| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Spinal Cord Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada; 2Department of Physiology, Biophysics and Neuroscience, Centro de Investigacion y de Estudios Avanzados, Mexico City, Mexico; and 3The Salk Institute, San Diego, California
Submitted 18 February 2005; accepted in final form 21 May 2005
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
; Forssberg 1979; Prochazka et al. 1978; Wand et al. 1980) and decerebrate (Forssberg 1979) cats. Its occurrence in cats with chronic, lower thoracic, spinal lesions (Forssberg 1979; Forssberg et al. 1977) indicates that the stumbling reflex can be organized at the level of the lumbar spinal cord. An analogous response exists in adult humans (Eng et al. 1994; Schillings et al. 1996; Van Wezel et al. 1997; Zehr et al. 1997) and infants (Lam et al. 2003).
In the cat, the stumbling corrective reflex evoked during swing activates knee flexors, ankle extensors (Buford and Smith 1993; Forssberg 1979; Forssberg et al. 1977; Prochazka et al. 1978; Wand et al. 1980), and hip flexors (Pratt et al. 1996). In the ankle flexor tibialis anterior (TA), there is an initial brief excitation followed by a period of inhibition and finally a prolonged excitation (Buford and Smith 1993; Prochazka et al. 1978; Wand et al. 1980). Kinematically, knee flexion and initial ankle extension is followed by ankle flexion that raises the foot to clear the obstacle. The same sensory stimulation delivered during stance often increases ipsilateral extensor activity (Buford and Smith 1993; Forssberg et al. 1977). The primary effect of the foot encountering an obstacle during stance is, however, an enhanced flexor activity during the subsequent swing phase (Buford and Smith 1993; Forssberg 1979). The increased extension facilitates propulsion (Forssberg 1979; Forssberg et al. 1977), and the pronounced flexion lifts the foot in anticipation of the obstruction during the next swing phase in this stumbling preventive reaction (Forssberg 1979).
The neuronal networks underlying the stumbling corrective and preventive reactions have not been identified. It is known that cutaneous afferents are important for evoking the reflex because stumbling correction is abolished by anesthesia of the skin of the foot (Forssberg et al. 1977; Wand et al. 1980) and can be evoked by puffs of air on the paw dorsum (Forssberg 1979). On the other hand, electrical stimulation of the skin has been reported to evoke some (Forssberg 1979) but not all (Buford and Smith 1993; Wand et al. 1980) features of stumbling correction, suggesting that participation of other sensory afferents is required to evoke full pattern of stumbling correction (discussed in Buford and Smith 1993).
These experiments began during a survey of the effects of stimulation of hindlimb peripheral nerves during fictive locomotion in decerebrate cats. It was noted that when the cutaneous nerve innervating the dorsum of the foot [superficial peroneal (SP)] is stimulated during the flexion phase, hip and knee flexor activity increased, and a brief period of ankle extensor activity was produced. This study attempts to determine the extent to which these actions resemble the stumbling corrective reaction described by others during real locomotion. This paper reports the patterns of motoneuron activity recorded in the peripheral nerves after stimulation of the SP nerve during fictive locomotion. The effects of SP nerve stimulation recorded intracellulary in hindlimb motoneurons are presented in the companion paper (Quevedo et al. 2005). Preliminary results have been presented (McCrea 2002; McCrea et al. 1998).
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
. Using halothane anesthesia delivered in a mixture of 70% NO2 and 30% O2, left hindlimb nerves were prepared for recording and stimulation. Remaining sciatic, obturator, and femoral nerve branches were cut in both hindlimbs, and tendons around the hip were sectioned bilaterally. A laminectomy exposed the L4–L7 segments of the spinal cord for intracellular recording from lumbar motoneurons. Those results are presented in the companion paper (Quevedo et al. 2005). The cat was transferred to a stereotaxic frame, and a precollicular–postmamillary decerebration was performed in which both cortices and all tissue rostral to the transection were removed. Anesthesia was discontinued, and the cat was paralyzed with gallamine triethiodide or pancuronium bromide and artificially ventilated.
