Brain Research, 177 (1979) 379-383 © Elsevier/North-Holland Biomedical Press
379
Functional changes in cat somatic sensory-motor cortex during short-term reversible epidural blocks
JACQUELINE METZLER and PHILIP S. MARKS Department o f Surgery, Section of Neurological Surgery, Yale University School of Medicine, New Haven, Conn. 06510 (U.S.A.} (Accepted July 26th, 1979)
Spatial representations of auditory, visual and somatic stimuli on their receptor surfaces are preserved as the information ascends the afferent pathways to the cortex. In the somatosensory system, the body surface projection provides a convenient substrate for investigating functional plasticity and the effects of injury to the spinal cord and peripheral nerves. The forearm representation in the kitten sensory-motor cortex (SmI) 16, for example, increased in size following discriminative training in which the contralateral forearm was stimulatedlz. Similarly, after selective hindlimb deafferentation in adult cats, the representation of the remaining intact afferents increased in the spinal cord1, 3 and dorsal column nucleia,l°, extending into the area previously representing the hindlimb. Such functional changes have also been observed in the thalamus and cortex of the ratlL Here we describe modifications in the topographical projection in SmI of adult cats during reversible epidural blocks of the L4-L5 dorsal roots. This procedure permits the uninterrupted study of the response characteristics of individual cortical units before, during and after the afferent blocks. The data presented here were obtained from 4 short-haired, adult cats in 14 recording sessions over a 3 month period. Initially, a chronic recording chamber (see Fig. 1A), enclosing a region 12 mm in diameter, was implanted over the left postcruciate cortex under halothane (Fluothane) anesthesia, and at least one week was allowed to elapse before recordings began. During each recording session, the animals were paralyzed with gallamine triethiodide (Flaxedil) (4.0 mg/kg/h, IV), artificially respired with 65 ~o N20/35 ~o 02, and positioned in a stereotaxic apparatus. Core temperature, heart rate and pCO2 were monitored continuously and maintained within normal limits. Pressure points were infused periodically with 3 ~o Lidocaine HCI. Single-unit activity was recorded extracellularly with vinyl-insulated tungsten microelectrodes5 having tip diameters < 1/~m. Electrode penetrations were perpendicular to the cortical surface and separated by 300-500 #m. The body surface projection on SmI was carefully determined for each of the 4 animals; thus, each cat served as its own control for the subsequent epidural blocks of the L4-L5 dorsal roots. The somatopic representations and the general response properties of the 213 control units sampled were similar for all 4 cats and in agreement with earlier
380
A
Cylindrical plug with clear top
Dental o c r y l i c ~
S k i n ~ Frontal sinus" - ' - ~ Acry,ic dam~., Bone~ ' ~ D ~
~
Chamber base CORTEX
~ra
B
1
2
Fig. 1. A: cross-section of the recording chamber. B: examples of receptive fields (RFs) before, during and after the L4-L5 epidural blocks. Enclosed regions represent the pre- and post-block RFs, striped areas the RFs during the blocks (see text for details). The location of the recording chamber and the electrode penetrations in Sml in which each of the units was found is shown in the center. CRU, cruciate sulcus; ANS, ansate sulcus; COR, coronal sulcus; D, post-cruciate dimple. findings8,11,12,16. Sixty-eight per cent of these units responded to hair m o v e m e n t or light mechanical d e f o r m a t i o n of the skin a n d were classifed as ' c u t a n e o u s ' , while 22 ~ responded to j o i n t m o v e m e n t or pressure o n the periosteum a n d fascia a n d were
381 termed 'deep'. The remaining 10 % were spontaneously active but not influenced by mechanical stimulation, (see Table I). All responsive units were driven by stimulation of the contralateral body surface; no ipsilateral representation was found. Most excitable units were located in the middle cortical layers and exhibited static 'lemniscal' properties such as modality and topographical specificity 11. Excitatory receptive fields (RFs) were stable in both location and size, never stocking-like and generally small, sometimes only 9 sq. mm on the distal fore- and hindlimbs. Prior to establishing the epidural blocks, units were isolated 750-1350 #m below the cortical surface in the region of SmI known to receive afferent projections from the contralateral upper hindlimb. The response and RF properties of each selected cell were carefully monitored until it was certain that a stable recording situation existed. The L4-L5 dorsal roots which innervate the upper hindlimb 7 were then temporally blocked by epidural anesthesia (0.25 ~o bupivacaine HC1 with epinephrine 1:200,000), using standard lumbar puncture techniques. During the onset of the block, decreasing numbers of spike discharges were observed in the bursts following stimulation of the
TABLE I
Classification of units in S m l by submodality Control Pre-
During epidural block
and postblock
Hair
Light
Mixed* Deep
Joint touch or movepressure ment
touch or
pressure
CutanUnreeous and sponsdeep ire
mixed Hair
Cutaneous
Light touch or pressure Mixed* Subtotal
Deep
85 (40%)
17 (3770)
43 (20%) 17 (8 70) 145 (68%)
10 (2270) 3 (7 % ) 30 (65%)
i Deep touch or 32 pressure ( 1 5 % ) Joint 15 I movement (7 7000) Subtotal
Unresponsive
47 (22%) 21 (1070)
10 (22%) 2 (47o) 12 (26%) 4 (9%)
3 (7%)
--
--
3 (7%)
-3 (7%)
-3 (7%)
-1 (2 %) 1 (2%)
--
--
--
.
