B, 3 sweeps following VL stimulation were superimposed. A spike potential with a latency of 0.60 msec without preceding depolarization and followed by another spike is seen in one sweep, while spike potentials preceded by monosynaptic EPSPs with a latency of 0.88 msec are observed in the other two sweeps. The latency of the earliest spike in B is slightly longer than that elicited by peduncle stimulation (A, 0.54 msec). Since the stimulating
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TABLE I MEAN LATENCIES OF ANTIDROMIC SPIKES OF P T CELLS AND FREQUENCY DISTRIBUTION OF COLLATERAL l ~ r a n ( m n ~
Upper part: mean latencies (msec) of antidromic spikes evoked by stimulation of the respective subcortical structures (numerators) and those of the corresponding adjacent pyramidal tract (denominators). Each number in paren-
thesis gives number of PT cells producing antidromic spikes. Lower part: frequency distribution of axon collaterals to subcortical loci. Each numerator indicates number of PT cells giving axon collaterals to the respective loci, while each denominator gives number of PT cells investigated. See text for explanation of PT cell types. Type o f P T cell
Cd
Put
GP
VA
Mean antidromic latency (msec)
F
0.53/0.29 (7) 1.57/0.82 (2)
0.54/0.32 (5) 1.34/0.85 (2)
0.58/0.35 (2)
0.47/0.32 (5) 1.45/0.91 (2)
Frequency distribution
F
7/104 (6.7%) 2/33 (6.1%) 9/137 (6.6~)
5/91 (5.5 %) 2/24 (8.3 %) 7/115 (6.1 ~o)
2/91 (2,2 ~) 0/24 (0%) 2/115 (1.7~)
5/i 12 (4.5 ~'o) 2/39 (5.1%) 7/t51 (4.6~o)
S
S Total (F + S)
electrode at the peduncle was located about 1 t mm distant from VL in this case, stimulus spread from VL to the adjacent CI, if any, should produce an antidromic spike o f much shorter latency than that in A. On the basis of these results, the earliest spike in B can be assumed to be an antidromic spike attributable to activation o f an axon collateral of this PT cell to VL. Another example of axon collaterals to VL is given in D. Weak stimulation of VL elicited spike potentials with a latency of 0.92 msec that was slightly longer than that evoked by peduncle stimulation (C, 0.82 msec). Increase in the strength of stimulus to VL in D gave rise to a jump of the latency of the spike (0.62 msec). The latency of the early spikes in D was the same as that elicited by adjacent CI stimulation (E). Therefore, the jump of the latency of the spike in D may be attributable to the stimulus spread to CI. Since no EPSP is observed preceding the spikes with longer latency in D, the late spikes in D must be also antidromically evoked by activation of axon collaterals to VL, as in the case of B. An example demonstrating axon collaterals to R N is given in Fig. 1F-I. Antidromic spike potentials elicited by pyramid and peduncle stimulation of this PT cell are shown in F and G respectively. Following R N stimulation antidromic spikes were recorded in about one-third of the traces and EPSPs of presumably disynaptic nature were observed with or without preceding antidromic spikes (H, with slower sweep and higher gain than F and G). That the early spikes in H were antidromic was readily deduced from the absence of any preceding depolarization. Antidromic spikes evoked by pyramid stimulation with the same sweep speed and gain as in H are shown in I. It should be mentioned that the latency of antidromic spikes attributable to the activation of collaterals to R N in H (1.25 msec) is remarkably longer than that evoked by adjacent peduncle stimulation (G, 0.52 msec) or by pyramid stimulation (F and I, 0,76 msec). Differ-
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SHORT COMMUNICATIONS
VL
VPL
CM
RN
RF
PN
DCN
0.50/0.34 (26) 1.84/1.34 (7)
0.53/0.36 (25) 1.25/0.95 (5)
0.83/0.45 (6) 2.48/1.55 (4)
0.87/0.56 (23) 1.83/1.33 (4)
1.02/0.55 (19) 2.28/1.49 (2)
0.94/0.75 (7) 1.56/1.34 (4)
1.57/1.33 (12) 3.89/2.97 (4)
26/138 (18.8~) 7/39 (17.9 ~) 33/177 (18.6~)
25/134 (18.7%) 5/49 (10.2~) 30/183 (16.4~)
6/93 (6.4%) 4/29 (13.8%) 10/122 (8.2~)
23/120 (19.2~) 4/28 (14.3 ~) 27/148 (18.2 ~)
19/107 (17.8 ~) 2/24 (8.3~) 21/131 (16.0~)
7/52 (13.5~) 4/28 (14.3 ~) 11/80 (13.8%)
12/73 (16.4~) 4/27 (14.8 ~) 16/100 (16.0~)
ences in latencies between antidromic spikes elicited by stimulation of various subcortical structures and those evoked by stimulation of adjacent pyramidal tract were fairly large in most cases, as is seen in Fig. 1D-E and G-H. This result suggests that conduction velocities along axon collaterals may be considerably slower than those along parent axons. In some cases, however, differences in these antidromic latencies were small. All the data with the difference less than 0.1 msec, though small in number, were discarded because it was difficult to determine whether antidromic spikes elicited by stimulation of various subcortical structures were due to collateral activation or to stimulus spread to the adjacent pyramidal tract. Though corticonuclear