Ipsilateral hindlimb nerves placed on bipolar electrodes for either stimulation or recording included combinations of posterior biceps (PB), semitendinosus (St), semimembranosus and anterior biceps (SmAB), medial gastrocnemius (MG), lateral gastrocnemius and soleus (LGS), plantaris (Plant), flexor digitorum longus (FDL), flexor hallucis longus (FHL), tibial (Tib), peroneus longus (PerL), TA, peroneous tertius and brevis, extensor digitorum longus (EDL), and SP nerves. Vasti, rectus femoris (separately or together as quadriceps, Q), and sartorius (Sart) were mounted in ventral cuff electrodes. In one experiment, Vas and rectus femoris were mounted together (Q), and the branches to medial and lateral sartorious (mSart and lSart) were separated. Branches of the psoas (Psoas) muscle nerve were dissected and mounted in two experiments. The adductor tendons of both hips were cut, and the right hindlimb was denervated by cutting the sciatic nerve and the nerves to SmAB and PBSt. In accord with the strong knee flexion that occurs during stumbling correction with the activity of PB and St (e.g., Pratt et al. 1996), these bifunctional (knee flexor, hip extensor) muscles will be referred to simply as knee flexors.
Fictive locomotion was elicited by unilateral or bilateral electrical stimulation of the mesencephalic locomotor region (MLR; 30–200 µA, 0.5- or 1.0-ms pulses, 15–20 Hz: see Guertin et al. 1995). Peripheral nerves were stimulated with 0.2-ms constant current stimulus pulses with intensities expressed in multiples of threshold (T) for the most excitable fibers as measured at the cord dorsum in L6 or L7. Trains of stimuli (9–45 shocks, typically 15; 200 Hz) were delivered to several cutaneous and muscle afferent nerves in each experiment to evoke stumbling correction and other reflexes during fictive locomotion. Rectified and integrated electroneurogram (ENG) activity was used to monitor fictive locomotor activity, and by means of a software-based window discriminator, to trigger stimulus delivery from a selected ENG at a particular phase of the step cycle. Trains were delivered every two or three cycles with intervening step cycles serving as control step cycles. Window discriminator trigger pulses were collected and used to construct off-line averages of ENG activity in steps with and without peripheral nerve stimulation. Latencies of changes in ENG amplitudes were measured from the arrival of the afferent volley at the spinal cord. The duration of the step cycle was defined as the time interval between the onset of consecutive burst activity in a selected nerve. Cycle durations were compared with a t-test (2 samples assuming equal variances, 
= 0.05). Rectified and integrated ENGs were digitized (500 Hz) and analyzed using software developed by the Winnipeg Spinal Cord Research Centre (Pentium PCs running Linux).
The effects of SP nerve stimulation were examined in 28 experiments in which brain stem–evoked fictive locomotion was produced. Once fictive locomotion was established, the effects of SP nerve stimulation were observed on ipsilateral hindlimb ENG activity. In those preparations displaying all features of stumbling correction (n = 14), the effects of SP nerve stimulation were examined further during multiple runs of fictive locomotion (typically of 2-min durations). These results are reported here and in the companion paper (Quevedo et al. 2005). Preparations not displaying fictive stumbling correction and some with stumbling correction were also used for other purposes (McCrea et al. 2000; Quevedo et al. 2000; unpublished observations).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Figure 1 shows rectified-integrated ENG recordings from selected hindlimb muscle nerves during MLR-induced fictive locomotion. Activity in a hip flexor ENG (Sart) was used to trigger a train of stimuli to the SP nerve every other step cycle with a delay of about 250 ms from the onset of flexor motoneuron activity. SP nerve stimulation produced a large burst of PB (knee flexor, hip extensor) and ankle extensor (LGS) activity and a delayed excitation of ankle flexors (TA). These bursts were bigger than those occurring during unperturbed step cycles. Averaged ENG activity (n = 5) occurring with (solid traces) and without SP stimulation (dotted) during a different run in the same experiment is shown in Fig. 2. Shortly after the beginning of the stimulus train there is 1) an increase in knee flexor (PB, St) ENG activity, 2) a burst of ankle (LGS) extensor activity, and 3) an inhibition of TA and PerL (ankle flexor) activity, followed by 4) ankle flexor excitation. Furthermore, there was 5) an increase in hip flexor (Sart) activity. The increased knee flexor activity, the excitation of ankle extensor motoneurons, and the inhibition followed by excitation of ankle flexor activity are characteristics of real stumbling correction (see Fig. 1 of Prochazka et al. 1978; Fig. 3 of Wand et al. 1980) as is the evoked activity in Sart (Pratt et al. 1996). The pattern of ENG activity in Fig. 1 (also Figs. 2, 3A, 4A, and 6A) shows the features of what we will call the fictive stumbling corrective reaction. These features were produced in all 14 preparations reported here.