.
.
-.
--
--
1 (2%)
1 (2%)
--
--
---
-1 (2%)
-1 (270) 1 (2%)
--
-3 (7%)
8 (17%)
.
-.
2 (4%)
8 (17%)
-.
.
.
.
---
11 (24%) 6 (13%) 2 (4 70) 19 (41%)
2 (4%) 1 (2%) 3 (7%) 4 (9%)
* Includes units activated by cutaneous stimuli whose submodality specificity was not completely defined.
382 previously defined RF of the cell. Within 10-15 min.~ responses to stimulation of the pre-block RF began to fail, at which time a re-examination of the entire body surface was initiated. To date, 46 units have been studied while the blocks were in effect, 21 of these for periods of 2-4 h each, after which the pre-block RF was again effective in driving the cell. Twenty-six (56.5 ~ ) of these units failed to respond to any mechanical peripheral stimulation during the blocks. Most of these units responded to cutaneous stimuli before and after the blocks. Five cells (10.9 ~o) had pre-block RFs which included the posterior region of the abdomen as well as the upper leg; only the leg portion of the RF disappeared while the block was in effect, and reappeared as the anesthetic wore off (see Fig. 1B1). Similarly, 2 units (4.3~) with pre-block RFs encompassing the posterior part of the upper leg and the proximal tail region lost the former portion of the field during the block (see Fig. 1B~). The normal excitatory RFs of the remaining 13 cells (28.3 ~ ) were located on the hindlimb, proximal to the knee. As the roots were blocked, new RFs appeared on the foot or toes ( n ~ 5 ; see Fig. 1Ba), or on the abdomen (n=7). One unit unequivocally had a dual RF, with separate excitatory fields on the toes and upper abdomen (see Fig. 1B4). Cells with widely separated, double RFs have also been found in the spinal cord 1, the gracile nucleus3,1° and SmI 4 of the chronically deafferented cat. These new RFs persisted throughout the duration of the blocks (2-4 h). Mechanical stimulation of the regions where these new fields were located was not effective in influencing the units before or after the blocks. The response properties of the cells that began responding to new regions of the body during the blocks differed from the pre-block characteristics in several ways: (i) the responses frequently habituated to repetitive ( > 1/sec) stimulation. Analogous findings have been reported 3,1° in the gracile nucleus following deafferentation; (ii) modality specificity was not always preserved; i.e. units initially classified as 'cutaneous' sometime became 'deep' during the block, requiring strong mechanical stimuli to drive them. Table I presents the effects of the epidural blocks on the modality subgroups. The appearance of more units with higher thresholds of stimulation has also been reported in the gracile nucleus after deafferentation3,1°, and in SmI following selective dorsal-root rhizotomies 4 and spinal tractotomies 9; and (iii) RF sizes were not as uniform; e.g. RFs on the foot varied from extremely small (4 sq. mm) to stockinglike. The RFs and response characteristics of 53 units examined after the blocks were normal in all respects. Moreover, post-recording examinations revealed no neurological deficits. The immediacy and reversibility of the effects reported here indicate that sprouting of intact afferents or other growth processes are not responsible. Since response latencies were not recorded, we cannot exclude the use of polysynaptic pathways which may have been inhibited by the normal inputs, although there is evidence for monosynaptic connections in the spinal cord 1 and gracile nucleus3,1° following selective deafferentation. Our results, like those of Wall 14 and colleagues, suggest that widespread afferent connections are present in the intact animal but that only some of these afferents are functionally effective. Upon removal of these dominant
383
specific inputs, the widespread connections become more apparent. Comparable immediate unmasking of non-functional pathways has also been reported in the visual system, involving the reversal of the effects of monocular deprivation in catsZ,6. These immediate effects do not imply that other mechanisms cannot also operate, particularly in the chronic state, but that modifications in synaptic connectivity are not always a prerequisite for functional plasticity. A change in the available inputs may be sufficient. This research was supported by NIH Grant 2 P50 NS10174-07. We thank H. Henik and J. Silvestri for excellent technical assistance, M. Pond for assisting us with the epidural blocks, F. Cappiello for designing and constructing the epidural catheters, J. Frank for comments on the manuscript and W. F. Collins for his continuing support.
