- Email: [email protected]
Sensorimotor cortical projections to the marginal zone of the trigeminal subnucleus caudalis
Brain Research, 232 (1982) 171-176 Elsevier Biomedical Press
171
Sensorimotor cortical projections to the marginal zone of the trigeminal subnucleus caudalis
ROBERT C. DUNN, Jr.* and KOK LEONG CHONG Division of Neurosurgery and Department of Anatomy, St. Louis University School of Medicine, St. Louis, MO 63104 (U.S.A.)
(Accepted October 15th, 1981) Key words: spinal trigeminal nucleus - - spinal trigeminal subnucleus caudalis - - electron microscopy pain pathways - - endogenous analgesia systems - - corticobulbar pathways -
-
An ultrastructural investigation of the marginal zone (lamina I) of the spinal trigeminal subnucleus caudalis was carried out in 7 adult cats at 30 h through 7 days after ablations of face area of the contralaterai sensorimotor cortex. Corticofugal boutons were observed to undergo electrondense degeneration in the marginal zone beginning 4 days after the cortical lesion. These boutons were small (1-2 #m), widely dispersed and made synaptic contacts onto small dendrites or dendritic spines. These new observations indicate that cortical inhibition and facilitation of ascending orofacial sensation may be mediated in part by a direct pathway to the marginal zone. There has been renewed interest in neuroanatomic substrates for pain transmission and modulation, particularly the descending endogenous analgesia systems projecting f r o m the brain stem (e.g. from the periaqueductal gray and the nucleus raphe magnus1,9). In contrast, the neuroanatomic organization of the descending pathways from the somatosensory cortex, also known to be effective in modifying transmission of noxious and non-noxious sensory information 4,5,19, has received less attention recently. To clarify the topography of the corticotrigeminal pathway in adult cats for ongoing developmental and plasticity studies, we have completed a light microscopic investigation of the projection from the coronal gyrus (face area of primary somatosensory cortex 23) to the spinal trigeminal (V) nucleus 6. Observations in this study suggested a cortical projection to the marginal zone of the spinal V subnucleus caudalis. Marginal zone neurons in the spinal V caudalis have been shown to respond specifically to noxious and non-noxious stimuli 15,1~ and these cells are also known to project to the thalamus2, a. Therefore, a cortical projection to the marginal zone would represent a potential anatomical substrate for the cortical modulation of ascending orofacial sensation. Furthermore, information about the synaptology of cortical afferents within the marginal zone would be expected to increase the understanding of mechanisms underlying such cortical effects. We report here the prelimi* Address for correspondence: Department of Anatomy, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, U.S.A. 0006-8993/82/0000-0000/$02.75 © Elsevier Biomedical Press
72
173 nary results of an ultrastructural study of the corticotrigeminal projection to the spinal V subnucleus caudalis. The findings suggest that the face area of primary sensorimotor cortex does project to the marginal zone of subnucleus caudalis in the cat. Seven healthy adult cats with normal dentition were used for this investigation. After anesthetization with ketamine hydrochloride (33 mg/kg i.m.), these animals underwent frontal craniectomy to expose the left coronal gyrus. Coronal cortex ablations were then made with electrocautery followed by aspiration. Lesions were carefully restricted to the coronal gyrus and were limited in depth to minimize inadvertent damage to underlying white matter pathways from other gyri. Following survival periods of from 30 h to 7 days (chosen to minimize likelihood of central V transganglionic degeneration 21 - - see below) the experimental animals were reanesthetized with an overdose of ketamine and underwent perfusion with 