|
|
|
|
|
), EDL activity is sometimes delayed from that of TA during fictive locomotion. In those cases, the degree of SP-evoked inhibition in EDL was difficult to assess (Fig. 2). Figure 3 shows averaged ENG activity obtained with (continuous lines) and without (dotted lines) SP stimulation delivered during the flexion phase of fictive locomotion. In Fig. 3A, there is an excitation of knee flexors and ankle extensors characteristic of fictive stumbling. The most common response in Sart (11/14 experiments) was an increase in activity soon after the onset of SP stimulation (Fig. 2). A similar response was observed in Psoas for the two times it was studied. The other response in the Sart motor pool (3 experiments) was an initial inhibition during SP stimulation that was followed by a large increase in activity (Fig. 3A). The records in Fig. 3B from the same preparation show that reducing the number of shocks in the stimulus train decreased the duration of the inhibition of ankle and hip flexor motoneurons. An excitation of hip and ankle flexors that follows or persists after the termination of SP stimulation is shown in Figs. 2, 3, A and B, 4A, and 6A.
Ankle extensor excitation was evoked by SP stimulation during flexion in all 14 preparations. This evoked activity was often larger than that occurring during the extensor phase of the fictive locomotor step cycle (e.g., Figs. 1, 2, and 4A). Unlike the activation of limb flexors, ankle extensor activity did not persist after the end of the stimulus train to the SP nerve. When recorded separately, excitation during stumbling correction was seen in the Plant, MG, and LGS nerves; the branches to lateral gastrocnemius and soleus were not separated.
Recruitment of other extensors during fictive stumbling correction was variable. In the hip extensors, SmAB, small bursts were evoked with SP stimulation during flexion in 2/14 experiments (Fig. 3A) and very small (almost undetectable) bursts (Fig. 4A) in 7 experiments. In one experiment, both rectus femoris and vastii motoneurons were recruited during stumbling correction (data not shown). In two experiments, no activity was evoked in the combined Q nerve (Fig. 4). FDL activity was often similar to that of TA and PerL in that there was usually a brief period of excitation followed by inhibition (Fig. 2). As stimulation of the SP nerve during flexion produced no effect on the FHL ENG (e.g., Fig. 2), it is assumed that the effects evoked on the flexor digitorum and hallucis longus (FDHL) nerve in Fig. 4 are caused by a recruitment of FDL motoneurons by SP stimulation (Degtyarenko et al. 1998). In some experiments, the response in FDHL was weak, and the period of inhibition was missing.
The latencies of the increases and decreases in ENG activity occurring during fictive stumbling correction are shown on the left of the respective traces in Fig. 2. Average latencies were calculated from runs in eight experiments in which all features of the stumbling reflex were observed and without an initial inhibition of Sart activity. The latency for the increase in both hip and knee flexor ENG activities was 4 ± 1 (SD) ms (n = 8). The latency of ankle extensor activation (16 ± 2 ms) was always greater than that of the flexor motoneurons acting at the hip or knee. The brief increase of ankle flexor activity that often preceded the prominent inhibition had an average latency of 5 ± 1 ms in these eight experiments. As mentioned, the period of inhibition of ankle flexors was variable (e.g., Fig. 3) but often similar to the duration of the stimulus train (Figs. 2 and 4A). The large increase in ankle flexor activity occurred soon after the termination of SP stimulation. The evoked activity in SmAB in Fig. 3A had a latency of 
4 ms.
Stumbling preventive reaction: SP nerve stimulation during extension
Figure 4B shows the effects of SP nerve stimulation delivered during the extension phase in one of the two experiments where responses were compared with those evoked during flexion (Fig. 4A). During extension (Fig. 4B), SP stimulation evoked short-latency increases in hip (SmAB), knee (Q), and ankle (GS) extensor activity as well as in the combined FDHL nerve. These bursts were also larger than those occurring during control steps. Activity was also evoked in PBSt but was of shorter duration than that occurring during stumbling correction (Fig. 4A) and shorter than the stimulus train duration. The latency of SP-evoked GS activation during extension was 4 ms. Large, short-latency activity was evoked in FDHL in both the flexion and extension phases of fictive locomotion.
