Teresa Górska

Different patterns of fore-hindlimb coordination during overground locomotion in cats with ventral and lateral spinal lesions.

The effect of large, low thoracic (T10–T11), partial spinal lesions involving the ventral quadrants of the spinal cord and, to a different extent, the dorsolateral funiculi, on fore-hindlimb coordination was examined in cats walking overground at moderate speeds (40–100 cm/s). Three different forms of impairment of fore-hindlimb coordination depending on the extent of the lesions, were observed. Lesions sparing the dorsolateral or the ventral funiculus on one side preserved the equality of the fore- and hindlimb locomotor rhythms but changed the coupling between the movements of both girdles as compared to intact animals. Larger lesions in which, in addition to the ventral quadrants of the spinal cord, also major parts of the dorsolateral funiculi were destroyed elicited episodes of rhythm oscillations in both girdles, which appeared at the background of a small difference in these rhythms. Lesions destroying almost the whole spinal cord induced a permanent difference (about 200 ms) in the step cycle duration of the fore- and the hindlimbs. However, even in these animals some remnant form of fore-hindlimb coordination was found. The results suggest that dorsolateral funiculi play a major role in preserving the equality of rhythms in the foreand the hindlimbs, while lesions of the ventral quadrants change the coupling between limbs.

Unrestrained walking in cats with partial spinal lesions.

In four cats with partial spinal lesions, performed at a low thoracic level, involving ventral quadrants and, to a different extent, the dorsolateral funiculi, several parameters of locomotion were analyzed during unrestrained walking at moderate speed (0.3-1.0 m/s). Special attention was paid to the analysis of support patterns and the durations of support phases in step cycles. The operated subjects displayed a much greater variability of support patterns than intact cats as well as changes in the relative duration of some support phases. The most striking difference was an increase in the relative duration of support on two homolateral limbs accompanied by a reduction of support on diagonal limbs. These changes were mainly due to an impairment of fore-hindlimb coordination as shown by an increase in the phase shifts between the movements of diagonal limbs. Other parameters of locomotion were essentially unaltered, except for cats in which the lesion destroyed bilaterally major portions of the dorsolateral funiculi.

Unrestrained walking in intact cats

In five freely moving cats walking with speeds of 0.4-1.0 m/s several parameters of locomotion were investigated. Special attention was paid to the analysis of support patterns and the duration of support phases. The animals used almost exclusively (in 88 to 99% of steps) the 3-2-3-2-3-2-3-2 support pattern in which phases of support on three limbs alternated with phases of support on two limbs, homolateral and diagonal. The relative duration of support phases showed a tendency to decrease with increased locomotor velocity, except for the supports on diagonal limbs which slightly increased. The mean duration of the majority of support phases was similar and ranged between 12.2 and 14.5% of the step cycle. Phases of support on both hind- and one forelimb were somewhat (about 5%) shorter. It is concluded that the relative stability of support patterns and of the duration of support phases during walking observed in the present experiment may serve as a template for comparing changes in the gait produced by various CNS lesions.

Unrestrained walking in cats with medial pontine reticular lesions

The early postoperative effects of lesions, aimed to destroy the caudal pole of the nucleus reticularis pontis oralis (NRPO) and the rostral pole of the nucleus reticularis pontis caudalis (NRPC), were tested in freely moving cats, walking at moderate speed (0.4-1.0 m/s). In cats in which these structures were partly or completely destroyed, the main effect of lesions was an impairment of fore-hindlimb coordination, as shown by a change in the relationships between the lateral and diagonal time shift durations and the step cycle duration. In the second week after the surgery the values of the slopes of linear regressions relating these variables were markedly changed as compared to the preoperative data. The results suggest that the NRPO and NRPC are involved in maintaining the proper forehindlimb coordination during unrestrained locomotion in cats.

Comparison of two methods for quantitative assessment of unrestrained locomotion in the rat

Changes in locomotor movements induced by central and peripheral nerve injury or obtained as a result of pharmacological treatment are increasingly being investigated in rats. Several methods have been used to assess changes in the main locomotor indices, most of which are based on video recordings, usually with low time resolution, or on X-ray cinematographic recordings. Other methods are based on qualitative visual locomotor scoring systems like the BBB scale. We have analyzed locomotor indices in freely moving rats using two methods that can give quantitative results and which may be readily automated. One is based on detecting the onsets of swing and stance phases with contact electrodes (CE), while the second is based on recording the bursts of electromyographic activity (EMG) from the flexor and extensor muscles of each limb during the swing and stance phases, respectively. Besides the investigation of spontaneous locomotion in intact rats, our study also included an examination of locomotion on a ladder using EMG recording and analysis of locomotor disturbances following spinal cord hemisection, for which combined application of the two methods appeared to be useful. Overall, the EMG method appears to be more versatile than the CE method, although the use of both methods in parallel is recommended.

