Exp Brain Res (1992) 90:343-345
Experimental BrainResearch 9 Springer-Verlag1992
Constancy of motor axon conduction time during growth in rats Xiang Yang Chen, Jonathan S. Carp, and Jonathan R. Wolpaw Wadsworth Center for Laboratories and Research, New York State Department of Health and State University of New York, Albany, NY 12201~)509, USA Received December 5, 1991 / Accepted March 19, 1992
Summary. A x o n conduction distance, conduction velocity, and conduction time were measured for individual triceps surae m o t o n e u r o n s in Sprague-Dawley rats weighing 230-630 g (i.e., age range 6-16 weeks). Both conduction distance (nerve length) and velocity were closely correlated with weight (r = 0.95 and r = 0.82, respectively). In contrast, conduction time did not change as weight increased nearly threefold. This striking constancy is p r o b a b l y due to a corresponding increase in axon diameter. It could contribute to maintenance of stable m o t o r performance during rapid growth.
Key words: M o t o n e u r o n - M o t o r axon - N e r v e conduction - D e v e l o p m e n t - R a t
increase in m a x i m u m conduction velocity as measured by nerve volley. As a result, in spite of rapid change in body size, peripheral nerve conduction time remained the same, at least for the largest diameter axons assessed by the nerve volley measurement. In conjunction with efforts to define the physiologic and anatomic substrates of operantly conditioned plasticity in the spinal cord (Wolpaw and Carp 1990 for review; W o l p a w et al. 1991), we are studying triceps surae m o t o n e u r o n s in rat lumbar spinal cord. Initial studies suggested a strong correlation between animal age and axon conduction velocity. This study set out to document and define that relationship. The data indicate that a relation like that found in young kittens (Hursh 1939a, b) is present in rat over a considerable period of rapid growth.
Introduction Nerve conduction velocities change with age, especially during early life (Hursh 1939a, b; W a g m a n and Lesse 1952; Norris et al. 1953; Birren and Wall 1956; H o p k i n s and L a m b e r t 1973; Lafratta and Zalis 1973; D o r f m a n and Bosley 1979; Sato et al. 1985; Morales et al. 1987; K a n d a and Hashizume 1989; Wheeler 1990). In humans, m a x i m u m m o t o r and sensory nerve conduction velocities increase f r o m 33 m/s at one m o n t h of age to over 50 m/s at 4 years, remain stable through early and middle adulthood, and then begin to decrease at a b o u t age 50 (Knowlton and Britt 1949; W a g m a n and Lesse 1952; Wagner and Buchthal 1972; T r o j a b o r g 1976). C o m p a r a ble increases in early life and decreases with aging occur in the horse and in the rat (Wheeler 1990; Birren and Wall 1956; Sato et al. 1985; K a n d a and Hashizume 1989). The studies of H u r s h (1939a, b) are of particular interest. Unlike other studies which reveal only that conduction velocity tends to increase with growth particularly early in life, his studies found in kittens of 0 3 m o n t h s that the increase in leg length was exactly matched by an Correspondence to: X.Y. Chen, CNS Studies Section, Wadsworth Laboratories, P.O. Box 509, Albany, NY 12201-0509, USA
Material and methods Experiments were performed on 21 male Sprague-Dawley rats of 230-630 g (i.e., age range 6.16 weeks according to the supplier and our own observation). All animal procedures were in accord with DHEW Publ. No. (NIH) 85 23, "Guide for the Care and Use of Laboratory Animals," and had been reviewed and approved by the Institutional Animal Care and Use Committee of the Wadsworth Center. Surgical anaesthesia was induced with sodium pentobarbital (intraperitoneal, 60 mg/kg) and maintained with small additional doses (intraperitoneal, 15-20 mg/kg) at 30-60 min intervals throughout the 6-10 h course of the experiment. The trachea was cannulated. A T13 L1 laminectomy and longitudinal incision of the dura exposed the lumbar enlargement of the spinal cord (L3-L6). The animal was then positioned securely in a stereotaxic frame with ear bars, two vertebral clamps (one rostral to the laminectomy and one caudal) and a tail clamp. The animal was artificially ventilated and a bilateral pneumothorax was performed to provide the stability needed for intracellular recording. The tibial nerve of one side was exposed and the branches innervating the triceps surae (TS) muscles (medial gastrocnemius, lateral gastrocnemius and soleus) were cut as close to the main nerve as possible. The exposed tibial nerve was placed on two bipolar stimulating electrode pairs. One bipolar electrode pair was just proximal to the cut TS branches and the other was about 1 cm distal to these branches. Warmed mineral oil covered both the spinal cord and the exposed nerve. Heart rate
344 and expired pCO2 were monitored and maintained within normal physiological limits. Body temperature was kept at 37-38 ~ C and the temperatures of the oil pools were kept at 36-37 ~ C. At the end of the study, the anesthetized animal was euthanized with an overdose of pentobarbital. Intracellular recordings were obtained with glass mieroelectrodes (tip diam. about 2 ~m) filled with either 3 M KC1 solution (initial resistance 4-10 M~) or 6-8% horseradish peroxidase (HRP, Sigma type VI) in 0.5 M KCl-tris buffer (initial resistance 20-50 M~). The microelectrode began at the dorsal surface of the spinal cord and was advanced by a stepping microdrive in steps of 5 ~tm in order to impale motoneurons. During electrode advance, the proximal tibial nerve electrode pair delivered 1-Hz square pulses (0.05-ms duration) at an intensity three times the threshold for production of a volley at the cord dorsum. Intracellular recording and current injection were performed with a high impedance amplifier. Motoneurons were identified by their antidromic response to peripheral nerve stimulation. The antidromic nature of the action potential was confirmed by its origin from a fiat membrane potential (i.e., without a preceding synaptic potential) and its ability to follow high frequency stimulation (i.e., > 50-Hz) without latency shift. Motoneurons that were antidromically activated by the proximal bipolar electrode pair but not by the distal bipolar electrode pair were assumed to be TS motoneurons. Photographs of these antidromic responses were taken from the storage oscilloscope screen for subsequent analysis. The time between the onset of the nerve stimulation at antidromic threshold and the antidromically activated action potential was taken as the axonal conduction time of the motoneuron. After euthanasia, the nerve was fully exposed and the axonal conduction distance was measured along the nerve from the cathode of the proximal bipolar electrode pair to the point of microelectrode penetration into the spinal cord. Conduction velocity values were calculated as (conduction distance)/(antidromic conduction time). In some animals, selected TS motoneurons were also injected iontophoretically with HRP. These animals were perfused for anatomic studies reported elsewhere (Chen et al. 1991).
"C
y=O.O10x+5.6
o
r=0.95 (p 50 Hz with constant latency, though such high frequency stimulation often delayed or blocked the soma-dendritic (SD) c o m p o n e n t o f the spike, leaving only the initial segment (IS) component. When stimulation intensity was reduced below the threshold for an antidromic response, an orthodromic excitatory postsynaptic potential (EPSP), which had a latency longer than the antidromic spike, was often visible. Fig. 1 presents axon conduction distance, conduction velocity, and conduction time versus body weight for all 163 cells. Conduction distance (Fig. 1A) and velocity (Fig. 1B) increase in a linear fashion as weight increases. F o r each, the coefficient of linear correlation (r) is high and the correlation highly significant. In contrast, conduction time (Fig. 1C) remains stable as weight varies over nearly a three-fold range. The increase in conduction distance is matched closely by the increase in conduction velocity, so that, as indicated by the regression line, conduction time in a rat o f 630 g differs by less than 1% f r o m conduction time in a rat of 230 g.