A particularly striking feature of SP stimulation during extension was, however, its effects on the amplitude of hip (Sart), knee (PBSt), and ankle (TA, EDL) ENGs in the subsequent step cycle. These bursts (Fig. 4B, stars) were considerably larger than those occurring without SP nerve stimulation. This pattern of motoneuron activity observed during fictive locomotion resembles that occurring during the stumbling preventive reaction in chronic spinal (Forssberg 1979; Forssberg et al. 1975) and intact (Buford and Smith 1993) cats. Thus stimulation of the SP nerve during fictive locomotion in decerebrate cats evokes ipsilateral hindlimb motoneuron activity much like that occurring during both the stumbling corrective and preventive reflexes observed during real walking.
Effects of SP stimulation on step cycle timing
The overlaid averaged records in Fig. 2 show an example of fictive stumbling correction in which there was little effect on either the duration of flexor activity or the time of onset of the subsequent extension phase. In this case, the increase in hip and knee flexor motoneuron activities evoked by SP stimulation during flexion was not accompanied by changes in step cycle timing. In the example shown in Fig. 3A, however, SP stimulation increased the duration of ongoing flexor activity, delayed the subsequent extensor phase, and hence delayed the onset of the next step cycle (compare solid and dotted traces). Figure 3B shows the effects of decreasing the duration of SP stimulation from 105 (21 shocks) to 50 ms (11 shocks). The shorter duration train did not affect the onset time of the next step cycle (see TA and Sart records) and did not evoke the excitation of ankle (and in this case hip) extensors characteristic of stumbling correction. Both stimulus trains increased the amplitude of hip, knee, and ankle flexor activity. Figure 4A shows another example in which cycle duration was prolonged by SP stimulation during flexion. In this case, the stimulus train duration was relatively long with respect to the short step cycle period. Because the primary goal of this study was to mimic an obstacle striking the foot briefly during swing, the effects of altering the duration of SP stimulation on the timing of the step cycle were not systematically explored. It is clear, however, that SP stimulation can affect the timing of the step cycle. Presumably this is achieved by excitatory actions evoked through the flexor portion of the central pattern generating networks (Quevedo et al. 2005).
Figure 5 is taken from one experiment in which, during most runs, SP stimulation during the flexion phase evoked the characteristic stumbling correction pattern of brief ankle extensor activation and in ankle flexors, a period of inhibition followed by excitation (data not shown). In some runs, however, the response to SP nerve stimulation was variable. In the segment shown in Fig. 5A, the SP nerve was stimulated twice (15 shocks, 200 Hz, 2 T) during the flexion phase of fictive locomotion. The first stimulus presentation resulted in a rapid termination of flexion (note the truncated durations of bursts in the Sart and EDL ENGs) and the onset of extensor (LGS) activity. This is a resetting to, or a premature initiation of, extension (see also Fig. 6, D–F). The next SP stimulus train resulted in essentially the opposite effect. There was a large increase in the amplitude and duration of flexor (Sart and EDL) activity. Variable effects of SP stimulation in this experiment were also produced at higher stimulus intensity (5 T). This is shown in Fig. 5B, where the first SP stimulation shortens the ongoing flexion phase, whereas the second increases the amplitude and duration of flexor activity. In other trials, 5-T SP stimulation evoked no extensor activity but prolonged the flexion phase (data not shown). Thus in this experiment, SP stimulation produced seemingly at random, stumbling correction, a resetting to extension, or a flexion phase prolongation (Stecina et al. 2005).
|
Which afferents evoke the stumbling corrective reflex?
In this series of experiments, 2-T intensities of SP stimulation using trains typically of 15 shocks (200 Hz) were used to evoke the stumbling corrective reflex. As evident from the short latencies, the excitation of knee and sometimes hip flexors occurred with the first shock in the train. While systematic efforts were not made to determine minimum stimulus intensities or the effects of higher intensity stimulation, in one experiment, stimulation at 1.6 T evoked stumbling correction. This indicates that the large diameter cutaneous afferents in the SP nerve are sufficient for evoking these reflexes during fictive locomotion in denervated and paralyzed cats. To determine if other afferents from around the foot might contribute to stumbling correction, the effects of stimulation of several other nerves during the flexion phase of fictive locomotion were examined.