Changes in contractile properties of motor units of the rat medial gastrocnemius muscle after spinal cord transection

The effects of complete transection of the spinal cord at the level of Th9/10 on contractile properties of the motor units (MUs) in the rat medial gastrocnemius (MG) muscle were investigated. Our results indicate that 1 month after injury the contraction time (time‐to‐peak) and half‐relaxation time were prolonged and the maximal tetanic force in most of the MUs in the MG muscle of spinal rats was reduced. The resistance to fatigue also decreased in most of the MUs in the MG of spinal animals. Moreover, the post‐tetanic potentiation of twitches in MUs diminished after spinal cord transection. Criteria for the division of MUs into three types, namely slow (S), fast fatigue resistant (FR) and fast fatigable (FF), applied in intact animals, could not be directly used in spinal animals owing to changes in contractile properties of MUs. The ‘sag’ phenomenon observed in unfused tetani of fast units in intact animals essentially disappeared in spinal rats and it was only detected in few units, at low frequencies of stimulation only. Therefore, the MUs in spinal rats were classified as fast or slow on the basis of an adjusted borderline of 20 ms, instead of 18 ms as in intact animals, owing to a slightly longer contraction time of those fast motor units with the ‘sag’. We conclude that all basic contractile properties of rat motor units in the medial gastrocnemius muscle are significantly changed 1 month after complete spinal cord transection, with the majority of motor units being more fatigable and slower than those of intact rats.

Intrathecal administration of yohimbine impairs locomotion in intact rats

The effects of upper lumbar level intrathecal injection of yohimbine, an alpha2-noradrenergic antagonist, on overground locomotion in intact rats was studied. This treatment caused dose-dependent impairment of hindlimb locomotor movement, which varied from transient hindlimb paralysis at a dose of 200 microg/20 microl to transient trunk instability at 50 microg/20 microl. Repetitive (every 48 h) injections of yohimbine at high (200 microg/20 microl) and medium (100 microg/20 microl) doses caused tachyphylaxis, which usually led to a lack of reaction to the third injection. This phenomenon was not observed after repetitive injections of the low (50 microg/20 microl) dose of the drug. These results show that the noradrenergic system is involved in the control of locomotion, since intrathecal administration of a specific antagonist affects this activity in intact rats.

Changes in forelimb-hindlimb coordination after partial spinal lesions of different extent in the rat.

Forelimb-hindlimb coordination in adult rats moving freely along 2m long runway was investigated using the method of footprint recording. Rats were divided into 3 groups with different extent of spinal lesions (T(9)). Before surgery rats moved with a mean locomotor speed of 73±20 to 96±18cms(-1), stride lengths of 17.5±2.0 to 21.2±2.0cm, and trot like coordination. Early after surgery the locomotor speed and the stride lengths were decreased. The forelimb steps were shorter than hindlimb steps, which led to the occurrence of unpaired forelimb steps. Unpaired steps occurred when the hind paw print lay more than half the hindlimb stride length in front of the ipsilateral paw. The number of unpaired steps was negatively correlated with the difference between the fore- and hindlimb step lengths. The recovery of locomotor speed, stride length, and step sequence patterns took up to 3.5 months depending on the extent of lesion. In the last testings the coordination was characterized by increased distances between ipsilateral footprints leading to a change from an almost synchronized trot to a lesion-dependent walk. This change was accompanied by a switch from the use of both patterns A and C to the most frequent use of the Aa pattern that is better adapted to maintain the body balance. All locomotor changes depended on the extent of the injury of lateral and ventral funiculi. These results demonstrate that footprint analysis can be used for the evaluation of forelimb-hindlimb coordination after spinal lesion in rats.

Recovery of overground locomotion following partial spinal lesions of different extent in the rat

In six rats with incomplete low thoracic spinal cord lesions of different extent, basic gait indices such as locomotor speed, step cycle duration, soleus (Sol) muscle activity duration, the interval between the onsets of Sol and tibialis anterior (TA) muscle activities and interlimb coordination were investigated by EMG analysis of the Sol and TA muscles recorded using chronic electrodes. The operated animals were divided into two subgroups: (1) those with a smaller lesion involving the dorsal quadrants of the spinal cord and, to a variable extent, the ventrolateral funiculi, and (2) those with an extensive lesion sparing only parts of the ventral funiculi. The locomotion of all rats was tested once a week for the first 5 weeks postsurgery and then once or twice a month, up to 3.5 months. The surgical lesions affected all analyzed gait indices: the locomotor speed decreased, while all other indices increased compared to recordings made preoperatively. In both subgroups the major improvement in locomotion occurred within the first 5 weeks following surgery and the rats reached a plateau in their recovery at around 2 months postoperatively. The late effects of injury depended on the severity of the spinal lesion: in the subgroup of rats with a smaller lesion, the postoperative changes in the different indices amounted to approximately 20%, while in the subgroup with extensive lesions this was increased by 20-50%, with changes in various indices being strongly correlated with the extent of the injury in individual animals. These postoperative changes were partly due to alterations in the relationships between the analyzed variables.

Intrathecal application of cyproheptadine impairs locomotion in intact rats

In intact adult rats, cyproheptadine, a 5-HT2 antagonist, administered intrathecally at the midlumbar segments was found to impair hindlimb locomotor movements during overground locomotion. These effects were dose-dependent; they varied from transient complete hindlimb paraplegia seen at doses of 300 microg/20 microl, to short-lasting trunk instability at doses of 100 microg/20 microl. After the return of overground locomotion, transient abduction of one of the hindlimbs was observed in some animals. These findings demonstrate that the blockade of 5-HT2 receptors affects locomotion in intact rats. Our results provide support for the hypothesis of serotonergic involvement in rat locomotion, which, so far, has been based mainly on the effects of 5-HT2 agonists on the recovery of locomotion in spinal rats.