1:3 C o
C
0
~0
400
5(X)
600
Body Weight (g) Fig. 1A-C. Axon conduction distance (A), conduction velocity (B), and antidromic conduction time (C) versus body weight for 163 TS motoneurons. Conduction distance and velocity increase in a linear fashion as weight increases. Conduction time remains unchanged as body weight increases nearly threefold
Discussion Axonal conduction velocities o f individual TS motoneutons of Sprague-Dawley rats, calculated from antidromic action potential latency and nerve length, were 30-67 m/s. Body weights were in the range of 230-630 g, corresponding to ages o f 6-16 weeks. This conduction velocity range is consistent with the findings of several previous studies in rats of comparable weight and/or age (Birren and Wall 1956; Brunner et al. 1980; Sato et al. 1985). F o r example, Birren and Wall (1956) found maxim u m sciatic nerve conduction velocities o f 31-59 m/s in Sprague-Dawley rats, 60-350 days old. In contrast, K a n d a and Hashizume (1989) and Gardiner and Kernell (1990) have reported somewhat higher values in single
345 unit studies f r o m medial gastrocnemius motoneurons. This difference m a y be due to age, gender, or strain differences, since K a n d a and Hashizume (1989) used Fischer rats ages 10-11 months, and Gardiner and Kernell (1990) used female Wistar rats. Birren and Wall (1956) and Sato et al. (1985) found that conduction velocity rises over the first 120 days, accompanying a rapid increase in weight. Velocity subsequently remains relatively constant despite further more gradual weight gain (Birren and Wall 1956; Sato et al. 1985), and eventually declines in old age ( K a n d a and Hashizume 1989). The salient finding of the present study is that this rise in conduction velocity matches almost perfectly the simultaneous increase in nerve length, so that conduction time does not change. This striking relationship has been noted previously only in kittens and documented only for the largest axons (i.e., those assessed by nerve volley measurement) (Hursh 1939a, b). The present data demonstrate its presence in rats over a considerable period of rapid growth and document it for the TS~imotoneuron population in general. A n u m b e r o f studies in cat have shown that myelinated nerve conduction velocity is proportional to fiber diameter (Hursh 1939a, b; Cullheim 1978; Westbury 1982). Assuming that this relationship also holds for the rat m o t o r axons studied here, the regression plotted in Fig. 1B for conduction velocity versus weight predicts that axon diameter increased 55 % when weight increased f r o m 230 g (about 6 weeks old) to 630 g (about 16 weeks old). Saitua and Alvarez (1988) studied sural nerve in Sprague-Dawley rats of different ages. They found that myelinated fibers continued growing up to the 14th week of age. F r o m weeks (~14, the mean diameter of myelinated axons increased 54%. Thus, their morphologic data combined with our physiologic data suggest that the relationship between fiber diameter and conduction velocity described in the cat is also present in the rat. As indicated above, H u r s h (1939a, b) found in 0-3 monthold kittens a similar constancy in conduction time in spite of rapid growth in nerve length. In addition, he noted the same relationship between fiber diameter and conduction velocity. Thus, in b o t h rats and cats over considerable periods of rapid development, axon length, axon diameter, and axon conduction velocity increase at nearly the same rate. While similar stability in peripheral nerve conduction time is not a p p a r e n t during h u m a n growth, m a n y recent studies (reviewed in Eyre et al. 1991) indicate that central m o t o r and sensory conduction time in humans are constant f r o m 2 years on and that their constancy m a y be attributable to proportional increase in fiber diameters. Eyre et al. (1991) speculate that stable central conduction time m a y help maintain stable sensorimotor integration during childhood by eliminating the changes in timing of feedback loops and other pathways that would otherwise a c c o m p a n y rapid growth. It is conceivable that the stability reported here in rat peripheral nerve conduction time serves a comparable purpose.
