Kenro Kanda

Reflex responses of human thigh muscles to non-noxious sural stimulation during stepping.

An investigation of reflex responses of leg muscles to sural stimulation during stepping was performed on human subjects. Non-noxious electrical stimulation applied during the swing phase or the latter half of the stance phase produced a mixed increase and decrease of EMG activity in the hamstring muscles. No response or very weak response was observed when the same stimulus was applied during either quiet standing or various levels of constant voluntary effort at varying hip and knee joint angles.

Dynamic and static sensitivities of muscle spindle primary endings in aged rats to ramp stretch

Responses of the presumed primary sensory endings of de-efferented muscle spindles to a ramp stretch were investigated in the medial gastrocnemius muscle of male Fischer 344 rats of two age groups (i.e. 10-14 and 28-30 months) anesthetized with urethane and chloralose. The static sensitivity was similar for both middle-aged and aged rats, although the discharge frequency was lower for aged rats when compared at the same muscle length. The value of the dynamic index was significantly lower in aged rats than in middle-aged rats, suggesting a decrease in the dynamic sensitivity of muscle spindle primary endings in aged rats.

Differential effects of aging on motoneurons and peripheral nerves innervating the hindlimb and forelimb muscles of rats

We examined the number and size of ulnar (forelimb) and medial gastrocnemius (MG, hindlimb) motoneurons in middle-aged (9 months of age) and aged (27 months of age) male Fischer 344 rats. Morphological properties of the ulnar and the MG nerves were also studied. No significant difference was found in the mean number of the ulnar motoneurons between the two age groups, while that of MG motoneurons was significantly less in aged animals. A decrease in the number of myelinated fibers (including both afferent and efferent fibers) in the ulnar nerves was less than that in the MG nerves, although the age difference was not significant in either of the nerves. Soma atrophy of aged motoneurons was found in both MG and ulnar motor nuclei. The mean fascicular areas and myelinated fiber diameters were significantly increased in both the MG and the ulnar nerves in aged rats, but these were less pronounced for the ulnar nerve. The results indicate that most ulnar motoneurons, unlike MG motoneurons, survive at least to the age of 27 months. Morphological changes in the peripheral nerves were also less for the ulnar nerve than for the MG nerve. Thus, we conclude that the effects of aging on motoneurons and peripheral nerves innervating MG muscle of the hindlimb are greater than those innervating forelimb muscles.

Effects of long-term physical exercise on age-related changes of spinal motoneurons and peripheral nerves in rats.

We examined the number and size of motoneurons and myelinated nerve fibers innervating the medial gastrocnemius (MG) muscle in the hindlimb of rats that were subjected to swimming for 10 months (30 min, 3 days/week) from 17 to 27 months of age. The number of MG motoneurons in exercised aged rats was slightly, but not significantly, greater than that in sedentary aged rats, and the number for both aged groups was significantly less compared to that in middle-aged (17-month-old) rats. The size of motoneuronal somata in the exercised aged rats was significantly larger than that in sedentary aged rats. Morphological parameters (fascicular area, fiber density, and axonal diameter) for the MG nerve in the exercised rats showed intermediate values between those for middle-aged and sedentary aged rats, although all of the differences in the means between groups were not significant. Thus, the overall changes seen in the exercised rats seem less compared to the changes in the sedentary rats, suggesting that long-term moderate exercise retards the progressive changes in motoneurons and peripheral nerves that develop in old age.

Developmental alterations in NMDA receptor-mediated currents in neonatal rat spinal motoneurons

Postnatal development of N-methyl-D-aspartate (NMDA) receptors expressed in motoneurons was studied by tight-seal whole-cell recordings from identified motoneurons in slices of neonatal rat spinal cord. The magnitude of NMDA-induced currents was large during the early postnatal period, and then it decreased gradually through postnatal day (PND) 15. The pharmacological properties of NMDA-induced currents altered during this period, suggesting that the combination of NMDA receptor subunits changes during development. The magnitude of the NMDA receptor-mediated component of excitatory postsynaptic current evoked by electrical stimulation of an adjacent neuron also decreased from PNDs 1-5 through PNDs 11-15. NMDA receptors appear to underlie the mechanisms of activity-dependent development of spinal motoneurons during early postnatal life.