1 Basbaum, A. I. and Wall, P. D., Chronic changes in the response of cells in adult cat dorsal horn following partial deafferentation: the appearance of responding cells in a previously non-responsive region, Brain Research, 116 (1976) 181-204. 2 Berman, N. and Sterling, P., Cortical suppression of the retino-collicular pathway in the monocularly deprived cat, J. Physiol. (Lond.), 255 (1976) 263-273. 3 Dostrovsky, J. O., Millar, J. and Wall, P. D., The immediate shift of afferent drive of dorsal column nucleus cells following deafferentation: a comparison of acute and chronic deafferentation in gracile nucleus and spinal cord, Exp. Neurol., 52 (1976) 480-495. 4 Franck, J. I., On the Functional Reorganization of Cat Somatic Sensory-Motor Cortex (Sml) via Selective Dorsal-Root Rhizotomies, Yale University School of Medicine, M.D. Thesis, 1979. 5 Hubel, D. H., Tungsten microelectrodes for recording from single units, Science, 125 (1957) 549-550. 6 Kratz, K. E., Spear, P. D. and Smith, D. C., Post-critical period reversal of effects of monocular deprivation on striate cortex cells in the cat, J. NeurophysioL, 39 (1976) 501-511. 7 Kuhn, R. A., Organization of tactile dermatomes in cat and monkey, J. Neurophysiol., 16 (1953) 169-182. 8 Levitt, J. and Levitt, M., Sensory hind-limb representation in SmI cortex of the cat. A unit analysis, Exp. Neurol., 22 (1968) 259-275. 9 Levitt, M. and Levitt, J., Sensory hind-limb representation in SmI cortex of the cat after spinal tractotomies, Exp. Neurol., 22 (1968) 276--302. 10 Millar, J., Basbaum, A. I. and Wall, P. D., Restructuring of the somatotopic map and appearance of abnormal neuronal activity in the gracile nucleus after partial deafferentation, Exp. NeuroL, 50 (1976) 658-672. 11 Mountcastle, V. B., Modality and topographic properties of single neurons of cat's somatic sensory cortex, J. Neurophysiol., 20 (1957) 408-434. 12 Mountcastle, V. B., Some functional properties of the somatic afferent system. In W. A. Rosenblith (Ed.), Sensory Communication, MIT Press, Cambridge, 1961, pp. 403-436. 13 Spinelli, D. N., Metzler, J. and Phelps, R. W., Neural correlates of visual experience in single units of cat's visual and somatosensory cortex, Neurosci. Abstr., 5 (1975) 137. 14 Wall, P. D., The presence of ineffective synapses and the circumstances that unmask them, Phil. Trans. B, 278 (1977) 361-372. 15 Wall, P. D. and Egger, M. D., Formation of new connexions in adult rat brains after partial deafferentation, Nature (Lond.), 232 (1971) 542-545. 16 Woolsey, C. N., Organization of somatic sensory and motor areas of the cerebral cortex. In H. F. Harlow and C. N. Woolsey (Eds.), Biological and Biochemical Bases of Behavior, University of Wisconsin Press, Madison, 1958, p. 76.