Figure 6, A–F, compares the effects of stimulation during flexion of the SP nerve, the nerves from the ankle flexors (EDL, PerL, TA), and an ankle extensor (MG) nerve. All panels except F were obtained in the same experiment. Stimulation of EDL or PerL at 5 T (an intensity sufficient to recruit group II afferents) increased hip and ankle flexor activity when either EDL or PerL nerves were stimulated (Fig. 6, B and C) (Stecina et al. 2005). The small, flat response in the LGS nerve in Fig. 6, B–D, is stimulus artifact made evident by the on-line rectification and integration.
Stimulation of the ankle flexor nerve, TA (Fig. 6D), cuts short ongoing Sart activity and produces prominent excitation of both ankle (LGS) and hip extensors (SmAB) before Sart activity occurs again. This is a resetting of the step cycle to extension (Perreault et al. 1995). A similar termination of ongoing flexion and initiation of a premature extensor phase is also seen after stimulation of an ankle extensor nerve (Fig. 5E, MG) or, in another experiment, of the mixed muscle and cutaneous plantar foot nerve (Fig. 6F; Tib) (Guertin et al. 1995). These results show that, while activation of EDL and PerL group II afferents might contribute to hip flexion, only stimulation of SP afferents is able to evoke the full pattern of stumbling correction.
Including the example shown, the stumbling correction evoked by SP stimulation was compared to the effects of TA stimulation in four experiments, EDL in five experiments, Tib in two experiments, and to stimulation of ankle extensors in three experiments. In all cases, only SP stimulation evoked stumbling correction. The effects of the other nerves were in keeping with the repertoire of effects shown in Fig. 6. In conclusion, in these preparations, only the cutaneous SP nerve (Fig. 6A) evoked ankle extensor activity and briefly silenced ankle flexor (TA) activity while exciting hip and knee flexors, i.e., evoked the stumbling corrective reflex.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
; Forssberg 1979; Prochazka et al. 1978; Wand et al. 1980) and in chronic spinal cats (Forssberg 1979; Forssberg et al. 1977) during real stumbling correction.
Functionally, stumbling correction during swing consists of knee flexion coupled with activation of ankle extensors and an initial inhibition of ankle flexors that assists in removing the paw from further contact with the obstacle. This is followed by a period of ankle flexion. During the swing phase of locomotion in adult cats, the latencies of knee flexor (St) activation during stumbling correction are 9.2–9.7 ms (Forssberg 1979) when evoked with electrical stimulation and 10 ms when evoked with mechanical stimulation (Forssberg 1979). Those latencies measured in the electromyogram include the afferent conduction times from the distal SP nerve and the efferent conduction to PBSt (3 + 2 ms) plus a delay at the neuromuscular junction (1 ms) for an estimated 6-ms delay. In these experiments, latencies were measured from the cord dorsum (no afferent delay) to the response in the ENG (efferent conduction time but no neuromuscular delay). Adding a 4-ms correction to these data to the 4-ms latency of increased PBSt ENG activity during fictive stumbling correction gives a value (8 ms) comparable with that reported during real stumbling correction (Forssberg 1979). Similarly, the mean 20-ms (16 + 4 ms correction) increase in ankle extensor ENG activity found here compares favorably with the mean 25-ms latency of ankle extensor activity using mechanical stimulation (Prochazka et al. 1978; Wand et al. 1980).
Stimulation of the SP nerve during the extension phase of fictive locomotion also produced actions similar to those occurring during real locomotion. This includes the increase in ongoing extensor muscle activity and the increase in flexor activity in the subsequent step cycle (Fig. 4B). Thus the effects of SP nerve simulation in decerebrate cats during fictive locomotion occur with a pattern and at latencies similar to those reported in awake animals during real stumbling corrective and preventive reactions.
