INTERINSTITUTE LABORATORY OF NEUROMUSCULAR PLASTICITY

(Nencki Institute of Experimental Biology and Institute of Biocybernetics

and Biomedical Engineering)

| Head: Urszula SŁAWIŃSKA, Ph.D., D.Sc., E-mail: u.slawinska@nencki.gov.pl Prof. Emeritus Teresa GÓRSKA, Ph.D., D.Sc., Staff: Henryk MAJCZYŃSKI, Ph.D., Barbara CHOJNICKA, M.Sc. and staff employed by the Institute of Biocybernetics and Biomedical Engineering: Anna CABAJ, M.Sc., Katarzyna MALESZAK, M.Sc.

Our research is devoted to the investigation of the plasticity processes in the neuromuscular system in rats and the neural control of locomotion. Particularly the research involves the investigation of functional aspects of muscle recovery after central and peripheral nervous system injury in young as well as adult rats. Moreover, changes in the locomotor function after spinal lesions of different extent and supraspinal structures and the recovery of locomotor function in rats are investigated. The main interest is given to search for the new rehabilitation techniques that can stimulate the neuromuscular plasticity mechanisms responsible for restitution of muscle function (i.e. intra spinal neural transplantation, pharmacological treatment, intensive training and rehabilitation) after various nervous system injuries.

To present examples of our research, the results of several investigations carried out on adult and young rats to study plasticity of neuromuscular system in matured and immatured animals will be described.

In developing rats we demonstrated that neural circuitry in the spinal cord, although present, is not yet fully developed in neonatal animals (Exp. Neurology 2002). This was shown in experiments performed on developing rats (7-9 days old). In rat pups the hindlimb postural function is immature and the animals do not lift their pelvis off the ground. However exogenous L-DOPA administration (150 mg/kg) results in a marked increase in postural activity of extensor muscles and episodes of locomotion characterized by rhythmic reciprocal bursts of EMG activity in flexor and extensor muscles. Nevertheless, quantitative analysis of EMG burst characteristics indicated that the pattern of L-DOPA induced locomotion in immature rats resembles only in some respects that observed in adults during spontaneous locomotion. These results suggest that although the spinal neuronal circuits that generate locomotor movements are already present during the first week of life, but they are not yet fully functionally developed.

Our next set of experiments show that this immaturity might be crucial to observe functional readjustment of transposed extensor muscle into the bed of antagonistic flexor muscle (J. Neuroscience 2002). In animals operated as young, the pattern of transposed muscle activity recorded during locomotion was rearranged in line with new functional demands after transposition, although the “innate” soleus activity was still preserved. In contrast to the extensor-like activity of normal soleus, the transposed muscle was activated during the extension as well as the flexion of an ankle joint. In adult rats such surgery resulted in rearranged activity of transposed soleus muscle only in a few animals. We postulated that the immaturity of the nervous system at the moment of surgery might be crucial for this readjustment.

In the other set of experiments carried out on adult rats we demonstrated that after total spinal cord transection the transplantation of embryonic neurons containing serotonin into the spinal cord below the level of injury is able to influence its residual circuitry and improve the recovery of motor function of hindlimbs (Exp Brain Res 2000). In our study the grafting of embryonic neural tissue of raphe nuclei region was used in the hope that the grafted serotonergic cells will integrate with the host neuronal circuitry, establish appropriate connections and release the lacking serotonin directly into the spinal cord below the total transection. Our results provided evidence that the graft enhanced the recovery of hindlimb locomotor functions after complete spinal cord transection. Moreover our results demonstrated that transplantation of serotonergic cells was effective even if carried out a long time after spinal cord injury when the neuronal circuitry below the lesion was already reorganized and changes in the effectors, i.e. motoneurons and muscles, were well advanced.

Fig. 1. Locomotor-like hind limb movements induced by tail pinching in paraplegic rats 3 months after spinal cord transection: (A) paraplegic control rat, (B) paraplegic rat 2 months after intra spinal grafting of embryonic serotoninergic cells

Selected publications:

1. Górska T., Zmysłowski W., Majczyński H. 1999. Overground locomotion in intact rats: interlimb coordination, support patterns and support phases duration. Acta Neurobiol. Exp., 59: 131-144

2. Sławińska U., Majczyński H., Djavadian R. 2000. Recovery of hindlimb motor function after spinal cord transection is enhanced by grafts of the embryonic raphe nuclei. Exp. Brain Res., 132: 27-38.

3. Sławińska U., Kasicki S. 2002. Altered EMG activity pattern of rat soleus muscle transposed into the bed of antagonist muscle. J. Neurosci. 22(14): 5808-5812.

Reserch in cooperation with University College of London:

4. Tyč F., Sławińska U., Vrbová G. 1999. The age dependent effect of partial denervation of rat fast muscles on their activity. Acta Neurobiol. Exp., 59: 105-114.

5. Navarrete R., Sławińska U., Vrbová G. 2002. EMG activity patterns of hindlimb muscles during L-Dopa induced locomotion in neonatal rats. Exp. Neurol., 173: 256-265.

Research in cooperation with Göteborg University:

6. Jankowska E, Hammar I., Chojnicka B., Heden CH. 2000. Effects of monoamines on interneurons in four spinal reflex pathways from group I and/or group II muscle afferents. Eur. J. Neurosci., 12: 701-714

7. Hammar I.,Chojnicka B., Jankowska E. 2002. Modulation of responses of feline ventral spinocerebellar tract neurons by monoamines. J. Comp. Neurol., 443: 298-309

8. Hammar I, Sławińska U., Jankowska E. 2002. A comparison of post-activation depression of synaptic actions evoked by different afferents at different locations in the feline spinal cord. Exp. Brain Res., 145: 126-129.

9. Jankowska E., Sławińska U., Hammar I. 2002. Differential presynaptic inhibition in the dorsal horn and intermediate zone of feline spinal cord. J. Physiol. 542 (1): 287-299.

10. Jankowska E., Sławińska U., Hammar I. 2002. On organization of a neuronal network in pathways from group II muscle afferents in feline lumbar spinal segments
J. Physiol. 542 (1): 301-314.