379
Functional changes in cat somatic sensory-motor cortex during short-term reversible epidural blocks
JACQUELINE METZLER and PHILIP S. MARKS Department o f Surgery, Section of Neurological Surgery, Yale University School of Medicine, New Haven, Conn. 06510 (U.S.A.} (Accepted July 26th, 1979)
Spatial representations of auditory, visual and somatic stimuli on their receptor surfaces are preserved as the information ascends the afferent pathways to the cortex. In the somatosensory system, the body surface projection provides a convenient substrate for investigating functional plasticity and the effects of injury to the spinal cord and peripheral nerves. The forearm representation in the kitten sensory-motor cortex (SmI) 16, for example, increased in size following discriminative training in which the contralateral forearm was stimulatedlz. Similarly, after selective hindlimb deafferentation in adult cats, the representation of the remaining intact afferents increased in the spinal cord1, 3 and dorsal column nucleia,l°, extending into the area previously representing the hindlimb. Such functional changes have also been observed in the thalamus and cortex of the ratlL Here we describe modifications in the topographical projection in SmI of adult cats during reversible epidural blocks of the L4-L5 dorsal roots. This procedure permits the uninterrupted study of the response characteristics of individual cortical units before, during and after the afferent blocks. The data presented here were obtained from 4 short-haired, adult cats in 14 recording sessions over a 3 month period. Initially, a chronic recording chamber (see Fig. 1A), enclosing a region 12 mm in diameter, was implanted over the left postcruciate cortex under halothane (Fluothane) anesthesia, and at least one week was allowed to elapse before recordings began. During each recording session, the animals were paralyzed with gallamine triethiodide (Flaxedil) (4.0 mg/kg/h, IV), artificially respired with 65 ~o N20/35 ~o 02, and positioned in a stereotaxic apparatus. Core temperature, heart rate and pCO2 were monitored continuously and maintained within normal limits. Pressure points were infused periodically with 3 ~o Lidocaine HCI. Single-unit activity was recorded extracellularly with vinyl-insulated tungsten microelectrodes5 having tip diameters < 1/~m. Electrode penetrations were perpendicular to the cortical surface and separated by 300-500 #m. The body surface projection on SmI was carefully determined for each of the 4 animals; thus, each cat served as its own control for the subsequent epidural blocks of the L4-L5 dorsal roots. The somatopic representations and the general response properties of the 213 control units sampled were similar for all 4 cats and in agreement with earlier
380
A
Cylindrical plug with clear top
Dental o c r y l i c ~
S k i n ~ Frontal sinus" - ' - ~ Acry,ic dam~., Bone~ ' ~ D ~
~
Chamber base CORTEX
~ra
B
1
2
Fig. 1. A: cross-section of the recording chamber. B: examples of receptive fields (RFs) before, during and after the L4-L5 epidural blocks. Enclosed regions represent the pre- and post-block RFs, striped areas the RFs during the blocks (see text for details). The location of the recording chamber and the electrode penetrations in Sml in which each of the units was found is shown in the center. CRU, cruciate sulcus; ANS, ansate sulcus; COR, coronal sulcus; D, post-cruciate dimple. findings8,11,12,16. Sixty-eight per cent of these units responded to hair m o v e m e n t or light mechanical d e f o r m a t i o n of the skin a n d were classifed as ' c u t a n e o u s ' , while 22 ~ responded to j o i n t m o v e m e n t or pressure o n the periosteum a n d fascia a n d were
381 termed 'deep'. The remaining 10 % were spontaneously active but not influenced by mechanical stimulation, (see Table I). All responsive units were driven by stimulation of the contralateral body surface; no ipsilateral representation was found. Most excitable units were located in the middle cortical layers and exhibited static 'lemniscal' properties such as modality and topographical specificity 11. Excitatory receptive fields (RFs) were stable in both location and size, never stocking-like and generally small, sometimes only 9 sq. mm on the distal fore- and hindlimbs. Prior to establishing the epidural blocks, units were isolated 750-1350 #m below the cortical surface in the region of SmI known to receive afferent projections from the contralateral upper hindlimb. The response and RF properties of each selected cell were carefully monitored until it was certain that a stable recording situation existed. The L4-L5 dorsal roots which innervate the upper hindlimb 7 were then temporally blocked by epidural anesthesia (0.25 ~o bupivacaine HC1 with epinephrine 1:200,000), using standard lumbar puncture techniques. During the onset of the block, decreasing numbers of spike discharges were observed in the bursts following stimulation of the
TABLE I
Classification of units in S m l by submodality Control Pre-
During epidural block
and postblock
Hair
Light
Mixed* Deep
Joint touch or movepressure ment
touch or
pressure
CutanUnreeous and sponsdeep ire
mixed Hair
Cutaneous
Light touch or pressure Mixed* Subtotal
Deep
85 (40%)
17 (3770)
43 (20%) 17 (8 70) 145 (68%)
10 (2270) 3 (7 % ) 30 (65%)
i Deep touch or 32 pressure ( 1 5 % ) Joint 15 I movement (7 7000) Subtotal
Unresponsive
47 (22%) 21 (1070)
10 (22%) 2 (47o) 12 (26%) 4 (9%)
3 (7%)
--
--
3 (7%)
-3 (7%)
-3 (7%)
-1 (2 %) 1 (2%)
--
--
--
.