Some of the variations in the reflex pattern reported during real stumbling correction were also encountered during fictive stumbling. For example, hip extensor EMG activity is often but not always a feature of the real stumbling reaction (Buford and Smith 1993). While strong SmAB activation was not a feature of fictive stumbling, activity was sometimes evoked in SmAB (Fig. 3A). The duration of flexor activity during the swing phase may be prolonged in real (Buford and Smith 1993) and fictive stumbling correction. Excitation of hip flexors (Sart and Psoas) is a prominent feature of fictive stumbling correction even when preceded by inhibition (Fig. 3). Kinematic analysis shows that there can be an increased flexion at the hip during real stumbling (Forssberg et al. 1977; Pratt et al. 1996; Wand et al. 1980). On the other hand, the powerful activation of the bifunctional PBSt (hip extensor, knee flexor) and the hip extensor, anterior biceps, muscles during real stumbling can produce extension or reduced flexion at the hip that may be absent in weaker stumbling reactions (Buford and Smith 1993). During stumbling correction in forward locomotion, there is an initial excitation of the unifunctional (knee and hip flexor) medial Sart, while the lateral Sart (knee extensor and hip flexor) is inhibited (Pratt et al. 1996). These differing actions may explain the mixture of effects recorded when the lateral and medial branches were combined (Sart) during fictive stumbling correction (Sart excitation in Fig. 2, initial inhibition in Fig. 3, and mixed initial effects in Fig. 4). The excitation of knee extensors that occurred in one of two experiments during fictive stumbling correction has not been reported during real stumbling correction and requires further study. The companion paper (Quevedo et al. 2005) reports the existence of very small, short-latency SP-evoked excitation in two Q motoneurons.
Effects of SP stimulation on the timing and amplitude of locomotor ENG bursts
SP stimulation evokes a net inhibition of ankle flexors that ends with the termination of stimulation. We suggest that the emergence of strong activity after the termination of the SP stimulus train is caused by an active excitation of flexor motoneurons and not by an escape from inhibition. The parsimonious explanation is that SP afferents access and can facilitate the operation of the central circuitry producing the locomotor excitation of flexors, i.e., the flexor portion of the central pattern generator for locomotion. After a mixture of stimulus-locked short-latency postsynaptic potentials in motoneurons during the stimulus train, this locomotor related excitation produces an enhancement of limb flexor activity. The finding that the duration of the flexion phase of the fictive step cycle is often increased during both fictive and real stumbling reactions (Buford and Smith 1993) is in keeping with this explanation. This interpretation is further strengthened by the excitation of the subsequent flexor phase that occurs during both fictive and real stumbling correction when stimulation occurs during stance.
The question arises as to whether the ankle extensor activity that is evoked during stumbling correction represents a premature initiation of the extension phase of the step cycle (i.e., a resetting). We consider this unlikely because 1) the activation of ankle extensors is rarely accompanied by strong activation of hip or knee extensors, 2) except for ankle flexors, other flexors are often active during the period of ankle extensor activity, and 3) the enhancement of flexor activity can occur without changes in the timing of the step cycle. We suggest in the companion study (Quevedo et al. 2005) that ankle extensor activation occurs by activation of specialized short-latency reflex pathways from SP afferents to ankle extensor motoneurons and not as a result of a brief resetting to a new extension phase of the step cycle.
It was possible to show reliable fictive stumbling correction in one-half of the preparations in this series of experiments (14/28). We have no adequate explanation for the failure to produce the activation of knee flexors and ankle extensors characteristic of stumbling correction in the others. The results in Fig. 5 suggest that excitatory SP pathways to both flexor and extensor portions of the locomotor pattern generator exist, but unknown mechanisms normally control the expression of the functionally appropriate response.
Is the stumbling corrective reaction a cutaneous reflex?
Our observations on the effects of stimulating other nerves around the foot (Fig. 6) and throughout the hindlimb (Guertin et al. 1995; McCrea 2001; Perreault et al. 1995; Stecina et al. 2005) have not identified any other nerve that can evoke the full sequence and pattern of motoneuron activation characteristic of fictive stumbling correction. We suggest that stumbling corrective reflexes during fictive locomotion are evoked mainly by activation of low threshold cutaneous afferents in the SP nerve. During real locomotion, electrical stimulation of the dorsal foot during flexion activates knee flexors but does not inhibit ankle flexors or evoke substantial ankle extensor activity (discussed in Buford and Smith 1993). Thus it has been argued that, in addition to cutaneous SP afferents, activation of other afferents is needed to produce stumbling correction (Buford and Smith 1993). During fictive locomotion, 75-ms trains of shocks (e.g., 15, 200-Hz pulses) to the SP nerve alone produced all the features of stumbling correction described in intact animals. We suggest that failure of electrical stimulation to evoke the full stumbling corrective reaction in intact preparations could result from the use of different stimulus parameters and often single shock stimulation used in those studies (Buford and Smith 1993; Forssberg 1979; Wand et al. 1980). The abolition of real stumbling correction after local anesthesia of the skin of the foot (Wand et al. 1980; see also Forssberg et al. 1975; 1977) is in keeping with the cutaneous nature of the stumbling corrective reflex. After anesthesia, mechanical stimuli produce only brief short-latency responses in ankle and knee flexors (Wand et al. 1980).