Ackno~vledgement. We thank Ms. Patricia A. Herchenroder and Ms. Dayna Maniccia for their excellent technical assistance. This study was supported in part by a grant from NIH (NS22189). References Birren JE, Wall PD (1956) Age changes in conduction velocity, refractory period, number of fibers, connective tissue space and blood vessels in sciatic nerve of rats. J Comp Neurol 104:1-16 Brunner R, Zimmermann P, Klul3mann FW (1980) Localization and neurophysiological properties of motoneurons of the M. triceps surae of the rat after retrograde labelling with evans blue. Cell Tissue Res 212:73-81 Chen XY, Carp JS, Wolpaw JR (1991) Motoneuron morphology in the rat. Soc Neurosci Abst 17:645 Cullheim S (1978) Relations between cell body size, axon diameter and axon conduction velocity of cat sciatic a-motoneurons stained with horseradish peroxidase. Neurosci Lett 8:17-20 Dorfman LJ, Bosley TM (1979) Age-related changes in peripheral and central nerve conduction in man. Neurology 29:38-44 Eyre JA, Miller S, Ramesh V (1991) Constancy of central conduction delays during development in man: investigation of motor and somatosensory pathways. J Physiol 434:441-452 Gardiner PF, Kernell D (1990) The "fastness" of rat motoneurons: time-course of afterhyperpolarization in relation to axonal conduction velocity and muscle unit contractile speed. Eur J Physiol 415: 762-766 Hopkins AP, Lambert EH (i 973) Age changes in conduction velocity of unmyelinated fibers. J Comp Neurol 147:547-552 Hursh JB (1939a) Conduction velocity and diameter of nerve fibers. Am J Physiol 127:131-139 Hursh JB (1939b) The properties of growing nerve fibers. Am J Physiol 127:140-153 Kanda K, Hashizume K (1989) Changing in properties of the medial gastrocnemius motor units in aging rats. J Neurophysiol 61:737-746 Knowlton GC, Britt LP (1949) Relation of height and age to reflex time. Am J Physiol 159: 576 Lafratta CW, Zalis A (1973) Age effects on sural nerve conduction velocity. Arch Phys Med Rehabil 54:475477 Morales FR, Boxer PA, Fung SJ, Chase MH (1987) Basic electrophysiological properties of spinal cord motoneurons during old age in the cat. J Neurophysiol 58:180-194 Norris AH, Shock NW, Wagman IH (1953) Age changes in the maximum conduction velocity of motor fibers of human ulnar nerves. J Appl Physiol 5 : 589-593 Saitua F, Alvarez J (1988) Do axons grow during adulthood? A study of caliber and microtubules of sural nerve axons in young, mature, and aging rats. J Comp Neurol 269:203-209 Sato A, Sato Y, Suzuki H (1985) Aging effects on conduction velocities of myelinated and unmyelinated fibers of peripheral nerves. Neurosci Lett 53:15-20 Trojaborg W (1976) Motor and sensory conduction in the musculocutaneous nerve. J Neurol Neurosurg Psychiat 39:890-899 Wagman IH, Lesse H (1952) Maximum conduction velocities of motor fibers of ulnar nerve in human subjects of various ages and sizes. J Neurophysiol 15:235-244 Wagner AL, Buchthal F (1972) Motor and sensory conduction in infancy and childhood: reappraisal. Develop Med Child Neurol 14:189-216 Westbury DR (1982) A comparison of the structures of c~- and ,l-spinal motoneurons of the cat. J Physiol 325:79-91 Wheeler SJ (1990) Effect of age on sensory nerve conduction velocity in the horse. Res Veter Sci 48:141-144 Wolpaw JR, Carp JS (1990) Memory traces in spinal cord. TINS 13:137-142 Wolpaw JR, Chert XY, Carp JS (1991) H-reflex in the freely moving rat: methods and initial data. Soc Neurosci Abstr 17:643
Experimental BrainResearch 9 Springer-Verlag1992
Constancy of motor axon conduction time during growth in rats Xiang Yang Chen, Jonathan S. Carp, and Jonathan R. Wolpaw Wadsworth Center for Laboratories and Research, New York State Department of Health and State University of New York, Albany, NY 12201~)509, USA Received December 5, 1991 / Accepted March 19, 1992
Summary. A x o n conduction distance, conduction velocity, and conduction time were measured for individual triceps surae m o t o n e u r o n s in Sprague-Dawley rats weighing 230-630 g (i.e., age range 6-16 weeks). Both conduction distance (nerve length) and velocity were closely correlated with weight (r = 0.95 and r = 0.82, respectively). In contrast, conduction time did not change as weight increased nearly threefold. This striking constancy is p r o b a b l y due to a corresponding increase in axon diameter. It could contribute to maintenance of stable m o t o r performance during rapid growth.
Key words: M o t o n e u r o n - M o t o r axon - N e r v e conduction - D e v e l o p m e n t - R a t
increase in m a x i m u m conduction velocity as measured by nerve volley. As a result, in spite of rapid change in body size, peripheral nerve conduction time remained the same, at least for the largest diameter axons assessed by the nerve volley measurement. In conjunction with efforts to define the physiologic and anatomic substrates of operantly conditioned plasticity in the spinal cord (Wolpaw and Carp 1990 for review; W o l p a w et al. 1991), we are studying triceps surae m o t o n e u r o n s in rat lumbar spinal cord. Initial studies suggested a strong correlation between animal age and axon conduction velocity. This study set out to document and define that relationship. The data indicate that a relation like that found in young kittens (Hursh 1939a, b) is present in rat over a considerable period of rapid growth.
