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The role of serotonin in the control of locomotor movements and strategies for restoring locomotion after spinal cord injury

100%

Slawinska U., Miazga K., Jordan L. M.

Acta Neurobiologiae Experimentalis

2014

tom 74

nr 2

In this review we will discuss different ways for re-establishing serotonergic activity that can enhance recovery of coordinated plantar stepping after spinal cord injury in adult rats. It is well known that serotoninergic neurons located in the medulla are able to initiate locomotor activity. This effect is exerted by actions on motoneurons and on neurons of the locomotor CPG (Central Pattern Generator). Motoneuron and interneuron excitability is increased, and putative CPG interneurons display oscillatory behaviour in response to serotonin receptor activation. The medullary serotonergic nuclei play multiple roles in the control of locomotion, and they terminate on specific target neurons with different types of serotonergic receptors in the spinal cord. Activation of these serotonergic receptors can restore locomotor movements after spinal cord injury. Specifically, using defined serotonergic agonists the 5-HT2 receptors can be stimulated to control CPG activation as well as motoneuron output, while 5-HT7 receptors to control activity of the locomotor CPG. These results are consistent with the roles for these receptors during locomotion in intact rodents and in rodent brainstem-spinal cord in vitro preparations. The other possibility to encourage the remaining spinal cord circuitry below the total transection to control recovery of plantar hindlimb stepping is restoration of serotonergic innervation by intraspinal grafting of embryonic 5-HT neurons. Our data show that grafting of different populations of 5-HT neurons dissected from embryonic brainstem provides differential control over multiple components of the spinal locomotor circuitry through specific serotonin receptors. Moreover, we demonstrated that the best effect of motor recovery is obtained after grafting of neurons destined to form the B1, B2 and B3 descending 5-HT systems. Using only one of the subpopulations for intraspinal grafting, for example, B3 or the lateral group of 5-HT neurons, induces only partial recovery of plantar stepping with a clear lack of proper interlimb coordination. This confirms the hypothesis that transplantation of 5-HT neurons from specific embryonic sources is necessary to obtain optimal recovery of locomotor hindlimb movement.

Differential effects on locomotor-like movements of paraplegic rats produced by activation of 5-HT2 or 5-HT7 receptors

88%

Slawinska U., Miazga K., Majczynski H., Cabaj A. M., Jordan L. M.

Acta Neurobiologiae Experimentalis

2011

tom 71

nr S

There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT7 receptors leads to activation of the spinal cord circuitry for locomotion. Both types of receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used different agonists that are known to be efficient in promoting locomotor recovery in paraplegic rats: 8-OHDPAT (acting on 5-HT7) and quipazine (acting on 5-HT2 receptors). Motor performance was tested before and 15 – 30 min after i.p. drug application in spinal rats placed with the forequarters on a platform above a treadmill while the hindlimbs were touching the moving treadmill belt. Tail pinching was used to induce hindlimb movements that were monitored using video recordings synchronized with simultaneous EMG recordings from the soleus and tibialis anterior muscles of both legs. The application of either 5-HT receptor agonist improved hindlimb plantar walking. Analysis of intra- and interlimb coordination confirmed that the motor performance was significantly better, but in slightly different ways, after application of either drug. Interlimb coordination (left-right coordination) was significantly better after 8-OHDPAT, and the activity of antigravity soleus muscle was significantly longer during locomotor-like movement enhanced by quipazine (an improvement in intralimb coordination). Our results suggest that 5-HT2 and 5-HT7 receptors both facilitate activity in the spinal circuitry controlling locomotion, but their effects are likely exerted on different populations of spinal neurons. These agonists also have affinity to other types of receptors (e.g., 8-OHDPAT acts also on 5-HT1a receptors and quipazine also has affinity for 5-HT3 receptors), so further experiments are needed to substantiate the roles of 5-HT2a and 5-HT7 receptors.

Ograniczanie wyników

2 Acta Neurobiologiae Experimentalis

2 Jordan L. M.

2 Miazga K.

2 Slawinska U.

1 Cabaj A. M.

1 Majczynski H.

1 2014

1 2011

Wyniki wyszukiwania

The role of serotonin in the control of locomotor movements and strategies for restoring locomotion after spinal cord injury

Differential effects on locomotor-like movements of paraplegic rats produced by activation of 5-HT2 or 5-HT7 receptors