Even if cutaneous afferents can produce the complete pattern of stumbling correction, mechanical stimuli to the foot dorsum during a real swing phase would activate a variety of afferents in other nerves and could modify responses evoked by SP nerve activation. For example, activation of group II afferents from EDL and PerL muscles could contribute to hip and ankle flexion. One difficulty in assessing such potential contributions in our preparation is that, during fictive locomotion, stimulation of flexor afferents may sometimes evoke opposite reflex effects (McGrea et al. 2000). Presumably activation of group I ankle extensors and plantar foot afferents (Tib) during flexion would not contribute to stumbling correction since these nerves reset the step cycle to extension (Fig. 6F; Guertin et al. 1995).
The present and accompanying (Quevedo et al. 2005) results show that the adult decerebrate cat preparation can serve as a useful model of the stumbling corrective reactions described during real locomotion. It would be of great interest to characterize interneurons involved in SP reflex pathways that also access the rhythm generator and shape the output of the locomotor networks.
|
GRANTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
ACKNOWLEDGMENTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: D. A. McCrea, Spinal Cord Research Ctr., Univ. of Manitoba, 730 William Ave., Winnipeg, Manitoba R3E3J7, Canada (E-mail: dave{at}scrc.umanitoba.ca)
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Buford JA and Smith JL. Adaptive control for backward quadrupedal walking. III. Stumbling corrective reactions and cutaneous reflex sensitivity. J Neurophysiol 70: 1102–1114, 1993.
Degtyarenko AM, Simon ES, Norden-Krichmar T, and Burke RE. Modulation of oligosynaptic cutaneous and muscle afferent reflex pathways during fictive locomotion and scratching in the cat. J Neurophysiol 79: 447–463, 1998.
Eng JJ, Winter DA, and Patla AE. Strategies for recovery from a trip in early and late swing during human locomotion. Exp Brain Res 102: 339–349, 1994.[ISI][Medline]
Fleshman JW, Lev-Tov A, and Burke RE. Peripheral and central control of flexor digitorum longus and flexor hallucis longus motoneurons: the synaptic basis of functional diversity. Exp Brain Res 54: 133–149, 1984.[ISI][Medline]
Forssberg H. Stumbling corrective reaction: a phase-dependent compensatory reaction during locomotion. J Neurophysiol 42: 936–953, 1979.
Forssberg H, Grillner S, and Rossignol S. Phase dependent reflex reversal during walking in chronic spinal cats. Brain Res 85: 103–107, 1975.[CrossRef][ISI][Medline]
Forssberg H, Grillner S, and Rossignol S. Phasic gain control of reflexes from the dorsum of the paw during spinal locomotion. Brain Res 132: 121–139, 1977.[CrossRef][ISI][Medline]
Guertin P, Angel MJ, Perreault M-C, and McCrea DA. Ankle extensor group I afferents excite extensors throughout the hindlimb during MLR-evoked fictive locomotion in the cat. J Physiol 487: 197–209, 1995.[ISI][Medline]
Lam T, Wolstenholme C, van der Linden M, Pang MY, and Yang JF. Stumbling corrective responses during treadmill-elicited stepping in human infants. J Physiol 553: 319–331, 2003.
McCrea D, Stecina K, and Quevedo S. Flexor group II muscle afferents can enhance flexor activity during fictive locomotion. Soc Neurosci Abtr 460:02, 2000.
McCrea DA. Spinal circuitry of sensorimotor control of locomotion. J Physiol 533: 41–50, 2001.
McCrea DA. Neuronal pathways serving the stumbling reflex. Satellite Symposium 3rd Forum of European Neuroscience, Motor Control and Proprioception: Physiology, Pathology and Recovery, Paris, France, July 9–12, 2002.
McCrea DA, Quevedo J, Fedirchuk B, and Gosgnach S. The stumbling corrective reaction during fictive locomotion in the cat. In: Neuronal Mechanisms for Generating Locomotor Activity, edited by Kiehn O, Harris-Warrick RM, Jordan LM, and Kudo N. New York: The New York Academy of Sciences, 1998, p. 502–504.
McCrea DA, Stecina K, Quevedo J, and Gosgnach S. Flexor group II afferents can enhance flexor activity during fictive locomotion. Soc Neurosci Abstr 26: 1233, 2000.