Introduction Nerve conduction velocities change with age, especially during early life (Hursh 1939a, b; W a g m a n and Lesse 1952; Norris et al. 1953; Birren and Wall 1956; H o p k i n s and L a m b e r t 1973; Lafratta and Zalis 1973; D o r f m a n and Bosley 1979; Sato et al. 1985; Morales et al. 1987; K a n d a and Hashizume 1989; Wheeler 1990). In humans, m a x i m u m m o t o r and sensory nerve conduction velocities increase f r o m 33 m/s at one m o n t h of age to over 50 m/s at 4 years, remain stable through early and middle adulthood, and then begin to decrease at a b o u t age 50 (Knowlton and Britt 1949; W a g m a n and Lesse 1952; Wagner and Buchthal 1972; T r o j a b o r g 1976). C o m p a r a ble increases in early life and decreases with aging occur in the horse and in the rat (Wheeler 1990; Birren and Wall 1956; Sato et al. 1985; K a n d a and Hashizume 1989). The studies of H u r s h (1939a, b) are of particular interest. Unlike other studies which reveal only that conduction velocity tends to increase with growth particularly early in life, his studies found in kittens of 0 3 m o n t h s that the increase in leg length was exactly matched by an Correspondence to: X.Y. Chen, CNS Studies Section, Wadsworth Laboratories, P.O. Box 509, Albany, NY 12201-0509, USA
Material and methods Experiments were performed on 21 male Sprague-Dawley rats of 230-630 g (i.e., age range 6.16 weeks according to the supplier and our own observation). All animal procedures were in accord with DHEW Publ. No. (NIH) 85 23, "Guide for the Care and Use of Laboratory Animals," and had been reviewed and approved by the Institutional Animal Care and Use Committee of the Wadsworth Center. Surgical anaesthesia was induced with sodium pentobarbital (intraperitoneal, 60 mg/kg) and maintained with small additional doses (intraperitoneal, 15-20 mg/kg) at 30-60 min intervals throughout the 6-10 h course of the experiment. The trachea was cannulated. A T13 L1 laminectomy and longitudinal incision of the dura exposed the lumbar enlargement of the spinal cord (L3-L6). The animal was then positioned securely in a stereotaxic frame with ear bars, two vertebral clamps (one rostral to the laminectomy and one caudal) and a tail clamp. The animal was artificially ventilated and a bilateral pneumothorax was performed to provide the stability needed for intracellular recording. The tibial nerve of one side was exposed and the branches innervating the triceps surae (TS) muscles (medial gastrocnemius, lateral gastrocnemius and soleus) were cut as close to the main nerve as possible. The exposed tibial nerve was placed on two bipolar stimulating electrode pairs. One bipolar electrode pair was just proximal to the cut TS branches and the other was about 1 cm distal to these branches. Warmed mineral oil covered both the spinal cord and the exposed nerve. Heart rate
344 and expired pCO2 were monitored and maintained within normal physiological limits. Body temperature was kept at 37-38 ~ C and the temperatures of the oil pools were kept at 36-37 ~ C. At the end of the study, the anesthetized animal was euthanized with an overdose of pentobarbital. Intracellular recordings were obtained with glass mieroelectrodes (tip diam. about 2 ~m) filled with either 3 M KC1 solution (initial resistance 4-10 M~) or 6-8% horseradish peroxidase (HRP, Sigma type VI) in 0.5 M KCl-tris buffer (initial resistance 20-50 M~). The microelectrode began at the dorsal surface of the spinal cord and was advanced by a stepping microdrive in steps of 5 ~tm in order to impale motoneurons. During electrode advance, the proximal tibial nerve electrode pair delivered 1-Hz square pulses (0.05-ms duration) at an intensity three times the threshold for production of a volley at the cord dorsum. Intracellular recording and current injection were performed with a high impedance amplifier. Motoneurons were identified by their antidromic response to peripheral nerve stimulation. The antidromic nature of the action potential was confirmed by its origin from a fiat membrane potential (i.e., without a preceding synaptic potential) and its ability to follow high frequency stimulation (i.e., > 50-Hz) without latency shift. Motoneurons that were antidromically activated by the proximal bipolar electrode pair but not by the distal bipolar electrode pair were assumed to be TS motoneurons. Photographs of these antidromic responses were taken from the storage oscilloscope screen for subsequent analysis. The time between the onset of the nerve stimulation at antidromic threshold and the antidromically activated action potential was taken as the axonal conduction time of the motoneuron. After euthanasia, the nerve was fully exposed and the axonal conduction distance was measured along the nerve from the cathode of the proximal bipolar electrode pair to the point of microelectrode penetration into the spinal cord. Conduction velocity values were calculated as (conduction distance)/(antidromic conduction time). In some animals, selected TS motoneurons were also injected iontophoretically with HRP. These animals were perfused for anatomic studies reported elsewhere (Chen et al. 1991).