cells projecting to VL, VPL, RN, PN and DCN were occasionally found in the present study, they are not further mentioned in this report. PT cells were classified into fast (F) and slow (S) types according to the axonal conduction velocity measured along the pyramid-peduncle portion: more than 20 m/sec (F) or less than 20 m/sec (S). Collateral branching of PT cells was identified as described above. Mean latencies of antidromic spikes recorded from fast and slow PT cells following stimulation of pyramidal axon collaterals within various subcortical structures and those following stimulation of the corresponding adjacent pyramidal tract are shown in the upper part of Table I. Each numerator gives the former latency, each denominator the latter latency, and each number in parenthesis indicates number of PT cells in which stimulation of the respective nuclei elicited antidromic spikes, i.e., number of PT cells giving axon collaterals. In the case of the dorsal column nuclei, the denominator gives the mean latency of antidromic spikes elicited by stimulation of the first cervical cord. It is seen that considerable time is consumed for the conduction along axon collaterals, particularly in CM, RN and RF.
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It was found that, out of 138 fast and 49 slow PT cells investigated, 92 fast and 27 slow PT cells gave axon collaterals to subcortical structures and 38 fast and 8 slow PT cells projected to two or three different subcortical loci branching from single axons. The frequency distribution of collateral branching to subcortical structures is shown in the lower part of Table I. Each numerator gives number of PT cells, the axons of which branch off to the respective nuclei, while each denominator indicates number of PT cells investigated. Since stimulating electrodes were not always placed in all subcortical structures listed in Table I in every experiwient, the denominator in each column is not all the same. As is seen in Table I, frequencies of collateral branching to VL, VPL, RN, RF, PN and D C N were relatively high and those to Cd, Put, VA and CM were moderate. On the other hand, collaterals to GP were very few. Although the number of slow PT cells investigated was relatively small, frequencies of collateral branching between fast and slow PT cells may be compared. No great difference was found in frequencies of collateral branching to Cd, Put, VA, VL, RN, PN and D C N between fast and slow PT cells, while collaterals to RF and VPL were more frequently encountered with fast PT cells than with slow ones and the reverse relationship was found in the case of collaterals to CM. PT cells giving axon collaterals to V L, Cd or RF were located relatively more abundantly in the precruciate cortex than in the postcruciate, while those to VPL or D C N were predominant in the postcruciate region. PT cells projecting axon collaterals to CM, RN or PN were found with approximately equal frequency in both the precruciate and postcruciate. Although many axon collaterals might be missed because stimulating electrodes were not always placed in all subcortical structres listed in Table I in every experiment, and although stimulating electrodes were lacking in the lower brain stem region except D C N and bilateral projections were not examined, it was possible to find out the general pattern of frequent combinations of collaterals to different subcortical structures branching from single pyramidal axons. A total of 38 combinations of collateral branching to two subcortical structures and of 8 combinations to 3 subcortical loci were obtained in the present study. Each combination of collaterals to 3 loci in 8 PT cells was divided into 3 combinations of collaterals to two subcortical loci and consequently 62 (38 q- 8 × 3) combinations to two loci were obtained. The most frequently observed combinations were found to be VPL + D C N and VL + RN. Combinations found in more than two cases were gathered and 55 combinations to two subcortical loci thus selected were classified into several groups as shown in Table II. Subcortical loci were classified conveniently into (a) basal ganglia (Cd, Put and GP) and VA, (b) nuclei concerning cerebral-cerebellar-cerebral circuit (VL, R N and PN), (c) specific sensory relay nuclei (VPL and DCN) and (d) non-specific system (CM, R F and VA), and combinations o f a ÷ b, within b, b + d, within c, c ÷ d or within d, and c q- b were grouped in columns A, B, C, D, E and F of Table II respectively. Combinations of VA were used doubly in columns A and C, and C and E. Each combination of collaterals to 3 subcortical structures is given in an appropriate group in the original form. As is seen in this table, fairly frequent occurrences were found not only in combination within motor and sensory systems respectively but also in combined projections to motor and sensory systems.