Perreault M-C, Angel MJ, Guertin P, and McCrea DA. Effects of stimulation of hindlimb flexor group II muscle afferents during fictive locomotion. J Physiol 487: 211–220, 1995.[ISI][Medline]
Pratt CA, Buford JA, and Smith JL. Adaptive control for backward quadrupedal walking V. Mutable activation of bifunctional thigh muscles. J Neurophysiol 75: 832–842,1996.
Prochazka A, Sontag KH, and Wand P. Motor reactions to perturbations of gait: proprioceptive and somesthetic involvement. Neurosci Lett 7: 35–39, 1978.
Quevedo J, Fedirchuk B, Gosgnach S, and McCrea D. Group I disynaptic excitation of cat hindlimb flexor and bifunctional motoneurones during fictive locomotion. J Physiol 525: 549–564, 2000.
Quevedo J, Stecina K, and McCrea DA. Intracellular analysis of reflex pathways underlying the stumbling corrective reaction during fictive locomotion in the cat. J Neurophysiol 94: 2053–2062, 2005.
Schillings AM, Van Wezel BMH, and Duysens J. Mechanically induced stumbling during human treadmill walking. J Neurosci Methods 67: 11–17, 1996.[CrossRef][ISI][Medline]
Schmidt BJ, Meyers DE, Fleshman JW, Tokuriki M, and Burke RE. Phasic modulation of short latency cutaneous excitation in flexor digitorum longus motoneurones during fictive locomotion. Exp Brain Res 71: 568–578, 1988.[CrossRef][ISI][Medline]
Trank TV, Chen C, and Smith JL. Forms of forward quadrupedal locomotion. I. A comparison of posture, hindlimb kinematics, and motor patterns for normal and crouched walking. J Neurophysiol 76: 2316–2326, 1996.
Van Wezel BMH, Ottenhoff FAM, and Duysens J. Dynamic control of location-specific information in tactile cutaneous reflexes from the foot during human walking. J Neurosci 17: 3804–3814, 1997.
Wand P, Prochazka A, and Sontag KH. Neuromuscular responses to gait perturbations in freely moving cats. Exp Brain Res 38: 109–114, 1980.[ISI][Medline]
Zehr EP, Komiyama T, and Stein RB. Cutaneous reflexes during human gait: electromyographic and kinematic responses to electrical stimulation. J Neurophysiol 77: 3311–3325, 1997.
This article has been cited by other articles:
|
|
 |
|
  W. J. Kargo and S. F. Giszter Individual Premotor Drive Pulses, Not Time-Varying Synergies, Are the Units of Adjustment for Limb Trajectories Constructed in Spinal Cord J. Neurosci., March 5, 2008; 28(10): 2409 - 2425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Frigon and S. Rossignol Short-Latency Crossed Inhibitory Responses in Extensor Muscles During Locomotion in the Cat J Neurophysiol, February 1, 2008; 99(2): 989 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Balter and E. P. Zehr Neural Coupling Between the Arms and Legs During Rhythmic Locomotor-Like Cycling Movement J Neurophysiol, February 1, 2007; 97(2): 1809 - 1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. McVea and K. G. Pearson Long-Lasting, Context-Dependent Modification of Stepping in the Cat After Repeated Stumbling-Corrective Responses J Neurophysiol, January 1, 2007; 97(1): 659 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Rybak, K. Stecina, N. A. Shevtsova, and D. A. McCrea Modelling spinal circuitry involved in locomotor pattern generation: insights from the effects of afferent stimulation J. Physiol., December 1, 2006; 577(2): 641 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Boothe, A. H. Cohen, and T. W. Troyer Temporal Correlations in Stochastic Models of Double Bursting During Simulated Locomotion J Neurophysiol, March 1, 2006; 95(3): 1556 - 1570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Stecina, J. Quevedo, and D. A. McCrea Parallel reflex pathways from flexor muscle afferents evoking resetting and flexion enhancement during fictive locomotion and scratch in the cat J. Physiol., November 15, 2005; 569(1): 275 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Quevedo, K. Stecina, and D. A. McCrea Intracellular Analysis of Reflex Pathways Underlying the Stumbling Corrective Reaction During Fictive Locomotion in the Cat J Neurophysiol, September 1, 2005; 94(3): 2053 - 2062. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||