"C
y=O.O10x+5.6
o
r=0.95 (p 50 Hz with constant latency, though such high frequency stimulation often delayed or blocked the soma-dendritic (SD) c o m p o n e n t o f the spike, leaving only the initial segment (IS) component. When stimulation intensity was reduced below the threshold for an antidromic response, an orthodromic excitatory postsynaptic potential (EPSP), which had a latency longer than the antidromic spike, was often visible. Fig. 1 presents axon conduction distance, conduction velocity, and conduction time versus body weight for all 163 cells. Conduction distance (Fig. 1A) and velocity (Fig. 1B) increase in a linear fashion as weight increases. F o r each, the coefficient of linear correlation (r) is high and the correlation highly significant. In contrast, conduction time (Fig. 1C) remains stable as weight varies over nearly a three-fold range. The increase in conduction distance is matched closely by the increase in conduction velocity, so that, as indicated by the regression line, conduction time in a rat o f 630 g differs by less than 1% f r o m conduction time in a rat of 230 g.
1:3 C o
C
0
~0
400
5(X)
600
Body Weight (g) Fig. 1A-C. Axon conduction distance (A), conduction velocity (B), and antidromic conduction time (C) versus body weight for 163 TS motoneurons. Conduction distance and velocity increase in a linear fashion as weight increases. Conduction time remains unchanged as body weight increases nearly threefold
Discussion Axonal conduction velocities o f individual TS motoneutons of Sprague-Dawley rats, calculated from antidromic action potential latency and nerve length, were 30-67 m/s. Body weights were in the range of 230-630 g, corresponding to ages o f 6-16 weeks. This conduction velocity range is consistent with the findings of several previous studies in rats of comparable weight and/or age (Birren and Wall 1956; Brunner et al. 1980; Sato et al. 1985). F o r example, Birren and Wall (1956) found maxim u m sciatic nerve conduction velocities o f 31-59 m/s in Sprague-Dawley rats, 60-350 days old. In contrast, K a n d a and Hashizume (1989) and Gardiner and Kernell (1990) have reported somewhat higher values in single
345 unit studies f r o m medial gastrocnemius motoneurons. This difference m a y be due to age, gender, or strain differences, since K a n d a and Hashizume (1989) used Fischer rats ages 10-11 months, and Gardiner and Kernell (1990) used female Wistar rats. Birren and Wall (1956) and Sato et al. (1985) found that conduction velocity rises over the first 120 days, accompanying a rapid increase in weight. Velocity subsequently remains relatively constant despite further more gradual weight gain (Birren and Wall 1956; Sato et al. 1985), and eventually declines in old age ( K a n d a and Hashizume 1989). The salient finding of the present study is that this rise in conduction velocity matches almost perfectly the simultaneous increase in nerve length, so that conduction time does not change. This striking relationship has been noted previously only in kittens and documented only for the largest axons (i.e., those assessed by nerve volley measurement) (Hursh 1939a, b). The present data demonstrate its presence in rats over a considerable period of rapid growth and document it for the TS~imotoneuron population in general. A n u m b e r o f studies in cat have shown that myelinated nerve conduction velocity is proportional to fiber diameter (Hursh 1939a, b; Cullheim 1978; Westbury 1982). Assuming that this relationship also holds for the rat m o t o r axons studied here, the regression plotted in Fig. 1B for conduction velocity versus weight predicts that axon diameter increased 55 % when weight increased f r o m 230 g (about 6 weeks old) to 630 g (about 16 weeks old). Saitua and Alvarez (1988) studied sural nerve in Sprague-Dawley rats of different ages. They found that myelinated fibers continued growing up to the 14th week of age. F r o m weeks (~14, the mean diameter of myelinated axons increased 54%. Thus, their morphologic data combined with our physiologic data suggest that the relationship between fiber diameter and conduction velocity described in the cat is also present in the rat. As indicated above, H u r s h (1939a, b) found in 0-3 monthold kittens a similar constancy in conduction time in spite of rapid growth in nerve length. In addition, he noted the same relationship between fiber diameter and conduction velocity. Thus, in b o t h rats and cats over considerable periods of rapid development, axon length, axon diameter, and axon conduction velocity increase at nearly the same rate. While similar stability in peripheral nerve conduction time is not a p p a r e n t during h u m a n growth, m a n y recent studies (reviewed in Eyre et al. 1991) indicate that central m o t o r and sensory conduction time in humans are constant f r o m 2 years on and that their constancy m a y be attributable to proportional increase in fiber diameters. Eyre et al. (1991) speculate that stable central conduction time m a y help maintain stable sensorimotor integration during childhood by eliminating the changes in timing of feedback loops and other pathways that would otherwise a c c o m p a n y rapid growth. It is conceivable that the stability reported here in rat peripheral nerve conduction time serves a comparable purpose.