1 ~ paraformaldehyde, 1.5 ~o glutaraldehyde in a 0.15 M sodium diphosphate buffer. Transverse tissue sections from the brain stem were then processed for electron microscopy according to the methods of Sotelo and Palay z0. Sections from subnucleus caudalis contralateral to the cortical lesions were examined in J O E L 100 CX electron microscope. The electron microscopic studies of the marginal zone by Kerr 11,12, Gobel and Hockfield s and, most recently, the detailed quantitative studies by Ralston 17, have documented the ultrastructural features which characterize the marginal zone (lamina 1 of Rexed18). These major identifying characteristics include: (1) a band of neuropil 40-150 # m in width exhibiting an abundance of small terminals, most of which contain round vesicles, some with dense cores; (2) a fine meshwork of small myelinated axons; and (3) two neuronal types: one small (10-15/tm), the other large (20-30 #m) marginal cells of Waldeyer irregularly scattered throughout lamina I. In this study electron-dense corticotrigeminal terminals became apparent in the marginal zone of subnucleus caudalis four days following contralateral coronal gyrus
Fig. 1. Low power electron photomicrograph from marginal zone of subnucleus caudalis 5 days following contralateral coronal gyrus ablation. Two axon terminals undergoing dense degeneration (DTs) are indicated by arrows. These are immediately adjacent to the spinal trigeminal tract (STT). Fig. 2 illustrates another section through terminal on left at greater magnification. Scale bar equals 5 /~m. Animal RD 97. Fig. 2. Terminal undergoing electron-dense degeneration (DT) in the marginal zone of subnucleus caudalis. Higher magnification of another section through terminal on left in Fig. 1. Alterations in synaptic vesicles (V) are evident. Two asymmetric synaptic contacts onto a small dendrite (arrowheads) are present. Scale bar equals 0.5/~m. Animal RD 97. Fig. 3. Degenerating bouton from the marginal zone 5 days following contralateral coronal gyrus ablation. Marked irregularity of the contours of the bouton and alteration in vesicle shape and size (V) is evident. Arrowheads indicate asymmetric synapse onto a small dendritic profile. An adjacent profile containing pleomorphic vesicles may be making synaptic contact onto degenerating cortical bouton (*). Scale bar equals 0.5 #m. Animal RD 169. Fig. 4. An electron-dense cortical bouton with altered vesicles (V) displays highly scalloped outlines which extend between adjacent profiles. Five-day survival. Scale bar equals 0.5/~m. Animal RD 97. Fig. 5. An electron-dense degenerating terminal (DT) from the nucleus proprius. Arrowheads indicate asymmetric synaptic contacts onto primary dendrite (D). Five-day survival. Scale bar equals 1/~m. Animal RD 169.
174 ablation (animals RD 156 and 165). These cortical boutons were found widely dispersed throughout the width of the marginal zone from areas immediately adjacent to the spinal V tract (Fig. 1) to the outermost portions of the underlying substantia gelatinosa. These dark endings were few in number but, when encountered, tended to occur in small clusters of two or three. To date, only electron-dense degeneration has been observed and this became most marked five days after injury (RD 97 and 169). Figs. 1-4 illustrate typical examples of degenerating cortical boutons in the marginal zone of two animals (RD 97 and 169) which had undergone contralateral cortical ablation 5 days prior to sacrifice. As shown, the darkened terminals in the marginal zone were typically small (1-2/zm) and contained round, clear vesicles; occasional degenerating profiles also included a few dense core vesicles. These distorted boutons made synaptic contact with small (1-2/zm) dendrites or dendritic spines (Figs. 2 and 3). As yet, cortical boutons have not been seen making axosomatic contact with marginal neurons, nor have they been found as the presynaptic profile in axoaxonic