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D J Stehouwer

Publications and source records attributed to D J Stehouwer.

At least 19 recordsLinked to original sources

Kinematic analyses of air-stepping of neonatal rats after mid-thoracic spinal cord compression.

Although human infants suffer traumatic spinal cord injury, appropriate animal models have not been developed. The consequences of neonatal injury are not necessarily the same as in adults, so treatments designed for adults may not generalize to infants. Therefore, understanding the effects of traumatic injury to the developing cord is important. In this experiment, mid-thoracic spinal cords of 4-day-old rats were compressed with forceps by 0% (sham), 90% or 95% of the uncompressed width. On postoperative day (POD) 1 or 11, rats were suspended in harnesses and administered L-DOPA to activate locomotor circuits. Slight modifications of interlimb coordination remained on POD 11 following the lesser compression, whereas the amount of hindlimb air-stepping, step rates, step lengths and coordination were reduced and declined post-operatively following the greater compression. Lesions were proportional to severity of compression. Progressive motor dysfunction during air-stepping revealed deficits in descending control of lumbar circuits, whereas previous reports of recovery of overground walking probably reflect activation of reflex mechanisms caudal to the transection.

Animals↗

L-DOPA-induced air-stepping in the preweanling rat: electromyographic and kinematic analyses.

Ontogenetic changes in intralimb coordination may result from maturation of the central pattern for locomotion, maturation of peripheral efferents, changes in afferent modulation of the centrally generated pattern, interactions with the substrate, biomechanical changes within the limb itself, or a combination of these. Electromyograms obtained from three hindlimb extensors of rats on Postnatal Days (PND) 5, 10, 15, or 20, during episodes of coordinated L-DOPA-induced air-stepping, showed that muscle activation preceded extension of the corresponding joints at all ages. The delay between the onset of extensor activity and the onset of joint extension increased during ontogeny and was greatest at PND 20. Ontogenetic changes in the relative timing of muscle activity and corresponding joint movements probably resulted from changes in biomechanical factors, changes in afferent modulation of central motor output, or both.

Afferent Pathways↗

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats.

We studied the ability of L-DOPA (100 mg/kg, subcutaneous) to elicit air-stepping in decerebrate and sham-operated Sprague-Dawley rats from postnatal Day 5 through postnatal Day 20. The most common gait consisted of fore- and hindlimb alternation, but between 10 and 20 days of age, patterns of coordination resembling swimming, in which the forelimbs remained adducted, and galloping became more frequent in both decerebrate and sham-operated rats. Because episodes of galloping were rarely more than two or three step cycles in length, our analyses focused on episodes of stepping in which limbs within the girdles stepped in alternation and diagonal pairs of limbs moved in synchrony ("trot"). The rate of stepping of both decerebrate and sham-operated rats increased from about 2.9 steps/s at Day 5 to about 4 steps/s at Day 20. In both groups, this increase was found to result from a decrease in the duration of the retraction phase of the step cycle. Amplitudes of movement at the wrist, knee, and ankle increased with age in both decerebrate and sham-operated neonates, whereas those of the shoulder, elbow, and hip did not change in either group. The timing of movements at joints within each limb also changed similarly with age in sham-operated and decerebrate pups. During development, forelimb movement was increasingly led by the wrist, which was followed by the elbow and then finally by the shoulder. Hindlimb movements were increasingly led by the knee, followed by the ankle, and finally by the hip. At all ages, diagonal limbs moved in synchrony, and heterolateral limbs within each girdle moved in antiphase. However, the phase relationship between hindlimb and forelimb movements changed both in sham-operated rats and in decerebrate rats during ontogeny. On Day 5, movement of each hindlimb was phase-delayed relative to that of the diagonal forelimb whereas on Days 15 and 20, the hindlimb was phase-advanced. The parallel emergence of different gaits and the similarity of coordination during diagonal progression in sham-operated and decerebrate pups show that age-related changes in gait are mediated no more rostrally than the midbrain.

Age Factors↗

The NMDA antagonist, MK-801, alters L-DOPA-induced air-stepping in neonatal rats.