Ackno~vledgement. We thank Ms. Patricia A. Herchenroder and Ms. Dayna Maniccia for their excellent technical assistance. This study was supported in part by a grant from NIH (NS22189). References Birren JE, Wall PD (1956) Age changes in conduction velocity, refractory period, number of fibers, connective tissue space and blood vessels in sciatic nerve of rats. J Comp Neurol 104:1-16 Brunner R, Zimmermann P, Klul3mann FW (1980) Localization and neurophysiological properties of motoneurons of the M. triceps surae of the rat after retrograde labelling with evans blue. Cell Tissue Res 212:73-81 Chen XY, Carp JS, Wolpaw JR (1991) Motoneuron morphology in the rat. Soc Neurosci Abst 17:645 Cullheim S (1978) Relations between cell body size, axon diameter and axon conduction velocity of cat sciatic a-motoneurons stained with horseradish peroxidase. Neurosci Lett 8:17-20 Dorfman LJ, Bosley TM (1979) Age-related changes in peripheral and central nerve conduction in man. Neurology 29:38-44 Eyre JA, Miller S, Ramesh V (1991) Constancy of central conduction delays during development in man: investigation of motor and somatosensory pathways. J Physiol 434:441-452 Gardiner PF, Kernell D (1990) The "fastness" of rat motoneurons: time-course of afterhyperpolarization in relation to axonal conduction velocity and muscle unit contractile speed. Eur J Physiol 415: 762-766 Hopkins AP, Lambert EH (i 973) Age changes in conduction velocity of unmyelinated fibers. J Comp Neurol 147:547-552 Hursh JB (1939a) Conduction velocity and diameter of nerve fibers. Am J Physiol 127:131-139 Hursh JB (1939b) The properties of growing nerve fibers. Am J Physiol 127:140-153 Kanda K, Hashizume K (1989) Changing in properties of the medial gastrocnemius motor units in aging rats. J Neurophysiol 61:737-746 Knowlton GC, Britt LP (1949) Relation of height and age to reflex time. Am J Physiol 159: 576 Lafratta CW, Zalis A (1973) Age effects on sural nerve conduction velocity. Arch Phys Med Rehabil 54:475477 Morales FR, Boxer PA, Fung SJ, Chase MH (1987) Basic electrophysiological properties of spinal cord motoneurons during old age in the cat. J Neurophysiol 58:180-194 Norris AH, Shock NW, Wagman IH (1953) Age changes in the maximum conduction velocity of motor fibers of human ulnar nerves. J Appl Physiol 5 : 589-593 Saitua F, Alvarez J (1988) Do axons grow during adulthood? A study of caliber and microtubules of sural nerve axons in young, mature, and aging rats. J Comp Neurol 269:203-209 Sato A, Sato Y, Suzuki H (1985) Aging effects on conduction velocities of myelinated and unmyelinated fibers of peripheral nerves. Neurosci Lett 53:15-20 Trojaborg W (1976) Motor and sensory conduction in the musculocutaneous nerve. J Neurol Neurosurg Psychiat 39:890-899 Wagman IH, Lesse H (1952) Maximum conduction velocities of motor fibers of ulnar nerve in human subjects of various ages and sizes. J Neurophysiol 15:235-244 Wagner AL, Buchthal F (1972) Motor and sensory conduction in infancy and childhood: reappraisal. Develop Med Child Neurol 14:189-216 Westbury DR (1982) A comparison of the structures of c~- and ,l-spinal motoneurons of the cat. J Physiol 325:79-91 Wheeler SJ (1990) Effect of age on sensory nerve conduction velocity in the horse. Res Veter Sci 48:141-144 Wolpaw JR, Carp JS (1990) Memory traces in spinal cord. TINS 13:137-142 Wolpaw JR, Chert XY, Carp JS (1991) H-reflex in the freely moving rat: methods and initial data. Soc Neurosci Abstr 17:643