arrangements. By 7 days after cortical ablation, fewer degenerating boutons were seen but darkened, thinly myelinated axons were readily found from 4 through 7 days survival in the marginal zone and its extensions into the spinal V tract. Occasional degenerating cortical terminals have been observed in the nucleus proprius (magnocellular nucleus) of caudalis. Here electron-dense terminals appeared to synapse onto dendrites of a distinctly larger size than those seen in the marginal zone axodendritic complexes (Fig. 5). Further quantitative studies will be required to verify this impression and also to determine the relative frequencies of cortical boutons in the marginal zone and the deeper layers of subnucleus caudalis. In these experiments neither neurofilamentous nor electron-lucent types of degeneration have been seen, and interpretations have therefore relied upon the occurrence of electron-dense terminal knobs. Such dense knobs have been reported to occur in apparently normal central nervous system tissue 3. However, in our experiments, electron-dense axon terminals have not been encountered in those animals studied 30 h or 3 days following cortical ablation (animal s RD 96 and 131). It therefore seems likely that the dark profiles seen at 4-7 days survival do represent degenerating cortical terminals in the marginal zone of caudalis. While early forms of electron-dense degeneration may in fact occur at shorter survival times, the presence of axons and terminals with slightly gray axoplasm in the marginal zone of normal animals (see Figs. 8 and 9 in ref. 17) precludes reliable interpretation of earlier post-lesion changes. In addition, since electron-dense degeneration in these experiments has been most marked at survival times of 4-5 days, longer latency (12-14 day) transganglionic degeneration from operative injury to peripheral V fibers would seem to be an unlikely explanation for our observations. On the contrary, the dense knobs described by Gobel in the main sensory V nucleus following extensive bilateral cortical ablations 7 are virtually identical in size and synaptic relationships to the dark boutons encountered in the marginal zone in this investigation. Their earlier appearance in the main sensory V nucleus (2-4 days post-lesion in Gobel's series) possibly reflects the closer proximity of the main sensory nucleus to the cortical lesion sites. We are unaware of previous reports of cortical projections to the marginal zone
175 of the spinal dorsal horn or spinal V caudalis. Previous light microscopic investigations have indicated that the major sensorimotor cortical projection terminates in the magnocellular zone of the spinal V caudalis z2 while the sensorimotor cortical projection to the spinal dorsal horn has been described as terminating in Rexed's laminae IV to V114. Thus, cortical inhibitory and facilitatory effects on primary afferent sensory transmission have been assumed to be mediated by polysynaptic pathways possibly involving lamina IV neurons (see Fig. 4 in ref. 13). Our preliminary data indicate that some corticofugal axons may project directly to lamina I of the spinal V subnucleus caudalis. Since cells with electrophysiological characteristics of interneurons have recently been described in the marginal zone of caudalis 1°, even direct cortical input to the marginal zone may involve complex polysynaptic pathways. Further studies are required to clarify the anatomical substrates for the cortical modulatory effects on spinal V sensory transmission. This research was supported by N I H G r a n t NS 15622 and a TeacherInvestigator Development Award to R.C.D., Jr., NS 00589, awarded by the National Institute of Neurological and Communicative Disorders and Stroke, PHS. The authors gratefully acknowledge this support. We also appreciate the valuable technical assistance of Timothy Ross and the assistance of D o n n a Amsler and K a t h y Illyes in the preparation of the manuscript.