Administration of L-DOPA (sc) to neonatal rats suspended in harnesses induces coordinated stepping of all four limbs (diagonal progression; L-DOPA-induced air-stepping) by 5 days of age. Because NMDA also induces locomotion in several species, NMDA receptor activation may be required for L-DOPA to elicit coordinated air-stepping. The purpose of the present experiment was to determine if the NMDA receptor antagonist, MK-801, would block L-DOPA-induced air-stepping in developing rats. Neonatal rats administered MK-801 alone rarely air-stepped with the forelimbs or hindlimbs in a coordinated fashion, whereas those treated with L-DOPA alone primarily stepped with all four limbs using a diagonal progression pattern during the session. In contrast, the number of limbs that stepped during the session was gradually altered in 5- to 20-day-old rats treated with MK-801 + L-DOPA. Gaits of those rats progressed from diagonal progression to extension of the forelimbs beneath the chin with hindlimb alternation, to forelimb extension without hindlimb activity. Twenty-day-olds treated with MK-801 + L-DOPA subsequently became completely inactive when the forelimbs dropped from their elevated position beneath the chin. In addition to the sequence just described, 15-day-old rats treated with the lowest concentration of MK-801 + L-DOPA occasionally stepped with one pair of homolateral limbs or stepped with the hindlimbs in near synchrony while the forelimbs either stepped in alternation, were extended beneath the chin or groomed the face. Because limb participation during L-DOPA-induced air-stepping was altered in neonatal rats pretreated with MK-801, NMDA receptor activation may be important for locomotor coordination (gait).

Animals↗

Dopamine D1 and D2 antagonists block L-DOPA-induced air-stepping in decerebrate neonatal rats.

L-DOPA administered to neonatal rats suspended in air elicits stereotypic locomotor activation termed air-stepping; it can be dose-dependently blocked by a dopamine (DA) D1 or D2 antagonist. In order to determine whether the forebrain is the site for this blockade, decerebrate 5-day-old rats were pretreated subcutaneously with either the DA D1 receptor antagonist SCH 23390 (16 mg/kg), the DA D2 receptor antagonist spiperone (6 mg/kg), or vehicle before receiving 100 mg/kg L-DOPA. Both antagonists blocked L-DOPA-induced air-stepping in both decerebrate and intact pups.

Animals↗

A kinematic comparison of L-DOPA-induced air-stepping and swimming in developing rats.

In Experiment 1, rats of 5, 10, 15, and 20 days of age were injected with L-DOPA to elicit stepping and videotaped while suspended in air and in warm water. Inter- and intralimb coordination were similar for L-DOPA-induced air-stepping and swimming at all ages. Other parameters of locomotion, such as step length and step rate, varied by substrate. In Experiment 2, pups of 5 to 20 days of age received an injection of L-DOPA or the vehicle and were videotaped while freely swimming. L-DOPA-induced free swimming was more stereotyped and "automatonlike" than that of vehicle-injected animals. Through 15 days of age, all pups swam using all four limbs, but L-DOPA induced stricter synchrony of movement in diagonal limbs than was used by pups injected with the vehicle. At postnatal Day 20, vehicle-injected pups adopted the adult swimming pattern in which only the hindlimbs were used, whereas L-DOPA-injected pups continued to use the immature pattern, diagonal progression with all four limbs. These results suggest that L-DOPA-induced air-stepping and swimming are manifestations of the same central mechanisms and that parameters of L-DOPA-induced stepping are modified by the sensory and/or biomechanical effects of the substrate. Although the free swimming of L-DOPA-injected pups was kinematically similar to vehicle-treated pups, L-DOPA retarded transition to the adult swimming pattern.

Aging↗

L-DOPA and quipazine elicit air-stepping in neonatal rats with spinal cord transections.

Acute mid-thoracic spinal cord transection eliminates hindlimb air-stepping in neonatal rats suspended in harnesses and administered L-DOPA. Because spinal cord transection eliminates all descending inputs to the hindlimb locomotor circuits, this experiment determined if coadministration of L-DOPA and quipazine (serotonin receptor agonist) would induce hindlimb air-stepping in rat pups 24 hr after transection. Hindlimb steps of spinally transected pups that received L-DOPA or quipazine alone were infrequent and slow; hindlimb steps induced by L-DOPA + quipazine occurred more frequently and were faster than those elicited by either drug alone. These findings suggest that catecholaminergic and serotonergic systems both contribute to hindlimb stepping.

Animals↗

An aromatic L-amino acid decarboxylase inhibitor blocks L-dopa-induced air-stepping in neonatal rats.

Rat pups suspended in air and administered L-DOPA engage in a locomotor behavior termed air-stepping. The role of L-DOPA itself was investigated by administering several doses of an aromatic L-amino acid decarboxylase inhibitor, NSD 1015, prior to 100 mg/kg L-DOPA to 5-day-old rats. NSD 1015 dose-dependently increased the latency to onset and decreased the duration of L-DOPA-induced air-stepping. Thus L-DOPA induces air-stepping only after its conversion to dopamine and/or noradrenaline.