.
.
-.
--
--
1 (2%)
1 (2%)
--
--
---
-1 (2%)
-1 (270) 1 (2%)
--
-3 (7%)
8 (17%)
.
-.
2 (4%)
8 (17%)
-.
.
.
.
---
11 (24%) 6 (13%) 2 (4 70) 19 (41%)
2 (4%) 1 (2%) 3 (7%) 4 (9%)
* Includes units activated by cutaneous stimuli whose submodality specificity was not completely defined.
382 previously defined RF of the cell. Within 10-15 min.~ responses to stimulation of the pre-block RF began to fail, at which time a re-examination of the entire body surface was initiated. To date, 46 units have been studied while the blocks were in effect, 21 of these for periods of 2-4 h each, after which the pre-block RF was again effective in driving the cell. Twenty-six (56.5 ~ ) of these units failed to respond to any mechanical peripheral stimulation during the blocks. Most of these units responded to cutaneous stimuli before and after the blocks. Five cells (10.9 ~o) had pre-block RFs which included the posterior region of the abdomen as well as the upper leg; only the leg portion of the RF disappeared while the block was in effect, and reappeared as the anesthetic wore off (see Fig. 1B1). Similarly, 2 units (4.3~) with pre-block RFs encompassing the posterior part of the upper leg and the proximal tail region lost the former portion of the field during the block (see Fig. 1B~). The normal excitatory RFs of the remaining 13 cells (28.3 ~ ) were located on the hindlimb, proximal to the knee. As the roots were blocked, new RFs appeared on the foot or toes ( n ~ 5 ; see Fig. 1Ba), or on the abdomen (n=7). One unit unequivocally had a dual RF, with separate excitatory fields on the toes and upper abdomen (see Fig. 1B4). Cells with widely separated, double RFs have also been found in the spinal cord 1, the gracile nucleus3,1° and SmI 4 of the chronically deafferented cat. These new RFs persisted throughout the duration of the blocks (2-4 h). Mechanical stimulation of the regions where these new fields were located was not effective in influencing the units before or after the blocks. The response properties of the cells that began responding to new regions of the body during the blocks differed from the pre-block characteristics in several ways: (i) the responses frequently habituated to repetitive ( > 1/sec) stimulation. Analogous findings have been reported 3,1° in the gracile nucleus following deafferentation; (ii) modality specificity was not always preserved; i.e. units initially classified as 'cutaneous' sometime became 'deep' during the block, requiring strong mechanical stimuli to drive them. Table I presents the effects of the epidural blocks on the modality subgroups. The appearance of more units with higher thresholds of stimulation has also been reported in the gracile nucleus after deafferentation3,1°, and in SmI following selective dorsal-root rhizotomies 4 and spinal tractotomies 9; and (iii) RF sizes were not as uniform; e.g. RFs on the foot varied from extremely small (4 sq. mm) to stockinglike. The RFs and response characteristics of 53 units examined after the blocks were normal in all respects. Moreover, post-recording examinations revealed no neurological deficits. The immediacy and reversibility of the effects reported here indicate that sprouting of intact afferents or other growth processes are not responsible. Since response latencies were not recorded, we cannot exclude the use of polysynaptic pathways which may have been inhibited by the normal inputs, although there is evidence for monosynaptic connections in the spinal cord 1 and gracile nucleus3,1° following selective deafferentation. Our results, like those of Wall 14 and colleagues, suggest that widespread afferent connections are present in the intact animal but that only some of these afferents are functionally effective. Upon removal of these dominant
383
specific inputs, the widespread connections become more apparent. Comparable immediate unmasking of non-functional pathways has also been reported in the visual system, involving the reversal of the effects of monocular deprivation in catsZ,6. These immediate effects do not imply that other mechanisms cannot also operate, particularly in the chronic state, but that modifications in synaptic connectivity are not always a prerequisite for functional plasticity. A change in the available inputs may be sufficient. This research was supported by NIH Grant 2 P50 NS10174-07. We thank H. Henik and J. Silvestri for excellent technical assistance, M. Pond for assisting us with the epidural blocks, F. Cappiello for designing and constructing the epidural catheters, J. Frank for comments on the manuscript and W. F. Collins for his continuing support.