1 Basbaum, A. I. and Fields, H. L., Endogenous pain control mechanisms: review and hypothesis, Ann. Neurol., 4 (1978) 451--462. 2 Burton, H., Craig, A. D., Poulos, D. A. and Molt, J. T., Efferent projections from temperature sensitive recording loci within the marginal zone of the nucleus caudalis of the spinal trigeminal complex in the cat, J. comp. NeuroL, 183 (1979) 753-777. 3 Cohen, E. B. and Pappas, G. D., Dark profiles in the apparently-normal central nervous system: a problem in the electron microscopic identification of early anterograde axonal degeneration, J. comp. Neurol., 136 (1969) 375-396. 4 Coulter, J. D., Maunz, R. A. and Willis, W. D., Effects of stimulation of sensorimotor cortex on primate spinothalamic neurons, Brain Research, 65 (1974) 351-356. 5 Darian-Smith, I., Neural mechanisms of facial sensation, Int. Rev. Neurobiol., 9 (1966) 301-395. 6 Dunn, R. C. and Tolbert, D. L., The corticotrigeminal projection in the cat. A study of the organization of cortical projections to the spinal trigeminal nucleus, Brain Research, in press. 7 Gobel, S., Structural organization in the main sensory trigeminal nucleus. In R. Dubner and Y. Kawamura (Eds.), Oral-facial Sensory and Motor Mechanisms, Appleton-Century-Crofts, New York, 1971, pp. 183-202. 8 Gobel, S. and Hockfield, S., An anatomical analysis of the synaptic circuitry of layers I, II and III of the trigeminal nucleus caudalis in the cat. In D. J. Anderson and B. Matthews (Eds.), Pain in the Trigeminal Region, Elsevier/North-Holland, Amsterdam, 1977, pp. 203-211. 9 H6kfelt, T., Ljungdahl, A., Terenius, L., Elde, R. and Nilsson, G., Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P, Proc. nat. Acad. Sci. U.S.A., 74 (1977) 3081-3085. 10 Hubbard, J. I. and Hellon, R. F., Excitation and inhibition of marginal layer and interstitial interneurons in cat nucleus caudalis by mechanical stimuli, J. comp. Neurol., 193 (1980) 995-1007. 11 Kerr, F. W. L., The fine structure of the subnucleus caudalis of the trigeminal nerve, Brain Research, 23 (1970) 129-145. 12 Kerr, F. W. L., The organization of primary afferents in the subnucleus caudalis of the trigeminal: a light and electron microscopic study, Brain Research, 23 (1970) 147-165.
176 13 Kerr, F. W. L., Segmental circuitry and ascending pathways of the nociceptive system. In R. F. Beers Jr. and E. G. Bassett (Eds.), Mechanisms of Pain and Analgesic Compounds, Raven Press, New York, 1979, pp. 113-141. 14 Nyberg-Hansen, R., Sites of termination of corticospinal fibers in the cat. An experimental study with silver impregnation methods, J. comp. Neurol., 120 (1963) 369-391. 15 Poulos, D. A. and Molt, J. T., Thermosensory mechanisms in the spinal trigeminal nucleus of cats. In D. J. Anderson and B. M. Matthews (Eds.), Pain in the Trigeminal Region, Elsevier/NorthHolland, Amsterdam, 1977, pp. 443453. 16 Price, D. D., Dubner, R. and Hu, J. W., Trigeminothalamic neurons in nucleus caudalis responsive to tactile thermal and nociceptive stimulation of the monkey's face, J. Neurophysiol., 39 (1976) 936-953. 17 Ralston, H. J., I11, The fine structure of laminae I, II and llI of the macaque spinal cord, J. comp. Neurol., 184 (1979) 619 642. 18 Rexed, B., The cytoarchitectonic organization of the spinal cord in the cat, J. comp. Neurol., 296 (1952) 416-496. 19 Sessle, B. J., Hu, J. W., Dubner, R. and Lucier, G. E., Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). 1I. Modulation of responses to noxious and non-noxious stimuli by periaqueductal gray, nucleus raphe magnus, cerebral cortex, and afferent influences, and effect of naloxone, J. Neurophysiol., 45 (1981) 193-207. 20 Sotelo, C. and Palay, S. L., The fine structure of the lateral vestibular nucleus in the rat. 1. Neurons and neuroglial cells, J. Cell Biol., 36 (1968) 151-179. 21 Westrum, L. E. and Canfield, R. C., Light and electron microscopy of degeneration in the brain stem trigeminal nucleus following tooth pulp removal in adult cats. In D. J. Anderson and B. Matthews (Eds.), Pain in the Trigeminal Region, Elsevier/North-Holland, Amsterdam, 1977, pp. 171-179. 22 Wold, J. E. and Brodal, A., The projection of cortical sensorimotor regions onto the trigeminal nucleus in the cat. An experimental anatomical study, Neurobiology, 3 (1973) 353-375. 23 Woolsey, C. N., Patterns of sensory representation in the cerebral cortex. In H. F. Harlow and C. N. Woolsey (Eds.), Biological and Biochemical Bases of Behavior, Univ. Wisconsin Press, Madison, 1958, pp. 63 81.