Developmental alterations in NMDA receptor-mediated [Ca2+]i elevation in substantia gelatinosa neurons of neonatal rat spinal cord

Using spinal cord slices prepared from neonatal rats, the intracellular free Ca2+ concentration ([Ca2+]i) in neurons located in the dorsal horn substantia gelatinosa (SG) was measured with microscopic fluorometry by loading fura 2-AM into neurons. Developmental alterations in the elevation of [Ca2+]i elicited by the glutamate analogs, NMDA and AMPA, were investigated from postnatal day (PNDs) 1 to 17. During the 1st week of postnatal life, when neuronal maturation of the SG is known to take place, the NMDA response remained large or even slightly increased. It subsequently showed a gradual decline. This pattern of postnatal changes is consistent with previously reported autoradiographic studies on NMDA-binding sites. The affinity of receptors for NMDA was found to decrease constantly during the period examined. The AMPA response and resting [Ca2+]i showed no significant developmental changes. Neonatal treatment with capsaicin, which has been shown to degenerate fine primary afferent fibers terminating in the SG, delayed the developmental decline in the NMDA-induced [Ca2+]i response. It is suggested that the number and the molecular properties of NMDA receptors expressed in the SG change during early postnatal neuronal maturation. The temporal coincidence between postnatal alteration in NMDA-induced [Ca2+]i elevation and neuronal maturation of the SG may indicate that intracellular Ca2+ regulated by NMDA receptor activation is related to postnatal neuronal maturation. Activation of fine primary afferent fibers may contribute to the observed developmental alterations in the NMDA response of SG neurons.

Neuronal dropout is greater in hindlimb motor nuclei than in forelimb motor nuclei in aged rats

The number of forelimb, ulnar (U) and hindlimb, medial gastrocnemius (MG) motoneurons labeled with retrograde axonal transport of horseradish peroxidase was examined in young and aged rats. No significant difference was found between the mean number of U motoneurons in young and aged rats, whereas the mean number of MG motoneurons was significantly lower in aged rats than in young rats. These results suggest that motoneuronal dropout is greater in hindlimb motor nuclei than in forelimb motor nuclei, which may contribute to differential changes in forelimb and hindlimb muscles with increasing age.

The role of vertebral column muscles in level versus upslope treadmill walking—An electromyographic and kinematic study

To gain insight into the neural mechanisms controlling vertebral column movement and its role in walking, we performed kinematic and electromyographic (EMG) studies on cats during level and upslope treadmill walking. Kinematic data of the limbs and vertebral column were obtained with a high-speed camera synchronized with EMG recordings from levels T10, L1, and L5 of m. longissimus dorsi (Long). During a single-step cycle at all upslope angles, vertebral movement in the lateral (left-right), cranial-caudal (forward-backward), and dorsal-ventral (upward-downward) directions was observed. Lateral movements were produced by forelimb take-off and hindlimb landing, and forward and upward movements were produced by hindlimb extension. During the single-step cycle, each of the three epaxial muscles, m. multifidus, m. iliocostalis, and Long, showed two bilateral EMG bursts. The onset of the EMG bursts coincided with the left-right movements, suggesting that epaxial muscle activity depresses lateral movement. The termination of the EMG bursts correlated with the forward and downward phase of the step cycle, suggesting that contraction of the epaxial muscles produces forward and downward movements. EMG bursts of the epaxial muscles increase the stiffness and produce inwardly movements to decrease the lateral movements of the vertebral column and the termination of EMG bursts control the movements into cranial and ventral direction of the vertebral column. The results suggest that the rhythmic EMG bursts in the epaxial muscles are produced by pattern generators, and the timing of EMG bursts among the different levels of the epaxial muscles are altered by walking condition input via peripheral afferents and descending pathways.

Overloading a muscle does not alter the rate of motoneuronal loss in aged rats

Effects of increased activity on neuronal cell death was investigated in the motor nuclei innervating normal and overloaded medial gastrocnemius (MG) muscles of Fischer 344 rats. The MG muscle was overloaded by the unilateral surgical ablation of synergists at the age of 17 months (group A) or 24 months (group B). When the rats reached the age of 24 and 28 months (group A) or 30 months (group B), motoneurons innervating the MG muscle were labeled bilaterally with horseradish peroxidase injected into the MG nerve. The wet weight of the muscle on the operated side was consistently heavier than that of the contralateral, intact side. The number of labeled neurons decreased with advancing age, and there was no difference in the magnitude of decline found between motor nuclei innervating intact and hypertrophied muscles. Thus, overloading the MG muscle did not retard or accelerate the age-related loss of motoneurons innervating this muscle. These findings indicate that the causal relationship between motoneuronal activity and death with advancing age needs to be studied further.

Recovery of motor-unit function after peripheral nerve injury in aged rats

The potential capacity of aged motoneurons for the reconstruction of motor-units after nerve crush injury was studied in the medial gastrocnemius (MG) muscle of male Fischer rats. The MG nerve in middle-aged (8 months old) and aged (24 months) rats was aseptically crushed under pentobarbital anesthesia. After a 3-month recovery period, the animal was reanesthetized and physiological properties of individual motor-units were recorded. The three different types (fast twitch, fatigable: FF; fast twitch, fatigue resistant: FR and slow twitch: S) of normal motor-unit organization were restored in both middle-aged and aged reinnervated muscles as measured by their relative distributions, mean twitch contraction times and mean tetanic tensions. Some reinnervated units in both aged and middle-aged rats produced a large tetanic tension which exceeded the range for intact units. These findings indicate that aged motoneurons maintain their ability for axonal regenerating and muscle fiber innervation to reestablish normal function of motor-units.