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The present results suggest that P T cells f u n c t i o n in a complex m a n n e r with feedback systems t h r o u g h subcortical levels, cooperating with i n h i b i t o r y and excitatory a c t i o n o f recurrent axon collaterals o f fast a n d slow PT cells respectivelylV,23.~L a n d that s h a r p distinction between the p y r a m i d a l a n d extrapyramidal systems may be impossible f r o m a physiological p o i n t of view. F u r t h e r m o r e , it may be suggested that there are several f u n c t i o n a l types o f P T cells according to the p a t t e r n of collateral b r a n c h i n g to subcortical structures, in a d d i t i o n to the fast and slow types. O u r results are i n c o m p a t i b l e with the reports that cortical n e u r o n s projecting to VL were n o n - P T cells 4, a n d t h a t corticofugal cells to D C N were i n d e p e n d e n t o f the corticospinal tract cells 9. The discrepancy in the f o r m e r case m a y be due in part to the a s s u m p t i o n that cortical units r e s p o n d i n g to VL s t i m u l a t i o n at less t h a n 0.8 msec were classified as a n t i d r o m i c , a n d t h a t in the latter case m a y be due to somewhat different location o f the cortical area investigated or to the small n u m b e r o f cells examined.
1 ALBE-FESSARD D., ET GILLETT, E., Convergences d'aff6rences d'origines corticale et p6riph6rique
vers le centre m6dian du chat anesth6si6 ou 6veilt6, Electroenceph. clin. NeurophysioL, 13 (1961) 257-269. 2 ALLEN,G. I,, KORN, H., AND OSHIMA,T., Monosynaptic pyramidal activation of pontine nuclei cells projecting to the cerebellum, Brain Research, 15 (1969) 272-275. 3 ANDERSEN, P., ECCLES, J. C., SCHMIDT, R. F., AND YOKOTA, T., Slow potential waves produced in the cuneate nucleus by cutaneaus volleys and by cortical stimulation, J. Neurophysiol., 27 (1964) 78-91. 4 BLUM,B., HALPERN,L. M., AND WARD, JR., A. A., Microelectrode studies of the afferent connections and efferent projections of neurons in the sensorimotor cortex of the cat, Exp. Neurol., 20 (1968) 156-173. 5 CLARE,M. H., LANDAU,W. M., ANDBISHOP,G. H., Electrophysiological evidence of a collateral pathway from the pyramidal tract to the thalamus in the cat, Exp. Neurol., 9 (1964) 262-267. 6 DARIAN-SMITH, I., AND YOKOTA, T., Corticofugal effects on different neuron types within the cat's brain stem activated by tactile stimulation of the face, J. Neurophysiol., 29 (1966) 185-206. 7 DORMONT,J. F., AND MASSION, J., Duality of cortical control on ventrolateral thalamic activity, Exp. Brain Res., 10 (1970) 205-218. 8 FRENCH,J. D., HERN~NDEZ-PE6N,R., AND LIVINGSTON, R. B., Projections from cortex to cephalic brain stem (reticular formation) in monkey, J. Neurophysiol., 18 (1955) 74-95. 9 GORDON, G., AND MILLER, R., Identification of cortical cells projecting to the dorsal column nuclei of the cat, Quart. J. exp. PhysioL, 54 (1969) 85-98. 10 KUYPERS,H. G. J. M., ANDTUERK,J. O., The distribution of the cortical fibres within the nuclei cuneatus and gracilis in the cat, J. Anat. (Lond.), 98 (1964) 143-162. l l LEVITT, M., CARREAS,M., LIU, C. N., AND CHAMBERS,W. W., Pyramidal and extrapyramidal modulation of somatosensory activity in gracile and cuneate nuclei, Arch. itaL Biol., 102 (1964) 197-229. 12 MAGNI,F., MELZACK,R., MORUZZI,G., AND SMITH,C. J., Direct pyramidal influences on the dorsal-column nuclei, Arch. ital. BioL, 97 (1959) 357-377. 13 MAGNI,F., AND WILLIS, W. D., Cortical control of brain stem reticular neurons, Arch. ital. BioL, 102 (1964) 418-433. 14 McCOMAS,A. J., AND WILSON, P., An investigation of pyramidal tract cells in the somatosensory cortex of the rat, J. Physiol. (Lond.), 194 (1968) 271-288. 15 NIIMI, K., KISHI,S., MIKI, M., AND FUJITA, S., An experimental study of the course and termination of the projection fibers from cortical areas 4 and 6 in the cat, Folia psychiat, neurol, jap., 17 (1963) 167-216. 16 OGDEN, T. E., Cortical control of thalamic somato-sensory relay nuclei, Electroenceph. clin. Neurophysiol., 12 (1960) 621-634. 17 PHILLIPS,C. G., Actions ofantidromic pyramidal volleys on single BETZ cells in the cat, Quart. J. exp. PhysioL, 44 (1959) 1-25.
