EN
Serotoninergic neurons projecting from the brainstem to the spinal cord are engaged in initiation and control of the locomotor movements. This effect is exerted by actions on motoneurons as well as on the spinal cord neuronal network for locomotion, the Central Pattern Generator (CPG). The serotonergic neurons send their axons to specific neuronal target in the spinal cord where the different types of serotonergic receptors allow the serotonergic system to play multiple roles in the control of locomotion. Using defined serotonergic agonists and antagonists we demonstrated in intact and in paraplegic adult rats that the 5-HT2 receptors control CPG activation as well as motoneuron output, while 5-HT7 receptors activate the locomotor CPG and control interneurons responsible for intra-and interlimb coordination. The combined use of agonists of the 5-HT2 and 5-HT7 receptors in a low dose, that is not effective when applied by either drug alone, results in production of wellcoordinated weight supported locomotion with a reduced need for exteroceptive stimulation. Next we found that in adult paraplegic rats intraspinal grafting of different populations of 5-HT neurons dissected from embryonic brainstem can activate the spinal cord circuitry below the total transection and enhance recovery of plantar hindlimb stepping. However, the locomotor recovery differed depending on the source of the grafted cells. The best effect of motor recovery was obtained using a combination of B1, B2 and B3 serotonergic neurons for grafting. In addition, we confirmed using defined serotonergic antagonists that the action of reestablished serotonergic innervation responsible for locomotor recovery is mediated by 5-HT2 and 5-HT7 receptors, as it is in the normal condition of himdlimb locomotor control. Our investigations demonstrate the marked potential of the remaining spinal cord circuitry below the total transection to enhance recovery of plantar hindlimb stepping in paraplegic adult rats.