No abstract

Reticulospinal (RS) neurons constitute the main descending motor system of lampreys. This study reports on natural conditions whereby N-methyl-D-aspartate (NMDA)-mediated plateau potentials were elicited and associated with the onset of locomotion. Reticulospinal neurons responded in a linear fashion to mild skin stimulation. With stronger stimuli, large depolarizing plateaus with spiking activity were elicited and were accompanied by swimming movements. Calcium imaging revealed sustained intracellular calcium rise upon sensory stimulation. Blocking NMDA receptors on RS neurons prevented the plateau potentials as well as the associated rise in intracellular calcium. Thus, the activation of NMDA receptors mediates a switch from sensory-reception mode to a motor command mode in RS neurons.

Serotonergic projections from raphe nuclei arrive in the lumbar enlargement of the spinal cord during the late fetal period in the rat, a time window during which the locomotor-related left/right and flexor/extensor coordinations switch from synchrony to alternation. The goal of the present study was to investigate the role played by serotonin (5-HT) in modulating the left/right and flexor/extensor alternations. Fictive locomotion was induced by bath application of N-methyl-D,L-aspartate (NMA) in the in vitro neonatal rat spinal cord preparation. By means of cross-correlation analysis we demonstrate that 5-HT, when added to NMA, improves left/right and flexor/extensor (recorded from the 3rd and 5th lumbar ventral roots, respectively) alternations. This effect was partly reproduced by activation of 5-HT(2A/2C) receptors. We then tested the contribution of endogenous 5-HT to NMA-induced fictive locomotion. Reducing the functional importance of endogenous 5-HT, either by inhibiting its synthesis with daily injections of p-chloro-phenylalanine (PCPA), starting on the day of birth, or by application of ketanserin (a 5-HT(2) receptor antagonist) or SB269970 (a 5-HT(7) receptor antagonist), disorganized the NMA-induced locomotor pattern. This pattern was restored in PCPA-treated animals by adding 5-HT to the bath. Blocking 5-HT(7) receptors disorganized the locomotor-like rhythm even in the absence of electrical activity in the brain stem, suggesting that NMA applied to the spinal cord does not cause 5-HT release by activating a spino-raphe-spinal loop. These results demonstrate that 5-HT is critical in improving the locomotor-related alternations in the neonatal rat.