Animals↗

L-dopa-induced air-stepping in preweanling rats. I. Effects of dose and age.

The effects of several doses of L-DOPA (25, 50, 75 and 100 mg/kg) on air-stepping were studied in rats on the day of birth and on 5, 10, 15 and 20 days of age. Occurrence of air-stepping increased and latency to air-stepping generally decreased with dose except at 10 days of age; duration of air-stepping increased with increasing dose of L-DOPA at every age. The occurrence of a variety of air-stepping gaits was age-dependent. On the day of birth, air-stepping consisted primarily of episodes of forelimb alternation; on days 5-20, diagonal progression was the predominant gait, but beginning at day 10, episodes of air-swimming, air-galloping and other locomotor patterns were interspersed. Not only could the durations of most of these gaits be increased with increasing dose of L-DOPA, but at some ages, increasing the dose of L-DOPA led to gait changes.

Aging↗

L-dopa-induced air-stepping in preweanling rats. II. Kinematic analyses.

Coordination of air-stepping elicited by subcutaneous injections of L-DOPA (25-100 mg/kg) was studied in rats from the day of birth through 20 days of age. Results revealed a nearly linear increase in the rate of stepping from about 1.5 steps/s at day 0 to about 4.5 steps/s at day 20, independent of the dose of L-DOPA. The ontogenetic increase in the rate of stepping was found to result from decreases in the duration of both retraction and protraction phases of the step cycle, but the decrease in the retraction phase was greater. There was an ontogenetic increase in the amplitude of movement at the wrist, knee and ankle joints, a slight decline in the amplitude of movement at the elbow and little change in amplitude at either the shoulder or hip. The relative timing of movements at joints within each limb also changed with age. Forelimb movements were led by the wrist throughout development, followed by the elbow and then the shoulder, which increasingly lagged behind the other two joints of the forelimb. Hindlimb movements were increasingly led by the knee, followed by the ankle and then the hip. Diagonal progression, in which the diagonal limbs moved in phase with each other and in antiphase with the contralateral limb of the same girdle, was seen at all ages. However, other gaits, which resembled galloping (air-galloping) and swimming (air-swimming), became more prevalent between 10 and 20 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Noradrenergic alpha-1 and alpha-2 antagonists block L-dopa-induced air-stepping in neonatal rats.

Five-day-old rat pups suspended in air and administered L-3,4-dihydroxyphenylalanine (L-DOPA) engage in a highly stereotyped and coordinated locomotor behavior termed air-stepping. L-DOPA is a precursor for dopamine and noradrenaline and one or both of these neurotransmitters could play a role in L-DOPA-induced air-stepping. The role of noradrenaline was investigated by assessing the abilities of the alpha-1 noradrenergic receptor antagonist prazosin and the alpha-2 noradrenergic receptor antagonist idazoxan to block L-DOPA-induced air-stepping in 5-day-old rats. Both antagonists decreased the duration of air-stepping. In addition, prazosin altered the topography of air-stepping by interfering with coordination of the hindlimbs. The results suggest that alpha-1 and alpha-2 noradrenergic receptor subtypes are involved in L-DOPA-induced air-stepping.

Adrenergic alpha-1 Receptor Antagonists↗

Dopamine D1 and D2 antagonists block L-dopa-elicited air-stepping in neonatal rats.

When administered to rat pups that have been suspended in air, L-3,4-dihydroxyphenylalanine (L-DOPA) induces a highly stereotypic locomotor response referred to as air-stepping. In order to determine the respective roles of dopamine D1 and D2 receptors in the expression of air-stepping, the abilities of the selective D1 antagonist SCH 23390 and the selective D2 antagonist spiperone to block L-DOPA-induced air-stepping in 5-day-old rat pups were assessed. Both antagonists increased latency to onset, and both decreased total duration of air-stepping by decreasing the number and length of air-stepping episodes. Neither SCH 23390 nor spiperone altered the topography of the air-stepping response; however, subjects receiving lower doses of spiperone spent significantly more time with the body dorsiflexed and limbs extended (extension/tremor activity) than did control subjects. The results suggest that both the D1 and D2 receptor subtypes are involved in the production of L-DOPA-induced locomotor activity.

Animals↗

Development of anuran locomotion: ethological and neurophysiological considerations.