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491
18 RINVIK,E., The corticothalamic projection from the pericruciate and coronal gyri in the cat. An experimental study with silver-impregnation methods, Brain Research, 10 (1968) 79-119. 19 ROCHA-MIRANDA,C. E., Single unit analysis of cortex-caudate connections, Electroenceph. clin. Neurophysiol., 19 (1965) 237-247. 20 RossL G. F., ANDBRODAL,A., Corticofugal fibers to the brain-stem reticular formation. An experimental study in the cat, J. Anat. (Lond.), 90 (1956) 42-62. 21 SAKATA,H., ISHmMA,T., ANDTOYODA,Y., Single unit studies on ventrolateral nucleus of the thalamus in cat: its relation to the cerebellum, motor cortex and basal ganglia, Jap. J. Physiol., 16 (1966) 42-60. 22 SHIMAZC, H., YANAGISAWA,N., AND GAROUTTE, B., Cortico-pyramidal influences on thalamic somatosensory transmission in the cat, Jap. J. Physiol., 15 (1965) 101-124. 23 STEFANIS,C., AND JASPER, H., Recurrent collateral inhibition in pyramidal tract neurons, J. Neurophysiol., 27 (1964) 855-877. 24 TAKAHASHI,K., KUBOTA,K., AND UNO, M., Recurrent facilitation in cat pyramidal tract cells, J. NeurophysioL, 30 (1967) 22-34. 25 TSUKAHARA,N., FULLER, D. R. G., AND BROOKS,V. B., Collateral pyramidal influences on the corticorubrospinal system, J. NeurophysioL, 31 (1968) 467-484. 26 WALBERG,F., Corticofugal fibres to the nuclei of the dorsal columns. An experimental study in the cat, Brain, 80 (1957) 273-287. 27 WEBSTER,K. E., The cortico-striatal projection in the cat, J. Anat. (Lond.), 99 (1965) 329-337. 28 WIESENDANGER,M., The pyramidal tract. Recent investigations on its morphology and function, Ergebn. PhysioL, 61 (1969) 72-136.
Brain Research, 57 (1973) 484-491 © ElsevierScientificPublishingCompany, Amsterdam- Printed in The Netherlands
The distribution and paNern of axon branching of pyramidal ~
Ms
K. ENDO. T. ARAKI AND N. YAGI Departments of Physiology and of ( N. Y.) Otolaryngology, Faculty of Medicine, Kyoto University, Kyoto (Japan)
(Accepted April 20th, 1973)
Both anatomicap0As,1s,26, 27 and physiologicall-9,n-14,16,19,21, 22,25,2s studies have shown that the cortical motosensory area projects corticofugal fibers to various subcortical structures in addition to the spinal cord. Whether these projections to subcortical structures are axon collaterals of pyramidal tract cells or independent tracts terminating to particular loci is not always clear, though collateral pyramidal branching has been demonstrated electrophysiologicallyfor projections to the thalamic ventrolateral nucleus5, ventrobasal complex~2, red nucleus25, pontine nucleus~and dorsal column nucleP 4. The aim of the present investigation was to clarify the frequency distribution and the pattern of axon branching of PT cells by analyzing antidromic invasion following stimulation of various subcortical structures. Cats anaesthetized with Nembutal (35-50 mg/kg) and immobilized with gallamine triethiodide were used under artificial ventilation. Stimulating electrodes of concentric or bipolar type were placed stereotaxically in various subcortical structures including the medullary pyramid (at the level of the trapezoid body), cerebral peduncle, internal capsule (CI), head of the caudate nucleus (Cd), putamen (Put), globus pallidus (GP), thalamic nuclei: ventralis anterior (VA); ventralis lateralis (VL); ventratis posterior lateralis (VPL); centrum medianum (CM), red nucleus (RN), mesencephalic reticular formation (RF, dorsal to the red nucleus), pontine nucleus (PN) and dorsal column nuclei (DCN). The stimulating electrodes were all located ipsilateralty to the cortex investigated except for DCN. Additional stimulating electrodes were placed in the contralateral lateral corticospinal tract at the level of the first cervical segment (C1). PT cells in the pre- and postcruciate cortices were penetrated by glass microelectrodes filled with 2 M K-citrate or 0.6 M K~SO4 solution with DC resistances of 20-50 MR. PT cells were identified by antidromic spikes intracellularly recorded following stimulation of the pyramid or Ct. The latter stimulation was always given when collaterals to DCN were investigated. Antidromic activation from other sources via axon collaterals were identified by spike potentials without preceding depolarization and with fixed latencies. Moreover, high frequency stimulation of 100-200/see was routinely used for this identification. In order to exclude antidromic activation due to stimulus spread to the adjacent pyramidal tract, i.e., from stimulating electrodes