171
Sensorimotor cortical projections to the marginal zone of the trigeminal subnucleus caudalis
ROBERT C. DUNN, Jr.* and KOK LEONG CHONG Division of Neurosurgery and Department of Anatomy, St. Louis University School of Medicine, St. Louis, MO 63104 (U.S.A.)
(Accepted October 15th, 1981) Key words: spinal trigeminal nucleus - - spinal trigeminal subnucleus caudalis - - electron microscopy pain pathways - - endogenous analgesia systems - - corticobulbar pathways -
-
An ultrastructural investigation of the marginal zone (lamina I) of the spinal trigeminal subnucleus caudalis was carried out in 7 adult cats at 30 h through 7 days after ablations of face area of the contralaterai sensorimotor cortex. Corticofugal boutons were observed to undergo electrondense degeneration in the marginal zone beginning 4 days after the cortical lesion. These boutons were small (1-2 #m), widely dispersed and made synaptic contacts onto small dendrites or dendritic spines. These new observations indicate that cortical inhibition and facilitation of ascending orofacial sensation may be mediated in part by a direct pathway to the marginal zone. There has been renewed interest in neuroanatomic substrates for pain transmission and modulation, particularly the descending endogenous analgesia systems projecting f r o m the brain stem (e.g. from the periaqueductal gray and the nucleus raphe magnus1,9). In contrast, the neuroanatomic organization of the descending pathways from the somatosensory cortex, also known to be effective in modifying transmission of noxious and non-noxious sensory information 4,5,19, has received less attention recently. To clarify the topography of the corticotrigeminal pathway in adult cats for ongoing developmental and plasticity studies, we have completed a light microscopic investigation of the projection from the coronal gyrus (face area of primary somatosensory cortex 23) to the spinal trigeminal (V) nucleus 6. Observations in this study suggested a cortical projection to the marginal zone of the spinal V subnucleus caudalis. Marginal zone neurons in the spinal V caudalis have been shown to respond specifically to noxious and non-noxious stimuli 15,1~ and these cells are also known to project to the thalamus2, a. Therefore, a cortical projection to the marginal zone would represent a potential anatomical substrate for the cortical modulation of ascending orofacial sensation. Furthermore, information about the synaptology of cortical afferents within the marginal zone would be expected to increase the understanding of mechanisms underlying such cortical effects. We report here the prelimi* Address for correspondence: Department of Anatomy, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, U.S.A. 0006-8993/82/0000-0000/$02.75 © Elsevier Biomedical Press
72
173 nary results of an ultrastructural study of the corticotrigeminal projection to the spinal V subnucleus caudalis. The findings suggest that the face area of primary sensorimotor cortex does project to the marginal zone of subnucleus caudalis in the cat. Seven healthy adult cats with normal dentition were used for this investigation. After anesthetization with ketamine hydrochloride (33 mg/kg i.m.), these animals underwent frontal craniectomy to expose the left coronal gyrus. Coronal cortex ablations were then made with electrocautery followed by aspiration. Lesions were carefully restricted to the coronal gyrus and were limited in depth to minimize inadvertent damage to underlying white matter pathways from other gyri. Following survival periods of from 30 h to 7 days (chosen to minimize likelihood of central V transganglionic degeneration 21 - - see below) the experimental animals were reanesthetized with an overdose of ketamine and underwent perfusion with 1 ~ paraformaldehyde, 1.5 ~o glutaraldehyde in a 0.15 M sodium diphosphate buffer. Transverse tissue sections from the brain stem were then processed for electron microscopy according to the methods of Sotelo and Palay z0. Sections from subnucleus caudalis contralateral