1 Basbaum, A. I. and Wall, P. D., Chronic changes in the response of cells in adult cat dorsal horn following partial deafferentation: the appearance of responding cells in a previously non-responsive region, Brain Research, 116 (1976) 181-204. 2 Berman, N. and Sterling, P., Cortical suppression of the retino-collicular pathway in the monocularly deprived cat, J. Physiol. (Lond.), 255 (1976) 263-273. 3 Dostrovsky, J. O., Millar, J. and Wall, P. D., The immediate shift of afferent drive of dorsal column nucleus cells following deafferentation: a comparison of acute and chronic deafferentation in gracile nucleus and spinal cord, Exp. Neurol., 52 (1976) 480-495. 4 Franck, J. I., On the Functional Reorganization of Cat Somatic Sensory-Motor Cortex (Sml) via Selective Dorsal-Root Rhizotomies, Yale University School of Medicine, M.D. Thesis, 1979. 5 Hubel, D. H., Tungsten microelectrodes for recording from single units, Science, 125 (1957) 549-550. 6 Kratz, K. E., Spear, P. D. and Smith, D. C., Post-critical period reversal of effects of monocular deprivation on striate cortex cells in the cat, J. NeurophysioL, 39 (1976) 501-511. 7 Kuhn, R. A., Organization of tactile dermatomes in cat and monkey, J. Neurophysiol., 16 (1953) 169-182. 8 Levitt, J. and Levitt, M., Sensory hind-limb representation in SmI cortex of the cat. A unit analysis, Exp. Neurol., 22 (1968) 259-275. 9 Levitt, M. and Levitt, J., Sensory hind-limb representation in SmI cortex of the cat after spinal tractotomies, Exp. Neurol., 22 (1968) 276--302. 10 Millar, J., Basbaum, A. I. and Wall, P. D., Restructuring of the somatotopic map and appearance of abnormal neuronal activity in the gracile nucleus after partial deafferentation, Exp. NeuroL, 50 (1976) 658-672. 11 Mountcastle, V. B., Modality and topographic properties of single neurons of cat's somatic sensory cortex, J. Neurophysiol., 20 (1957) 408-434. 12 Mountcastle, V. B., Some functional properties of the somatic afferent system. In W. A. Rosenblith (Ed.), Sensory Communication, MIT Press, Cambridge, 1961, pp. 403-436. 13 Spinelli, D. N., Metzler, J. and Phelps, R. W., Neural correlates of visual experience in single units of cat's visual and somatosensory cortex, Neurosci. Abstr., 5 (1975) 137. 14 Wall, P. D., The presence of ineffective synapses and the circumstances that unmask them, Phil. Trans. B, 278 (1977) 361-372. 15 Wall, P. D. and Egger, M. D., Formation of new connexions in adult rat brains after partial deafferentation, Nature (Lond.), 232 (1971) 542-545. 16 Woolsey, C. N., Organization of somatic sensory and motor areas of the cerebral cortex. In H. F. Harlow and C. N. Woolsey (Eds.), Biological and Biochemical Bases of Behavior, University of Wisconsin Press, Madison, 1958, p. 76.