485
SHORT COMMUNICATIONS
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Fig. I. Antidromic spike potentials recorded intracellularly from PT cells following stimulation of subcortical structures. The records were obtained from 3 PT cells (A and B, C-E and F-I). Upper beams in A-E and uppermost beams in F-G give surface potentials recorded in pericruciate region, while middle beams in F-G and upper beams in H-I show potentials recorded in subcortical white matter. A and B: intracellular potentials elicited by stimulation of the cerebral peduncle (A) and VL (B), antidromic and orthodromic spikes being recorded in the latter. C-E: intracellular potentials evoked by stimulation of the peduncle (C), VL (D) and internal capsule adjacent to VL (E). In D, antidromic spikes elicited by weak stimulus (late spikes) and by strong one (early spikes) applied to VL were superimposed. F-I: intracellular potentials produced by stimulation of the pyramid (F, I). RN (H) and cerebral peduncle adjacent to RN (G). Note the difference in time scale between F-G and H-I. located at the basal ganglia and thalamic nuclei to CI and from those at RN, R F and P N to the peduncle, stimulating electrodes were placed appropriately in CI and peduncle adjacent to each nucleus, and differences in latencies of antidromic spikes elicited by stimulation of each nucleus and by stimulation of adjacent pyramidal tract were carefully compared. Fig. 1 shows examples of antidromic spike potentials recorded intracellularly from PT cells with axon collaterals to VL or RN. In record B, 3 sweeps following VL stimulation were superimposed. A spike potential with a latency of 0.60 msec without preceding depolarization and followed by another spike is seen in one sweep, while spike potentials preceded by monosynaptic EPSPs with a latency of 0.88 msec are observed in the other two sweeps. The latency of the earliest spike in B is slightly longer than that elicited by peduncle stimulation (A, 0.54 msec). Since the stimulating
486
SHORT COMMUNICATIONS
TABLE I MEAN LATENCIES OF ANTIDROMIC SPIKES OF P T CELLS AND FREQUENCY DISTRIBUTION OF COLLATERAL l ~ r a n ( m n ~
Upper part: mean latencies (msec) of antidromic spikes evoked by stimulation of the respective subcortical structures (numerators) and those of the corresponding adjacent pyramidal tract (denominators). Each number in paren-
thesis gives number of PT cells producing antidromic spikes. Lower part: frequency distribution of axon collaterals to subcortical loci. Each numerator indicates number of PT cells giving axon collaterals to the respective loci, while each denominator gives number of PT cells investigated. See text for explanation of PT cell types. Type o f P T cell
Cd
Put
GP
VA
Mean antidromic latency (msec)
F
0.53/0.29 (7) 1.57/0.82 (2)
0.54/0.32 (5) 1.34/0.85 (2)
0.58/0.35 (2)
0.47/0.32 (5) 1.45/0.91 (2)
Frequency distribution
F
7/104 (6.7%) 2/33 (6.1%) 9/137 (6.6~)
5/91 (5.5 %) 2/24 (8.3 %) 7/115 (6.1 ~o)
2/91 (2,2 ~) 0/24 (0%) 2/115 (1.7~)
5/i 12 (4.5 ~'o) 2/39 (5.1%) 7/t51 (4.6~o)
S
S Total (F + S)