to the cortical lesions were examined in J O E L 100 CX electron microscope. The electron microscopic studies of the marginal zone by Kerr 11,12, Gobel and Hockfield s and, most recently, the detailed quantitative studies by Ralston 17, have documented the ultrastructural features which characterize the marginal zone (lamina 1 of Rexed18). These major identifying characteristics include: (1) a band of neuropil 40-150 # m in width exhibiting an abundance of small terminals, most of which contain round vesicles, some with dense cores; (2) a fine meshwork of small myelinated axons; and (3) two neuronal types: one small (10-15/tm), the other large (20-30 #m) marginal cells of Waldeyer irregularly scattered throughout lamina I. In this study electron-dense corticotrigeminal terminals became apparent in the marginal zone of subnucleus caudalis four days following contralateral coronal gyrus
Fig. 1. Low power electron photomicrograph from marginal zone of subnucleus caudalis 5 days following contralateral coronal gyrus ablation. Two axon terminals undergoing dense degeneration (DTs) are indicated by arrows. These are immediately adjacent to the spinal trigeminal tract (STT). Fig. 2 illustrates another section through terminal on left at greater magnification. Scale bar equals 5 /~m. Animal RD 97. Fig. 2. Terminal undergoing electron-dense degeneration (DT) in the marginal zone of subnucleus caudalis. Higher magnification of another section through terminal on left in Fig. 1. Alterations in synaptic vesicles (V) are evident. Two asymmetric synaptic contacts onto a small dendrite (arrowheads) are present. Scale bar equals 0.5/~m. Animal RD 97. Fig. 3. Degenerating bouton from the marginal zone 5 days following contralateral coronal gyrus ablation. Marked irregularity of the contours of the bouton and alteration in vesicle shape and size (V) is evident. Arrowheads indicate asymmetric synapse onto a small dendritic profile. An adjacent profile containing pleomorphic vesicles may be making synaptic contact onto degenerating cortical bouton (*). Scale bar equals 0.5 #m. Animal RD 169. Fig. 4. An electron-dense cortical bouton with altered vesicles (V) displays highly scalloped outlines which extend between adjacent profiles. Five-day survival. Scale bar equals 0.5/~m. Animal RD 97. Fig. 5. An electron-dense degenerating terminal (DT) from the nucleus proprius. Arrowheads indicate asymmetric synaptic contacts onto primary dendrite (D). Five-day survival. Scale bar equals 1/~m. Animal RD 169.
174 ablation (animals RD 156 and 165). These cortical boutons were found widely dispersed throughout the width of the marginal zone from areas immediately adjacent to the spinal V tract (Fig. 1) to the outermost portions of the underlying substantia gelatinosa. These dark endings were few in number but, when encountered, tended to occur in small clusters of two or three. To date, only electron-dense degeneration has been observed and this became most marked five days after injury (RD 97 and 169). Figs. 1-4 illustrate typical examples of degenerating cortical boutons in the marginal zone of two animals (RD 97 and 169) which had undergone contralateral cortical ablation 5 days prior to sacrifice. As shown, the darkened terminals in the marginal zone were typically small (1-2/zm) and contained round, clear vesicles; occasional degenerating profiles also included a few dense core vesicles. These distorted boutons made synaptic contact with small (1-2/zm) dendrites or dendritic spines (Figs. 2 and 3). As yet, cortical boutons have not been seen making axosomatic contact with marginal neurons, nor have they been found as the presynaptic profile in axoaxonic arrangements. By 7 days after cortical ablation, fewer degenerating boutons were seen but darkened, thinly myelinated axons were readily found from 4 through 7 days survival in the marginal zone and its extensions into the spinal V tract. Occasional degenerating cortical terminals have been observed in the nucleus proprius (magnocellular nucleus) of caudalis. Here