There are dramatic quantitative and qualitative differences in the locomotor behavior of larval and juvenile frogs. Larvae (tadpoles) are primarily herbivourous and rely heavily on locomotion via undulations to acquire food and avoid predation. After metamorphosis, juvenile frogs adopt a carnivorous lifestyle and capture prey and avoid predators by remaining motionless in a place of concealment. When they must move, frogs locomote by means of ballistic hops or by more conventional walking. However, locomotion of both tadpoles and frogs can be considered of two fundamental functional types: (a) startle and escape; and (b) sustained locomotion. Neural mechanisms underlying startle responses and sustained locomotion in larvae and juveniles are described and possible ontogenetic relationships those behaviors are proposed. The role of different parts of the nervous system in the ontogeny of locomotion, as well as nonneuronal factors, are described. Results show that the transition from tadpole-like behavior to frog-like behavior is not a simple function of maturation of central locomotor controls. Rather, it results from a complex interaction of central nervous system maturation, morphological change, and a change in habitat preference. Examples of similar multidimensional control of behavioral ontogeny in other species are described, and it is argued that to understand the ontogeny of behavior, one must investigate contributions made at all levels, from the neuronal to the environmental.

Animals↗

L-dopa-induced air-stepping in developing rats.

Rat pups at postnatal day (PN) 0, 5, 10, 15, and 20 were injected with 100 mg/kg L-3,4-dihydroxyphenylalanine (L-DOPA; s.c.) or the control vehicle and suspended in a sling. L-DOPA induced highly stereotyped air-stepping that varied along several dimensions across development. The latency to air-stepping was constant across age, but the duration was significantly shorter in the older pups. At all ages, air-stepping was preceded or accompanied by raising of the head and dorsiflexion of the tail. The rate of stepping increased across age and gait varied with age. At PN 0, L-DOPA induced alternating forelimb movements with little involvement of the hindlimbs. At PN 5 and 10, both forelimb and hindlimb alternation were observed. At PN 10 and 15 swimming-like behavior emerged, and at PN 10, 15, and 20, episodes of galloping were interspersed with limb alternation. Thus, highly coordinated activity can be elicited by L-DOPA at all ages studied when the rat pup needs not support its own body weight and has no contact with a substrate. Drug-induced air-stepping promises to be an important new paradigm for pharmacological and behavioral studies of the development of locomotor controls in mammals.

Animals↗

Sparing and recovery of function in spinal larval frogs (Rana catesbeiana): effect of level of transection.

Bullfrog tadpoles with cervical or midthoracic transection of the spinal cord were allowed to recover for 5 weeks, at which time axonal growth across the transection site was assessed by transport of horseradish peroxidase. Weekly behavioral tests included those for posture, spontaneous locomotion, cutaneously elicited swimming, and intersegmental coordination. Behavioral and electrophysiological assessments suggest that behavioral recovery depends, at least in part, on the growth of fibers across the transection site. Anatomical and behavioral recovery does not appear to differ with the level of spinal transection, but there was greater sparing of posture, spontaneous locomotion, and stimulus-induced locomotion in tadpoles with thoracic transection of the spinal cords.

Animals↗

Metamorphosis of behavior in the bullfrog (Rana catesbeiana).

This study describes the development of different spontaneous and elicited behaviors of frogs and their relationship to morphological, physiological, and ecological changes of metamorphosis. Tadpoles were studied at all stages of development from Stage XVIII, the onset of metamorphosis, to Stage XXV, when metamorphosis of the froglets is complete. Behaviors examined included development of forelimb postural support, postural responses to vestibular stimulation, the hindlimb withdrawal reflex, the corneal reflex, ocular mobility, and habitat preference. Results showed that these behaviors differ markedly in their timing and rate of maturation. Forelimb postural support and postural responses to vestibular stimulation improved gradually between Stages XX and XXV. In contrast, the threshold of the hindlimb withdrawal reflex remained essentially unchanged until Stage XXV, when it increased suddenly and dramatically. The corneal reflex appeared suddenly at Stage XXI with a threshold similar to that of juvenile frogs. The ability to move the eyes in response to visual or vestibular stimulation was pronounced in tadpoles, but gradually declined between Stage XVIII and Stage XXV, so that froglets showed almost no ocular mobility. The preference of metamorphosing frogs for deep water, shallow water, shoreline, or land were examined in an aquarium during a 24-hr observation period using time-lapse videotape recordings. Results showed that tadpoles spent progressively less time in deep water and shallow water as metamorphosis proceeded. Preference for land emerged suddenly at Stage XXII and remained high thereafter. There were no stage-related differences in preferences for the shoreline.

Animals↗