electrode at the peduncle was located about 1 t mm distant from VL in this case, stimulus spread from VL to the adjacent CI, if any, should produce an antidromic spike o f much shorter latency than that in A. On the basis of these results, the earliest spike in B can be assumed to be an antidromic spike attributable to activation o f an axon collateral of this PT cell to VL. Another example of axon collaterals to VL is given in D. Weak stimulation of VL elicited spike potentials with a latency of 0.92 msec that was slightly longer than that evoked by peduncle stimulation (C, 0.82 msec). Increase in the strength of stimulus to VL in D gave rise to a jump of the latency of the spike (0.62 msec). The latency of the early spikes in D was the same as that elicited by adjacent CI stimulation (E). Therefore, the jump of the latency of the spike in D may be attributable to the stimulus spread to CI. Since no EPSP is observed preceding the spikes with longer latency in D, the late spikes in D must be also antidromically evoked by activation of axon collaterals to VL, as in the case of B. An example demonstrating axon collaterals to R N is given in Fig. 1F-I. Antidromic spike potentials elicited by pyramid and peduncle stimulation of this PT cell are shown in F and G respectively. Following R N stimulation antidromic spikes were recorded in about one-third of the traces and EPSPs of presumably disynaptic nature were observed with or without preceding antidromic spikes (H, with slower sweep and higher gain than F and G). That the early spikes in H were antidromic was readily deduced from the absence of any preceding depolarization. Antidromic spikes evoked by pyramid stimulation with the same sweep speed and gain as in H are shown in I. It should be mentioned that the latency of antidromic spikes attributable to the activation of collaterals to R N in H (1.25 msec) is remarkably longer than that evoked by adjacent peduncle stimulation (G, 0.52 msec) or by pyramid stimulation (F and I, 0,76 msec). Differ-
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SHORT COMMUNICATIONS
VL
VPL
CM
RN
RF
PN
DCN
0.50/0.34 (26) 1.84/1.34 (7)
0.53/0.36 (25) 1.25/0.95 (5)
0.83/0.45 (6) 2.48/1.55 (4)
0.87/0.56 (23) 1.83/1.33 (4)
1.02/0.55 (19) 2.28/1.49 (2)
0.94/0.75 (7) 1.56/1.34 (4)
1.57/1.33 (12) 3.89/2.97 (4)
26/138 (18.8~) 7/39 (17.9 ~) 33/177 (18.6~)
25/134 (18.7%) 5/49 (10.2~) 30/183 (16.4~)
6/93 (6.4%) 4/29 (13.8%) 10/122 (8.2~)
23/120 (19.2~) 4/28 (14.3 ~) 27/148 (18.2 ~)
19/107 (17.8 ~) 2/24 (8.3~) 21/131 (16.0~)
7/52 (13.5~) 4/28 (14.3 ~) 11/80 (13.8%)
12/73 (16.4~) 4/27 (14.8 ~) 16/100 (16.0~)
ences in latencies between antidromic spikes elicited by stimulation of various subcortical structures and those evoked by stimulation of adjacent pyramidal tract were fairly large in most cases, as is seen in Fig. 1D-E and G-H. This result suggests that conduction velocities along axon collaterals may be considerably slower than those along parent axons. In some cases, however, differences in these antidromic latencies were small. All the data with the difference less than 0.1 msec, though small in number, were discarded because it was difficult to determine whether antidromic spikes elicited by stimulation of various subcortical structures were due to collateral activation or to stimulus spread to the adjacent pyramidal tract. Though corticonuclear cells projecting to VL, VPL, RN, PN and DCN were occasionally found in the present study, they are not further mentioned in this report. PT cells were classified into fast (F) and slow (S) types according to the axonal conduction velocity measured along the pyramid-peduncle portion: more than 20 m/sec (F) or less than 20 m/sec (S). Collateral branching of PT cells was identified as described above. Mean latencies of antidromic spikes recorded from fast and slow PT cells following stimulation of pyramidal axon collaterals within various subcortical structures and those following stimulation of the corresponding adjacent pyramidal tract are shown in the upper part of Table I. Each numerator gives the former latency, each denominator the latter latency, and each number in parenthesis indicates number of PT cells in which stimulation of the respective nuclei elicited antidromic spikes, i.e., number of PT cells giving axon collaterals. In the case of the dorsal column nuclei, the denominator gives the mean latency of antidromic spikes elicited by stimulation of the first cervical cord. It is seen that considerable time is consumed for the conduction along axon collaterals, particularly in CM, RN and RF.