electron-dense terminals appeared to synapse onto dendrites of a distinctly larger size than those seen in the marginal zone axodendritic complexes (Fig. 5). Further quantitative studies will be required to verify this impression and also to determine the relative frequencies of cortical boutons in the marginal zone and the deeper layers of subnucleus caudalis. In these experiments neither neurofilamentous nor electron-lucent types of degeneration have been seen, and interpretations have therefore relied upon the occurrence of electron-dense terminal knobs. Such dense knobs have been reported to occur in apparently normal central nervous system tissue 3. However, in our experiments, electron-dense axon terminals have not been encountered in those animals studied 30 h or 3 days following cortical ablation (animal s RD 96 and 131). It therefore seems likely that the dark profiles seen at 4-7 days survival do represent degenerating cortical terminals in the marginal zone of caudalis. While early forms of electron-dense degeneration may in fact occur at shorter survival times, the presence of axons and terminals with slightly gray axoplasm in the marginal zone of normal animals (see Figs. 8 and 9 in ref. 17) precludes reliable interpretation of earlier post-lesion changes. In addition, since electron-dense degeneration in these experiments has been most marked at survival times of 4-5 days, longer latency (12-14 day) transganglionic degeneration from operative injury to peripheral V fibers would seem to be an unlikely explanation for our observations. On the contrary, the dense knobs described by Gobel in the main sensory V nucleus following extensive bilateral cortical ablations 7 are virtually identical in size and synaptic relationships to the dark boutons encountered in the marginal zone in this investigation. Their earlier appearance in the main sensory V nucleus (2-4 days post-lesion in Gobel's series) possibly reflects the closer proximity of the main sensory nucleus to the cortical lesion sites. We are unaware of previous reports of cortical projections to the marginal zone
175 of the spinal dorsal horn or spinal V caudalis. Previous light microscopic investigations have indicated that the major sensorimotor cortical projection terminates in the magnocellular zone of the spinal V caudalis z2 while the sensorimotor cortical projection to the spinal dorsal horn has been described as terminating in Rexed's laminae IV to V114. Thus, cortical inhibitory and facilitatory effects on primary afferent sensory transmission have been assumed to be mediated by polysynaptic pathways possibly involving lamina IV neurons (see Fig. 4 in ref. 13). Our preliminary data indicate that some corticofugal axons may project directly to lamina I of the spinal V subnucleus caudalis. Since cells with electrophysiological characteristics of interneurons have recently been described in the marginal zone of caudalis 1°, even direct cortical input to the marginal zone may involve complex polysynaptic pathways. Further studies are required to clarify the anatomical substrates for the cortical modulatory effects on spinal V sensory transmission. This research was supported by N I H G r a n t NS 15622 and a TeacherInvestigator Development Award to R.C.D., Jr., NS 00589, awarded by the National Institute of Neurological and Communicative Disorders and Stroke, PHS. The authors gratefully acknowledge this support. We also appreciate the valuable technical assistance of Timothy Ross and the assistance of D o n n a Amsler and K a t h y Illyes in the preparation of the manuscript.
