Activation of locomotion in adult chronic spinal rats is achieved by transplantation of embryonic raphe cells reinnervating a precise lumbar level

Traumatic lesions of the spinal cord yield a loss of supraspinal control of voluntary locomotor activity, although the spinal cord contains the necess ary circuitry to generate the basic locomotor pattern. In spinal rats, this network, known as central pattern generator (CPG), was shown to be sensiti ve to serotonergic pharmacological stimulation. In previous works we have s hown that embryonic raphe cells transplanted into the sublesional cord of a dult rats can reinnervate specific targets, restore the lesion-induced incr ease in receptor densities of neurotransmitters, promote hindlimb weight su pport, and trigger a locomotor activity on a treadmill without any other ph armacological treatment or training. With the aim of discriminating whether the action of serotonin on CPG is as sociated to a specific level of the cord, we have transplanted embryonic ra phe cells at two different levels of the sublesional cord (T9 and T11) and then performed analysis of the kinematic and EMG activity synchronously rec orded during locomotion. Locomotor performances were correlated to the rein nervated level of the cord and compared to that of intact and transected no ntransplanted animals. The movements expressed by T11 transplanted animals correspond to a well defined locomotor pattern comparable to that of the in tact animals. On the contrary, T9 transplanted animals developed limited an d disorganized movements as those of nontransplanted animals. The correlati on of the locomotor performances with the level of reinnervation of the spi nal cord suggests that serotonergic reinnervation of the L1-L2 level consti tutes a key element in the genesis of this locomotor rhythmic activity. Thi s is the first in vivo demonstration that transplanted embryonic raphe cell s reinnervating a specific level of the cord activate a locomotor behavior.