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It was found that, out of 138 fast and 49 slow PT cells investigated, 92 fast and 27 slow PT cells gave axon collaterals to subcortical structures and 38 fast and 8 slow PT cells projected to two or three different subcortical loci branching from single axons. The frequency distribution of collateral branching to subcortical structures is shown in the lower part of Table I. Each numerator gives number of PT cells, the axons of which branch off to the respective nuclei, while each denominator indicates number of PT cells investigated. Since stimulating electrodes were not always placed in all subcortical structures listed in Table I in every experiwient, the denominator in each column is not all the same. As is seen in Table I, frequencies of collateral branching to VL, VPL, RN, RF, PN and D C N were relatively high and those to Cd, Put, VA and CM were moderate. On the other hand, collaterals to GP were very few. Although the number of slow PT cells investigated was relatively small, frequencies of collateral branching between fast and slow PT cells may be compared. No great difference was found in frequencies of collateral branching to Cd, Put, VA, VL, RN, PN and D C N between fast and slow PT cells, while collaterals to RF and VPL were more frequently encountered with fast PT cells than with slow ones and the reverse relationship was found in the case of collaterals to CM. PT cells giving axon collaterals to V L, Cd or RF were located relatively more abundantly in the precruciate cortex than in the postcruciate, while those to VPL or D C N were predominant in the postcruciate region. PT cells projecting axon collaterals to CM, RN or PN were found with approximately equal frequency in both the precruciate and postcruciate. Although many axon collaterals might be missed because stimulating electrodes were not always placed in all subcortical structres listed in Table I in every experiment, and although stimulating electrodes were lacking in the lower brain stem region except D C N and bilateral projections were not examined, it was possible to find out the general pattern of frequent combinations of collaterals to different subcortical structures branching from single pyramidal axons. A total of 38 combinations of collateral branching to two subcortical structures and of 8 combinations to 3 subcortical loci were obtained in the present study. Each combination of collaterals to 3 loci in 8 PT cells was divided into 3 combinations of collaterals to two subcortical loci and consequently 62 (38 q- 8 × 3) combinations to two loci were obtained. The most frequently observed combinations were found to be VPL + D C N and VL + RN. Combinations found in more than two cases were gathered and 55 combinations to two subcortical loci thus selected were classified into several groups as shown in Table II. Subcortical loci were classified conveniently into (a) basal ganglia (Cd, Put and GP) and VA, (b) nuclei concerning cerebral-cerebellar-cerebral circuit (VL, R N and PN), (c) specific sensory relay nuclei (VPL and DCN) and (d) non-specific system (CM, R F and VA), and combinations o f a ÷ b, within b, b + d, within c, c ÷ d or within d, and c q- b were grouped in columns A, B, C, D, E and F of Table II respectively. Combinations of VA were used doubly in columns A and C, and C and E. Each combination of collaterals to 3 subcortical structures is given in an appropriate group in the original form. As is seen in this table, fairly frequent occurrences were found not only in combination within motor and sensory systems respectively but also in combined projections to motor and sensory systems.
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490
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The present results suggest that P T cells f u n c t i o n in a complex m a n n e r with feedback systems t h r o u g h subcortical levels, cooperating with i n h i b i t o r y and excitatory a c t i o n o f recurrent axon collaterals o f fast a n d slow PT cells respectivelylV,23.~L a n d that s h a r p distinction between the p y r a m i d a l a n d extrapyramidal systems may be impossible f r o m a physiological p o i n t of view. F u r t h e r m o r e , it may be suggested that there are several f u n c t i o n a l types o f P T cells according to the p a t t e r n of collateral b r a n c h i n g to subcortical structures, in a d d i t i o n to the fast and slow types. O u r results are i n c o m p a t i b l e with the reports that cortical n e u r o n s projecting to VL were n o n - P T cells 4, a n d t h a t corticofugal cells to D C N were i n d e p e n d e n t o f the corticospinal tract cells 9. The discrepancy in the f o r m e r case m a y be due in part to the a s s u m p t i o n that cortical units r e s p o n d i n g to VL s t i m u l a t i o n at less t h a n 0.8 msec were classified as a n t i d r o m i c , a n d t h a t in the latter case m a y be due to somewhat different location o f the cortical area investigated or to the small n u m b e r o f cells examined.