1 Basbaum, A. I. and Fields, H. L., Endogenous pain control mechanisms: review and hypothesis, Ann. Neurol., 4 (1978) 451--462. 2 Burton, H., Craig, A. D., Poulos, D. A. and Molt, J. T., Efferent projections from temperature sensitive recording loci within the marginal zone of the nucleus caudalis of the spinal trigeminal complex in the cat, J. comp. NeuroL, 183 (1979) 753-777. 3 Cohen, E. B. and Pappas, G. D., Dark profiles in the apparently-normal central nervous system: a problem in the electron microscopic identification of early anterograde axonal degeneration, J. comp. Neurol., 136 (1969) 375-396. 4 Coulter, J. D., Maunz, R. A. and Willis, W. D., Effects of stimulation of sensorimotor cortex on primate spinothalamic neurons, Brain Research, 65 (1974) 351-356. 5 Darian-Smith, I., Neural mechanisms of facial sensation, Int. Rev. Neurobiol., 9 (1966) 301-395. 6 Dunn, R. C. and Tolbert, D. L., The corticotrigeminal projection in the cat. A study of the organization of cortical projections to the spinal trigeminal nucleus, Brain Research, in press. 7 Gobel, S., Structural organization in the main sensory trigeminal nucleus. In R. Dubner and Y. Kawamura (Eds.), Oral-facial Sensory and Motor Mechanisms, Appleton-Century-Crofts, New York, 1971, pp. 183-202. 8 Gobel, S. and Hockfield, S., An anatomical analysis of the synaptic circuitry of layers I, II and III of the trigeminal nucleus caudalis in the cat. In D. J. Anderson and B. Matthews (Eds.), Pain in the Trigeminal Region, Elsevier/North-Holland, Amsterdam, 1977, pp. 203-211. 9 H6kfelt, T., Ljungdahl, A., Terenius, L., Elde, R. and Nilsson, G., Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P, Proc. nat. Acad. Sci. U.S.A., 74 (1977) 3081-3085. 10 Hubbard, J. I. and Hellon, R. F., Excitation and inhibition of marginal layer and interstitial interneurons in cat nucleus caudalis by mechanical stimuli, J. comp. Neurol., 193 (1980) 995-1007. 11 Kerr, F. W. L., The fine structure of the subnucleus caudalis of the trigeminal nerve, Brain Research, 23 (1970) 129-145. 12 Kerr, F. W. L., The organization of primary afferents in the subnucleus caudalis of the trigeminal: a light and electron microscopic study, Brain Research, 23 (1970) 147-165.
176 13 Kerr, F. W. L., Segmental circuitry and ascending pathways of the nociceptive system. In R. F. Beers Jr. and E. G. Bassett (Eds.), Mechanisms of Pain and Analgesic Compounds, Raven Press, New York, 1979, pp. 113-141. 14 Nyberg-Hansen, R., Sites of termination of corticospinal fibers in the cat. An experimental study with silver impregnation methods, J. comp. Neurol., 120 (1963) 369-391. 15 Poulos, D. A. and Molt, J. T., Thermosensory mechanisms in the spinal trigeminal nucleus of cats. In D. J. Anderson and B. M. Matthews (Eds.), Pain in the Trigeminal Region, Elsevier/NorthHolland, Amsterdam, 1977, pp. 443453. 16 Price, D. D., Dubner, R. and Hu, J. W., Trigeminothalamic neurons in nucleus caudalis responsive to tactile thermal and nociceptive stimulation of the monkey's face, J. Neurophysiol., 39 (1976) 936-953. 17 Ralston, H. J., I11, The fine structure of laminae I, II and llI of the macaque spinal cord, J. comp. Neurol., 184 (1979) 619 642. 18 Rexed, B., The cytoarchitectonic organization of the spinal cord in the cat, J. comp. Neurol., 296 (1952) 416-496. 19 Sessle, B. J., Hu, J. W., Dubner, R. and Lucier, G. E., Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). 1I. Modulation of responses to noxious and non-noxious stimuli by periaqueductal gray, nucleus raphe magnus, cerebral cortex, and afferent influences, and effect of naloxone, J. Neurophysiol., 45 (1981) 193-207. 20 Sotelo, C. and Palay, S. L., The fine structure of the lateral vestibular nucleus in the rat. 1. Neurons and neuroglial cells, J. Cell Biol., 36 (1968) 151-179. 21 Westrum, L. E. and Canfield, R. C., Light and electron microscopy of degeneration in the brain stem trigeminal nucleus following tooth pulp removal in adult cats. In D. J. Anderson and B. Matthews (Eds.), Pain in the Trigeminal Region, Elsevier/North-Holland, Amsterdam, 1977, pp. 171-179. 22 Wold, J. E. and Brodal, A., The projection of cortical sensorimotor regions onto the trigeminal nucleus in the cat. An experimental anatomical study, Neurobiology, 3 (1973) 353-375. 23 Woolsey, C. N., Patterns of sensory representation in the cerebral cortex. In H. F. Harlow and C. N. Woolsey (Eds.), Biological and Biochemical Bases of Behavior, Univ. Wisconsin Press, Madison, 1958, pp. 63 81.