1 ALBE-FESSARD D., ET GILLETT, E., Convergences d'aff6rences d'origines corticale et p6riph6rique
vers le centre m6dian du chat anesth6si6 ou 6veilt6, Electroenceph. clin. NeurophysioL, 13 (1961) 257-269. 2 ALLEN,G. I,, KORN, H., AND OSHIMA,T., Monosynaptic pyramidal activation of pontine nuclei cells projecting to the cerebellum, Brain Research, 15 (1969) 272-275. 3 ANDERSEN, P., ECCLES, J. C., SCHMIDT, R. F., AND YOKOTA, T., Slow potential waves produced in the cuneate nucleus by cutaneaus volleys and by cortical stimulation, J. Neurophysiol., 27 (1964) 78-91. 4 BLUM,B., HALPERN,L. M., AND WARD, JR., A. A., Microelectrode studies of the afferent connections and efferent projections of neurons in the sensorimotor cortex of the cat, Exp. Neurol., 20 (1968) 156-173. 5 CLARE,M. H., LANDAU,W. M., ANDBISHOP,G. H., Electrophysiological evidence of a collateral pathway from the pyramidal tract to the thalamus in the cat, Exp. Neurol., 9 (1964) 262-267. 6 DARIAN-SMITH, I., AND YOKOTA, T., Corticofugal effects on different neuron types within the cat's brain stem activated by tactile stimulation of the face, J. Neurophysiol., 29 (1966) 185-206. 7 DORMONT,J. F., AND MASSION, J., Duality of cortical control on ventrolateral thalamic activity, Exp. Brain Res., 10 (1970) 205-218. 8 FRENCH,J. D., HERN~NDEZ-PE6N,R., AND LIVINGSTON, R. B., Projections from cortex to cephalic brain stem (reticular formation) in monkey, J. Neurophysiol., 18 (1955) 74-95. 9 GORDON, G., AND MILLER, R., Identification of cortical cells projecting to the dorsal column nuclei of the cat, Quart. J. exp. PhysioL, 54 (1969) 85-98. 10 KUYPERS,H. G. J. M., ANDTUERK,J. O., The distribution of the cortical fibres within the nuclei cuneatus and gracilis in the cat, J. Anat. (Lond.), 98 (1964) 143-162. l l LEVITT, M., CARREAS,M., LIU, C. N., AND CHAMBERS,W. W., Pyramidal and extrapyramidal modulation of somatosensory activity in gracile and cuneate nuclei, Arch. itaL Biol., 102 (1964) 197-229. 12 MAGNI,F., MELZACK,R., MORUZZI,G., AND SMITH,C. J., Direct pyramidal influences on the dorsal-column nuclei, Arch. ital. BioL, 97 (1959) 357-377. 13 MAGNI,F., AND WILLIS, W. D., Cortical control of brain stem reticular neurons, Arch. ital. BioL, 102 (1964) 418-433. 14 McCOMAS,A. J., AND WILSON, P., An investigation of pyramidal tract cells in the somatosensory cortex of the rat, J. Physiol. (Lond.), 194 (1968) 271-288. 15 NIIMI, K., KISHI,S., MIKI, M., AND FUJITA, S., An experimental study of the course and termination of the projection fibers from cortical areas 4 and 6 in the cat, Folia psychiat, neurol, jap., 17 (1963) 167-216. 16 OGDEN, T. E., Cortical control of thalamic somato-sensory relay nuclei, Electroenceph. clin. Neurophysiol., 12 (1960) 621-634. 17 PHILLIPS,C. G., Actions ofantidromic pyramidal volleys on single BETZ cells in the cat, Quart. J. exp. PhysioL, 44 (1959) 1-25.
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491
18 RINVIK,E., The corticothalamic projection from the pericruciate and coronal gyri in the cat. An experimental study with silver-impregnation methods, Brain Research, 10 (1968) 79-119. 19 ROCHA-MIRANDA,C. E., Single unit analysis of cortex-caudate connections, Electroenceph. clin. Neurophysiol., 19 (1965) 237-247. 20 RossL G. F., ANDBRODAL,A., Corticofugal fibers to the brain-stem reticular formation. An experimental study in the cat, J. Anat. (Lond.), 90 (1956) 42-62. 21 SAKATA,H., ISHmMA,T., ANDTOYODA,Y., Single unit studies on ventrolateral nucleus of the thalamus in cat: its relation to the cerebellum, motor cortex and basal ganglia, Jap. J. Physiol., 16 (1966) 42-60. 22 SHIMAZC, H., YANAGISAWA,N., AND GAROUTTE, B., Cortico-pyramidal influences on thalamic somatosensory transmission in the cat, Jap. J. Physiol., 15 (1965) 101-124. 23 STEFANIS,C., AND JASPER, H., Recurrent collateral inhibition in pyramidal tract neurons, J. Neurophysiol., 27 (1964) 855-877. 24 TAKAHASHI,K., KUBOTA,K., AND UNO, M., Recurrent facilitation in cat pyramidal tract cells, J. NeurophysioL, 30 (1967) 22-34. 25 TSUKAHARA,N., FULLER, D. R. G., AND BROOKS,V. B., Collateral pyramidal influences on the corticorubrospinal system, J. NeurophysioL, 31 (1968) 467-484. 26 WALBERG,F., Corticofugal fibres to the nuclei of the dorsal columns. An experimental study in the cat, Brain, 80 (1957) 273-287. 27 WEBSTER,K. E., The cortico-striatal projection in the cat, J. Anat. (Lond.), 99 (1965) 329-337. 28 WIESENDANGER,M., The pyramidal tract. Recent investigations on its morphology and function, Ergebn. PhysioL, 61 (1969) 72-136.