5HT induces NMDA receptor-mediated intrinsic oscillations in embryonic amphibian spinal neurons

The existence and possible contribution of intrinsic membrane potential oscillations to the generation of locomotor rhythmicity was investigated in spinal cord neurons of newly hatched Rana temporaria tadpoles, by intracellular recording from immobilized animals. The bath application of 100 μM N-methyl-D-aspartate (NMDA) evoked continuous swimming-like activity in ventral motor roots and rhythmic synaptic drive to ventrally located spinal neurons, presumed to be motorneurons. In 0.5 μM tetrodotoxin-treated preparations, similar applications of NMDA depolarized neurons by ca. 20 mV, but did not lead to intrinsic oscillatory activity, although some evidence for voltage-dependent membrane bistability was obtained. However, bath application of the neuromodulatory amine, serotonin (5HT; 5 μM), in the presence of NMDA and TTX, reversibly induced sustained membrane potential oscillations (up to 40 mV in amplitude) that were similar in waveform to those already described in other adult vertebrate motor systems. The TTX-resistant oscillations were dependent upon the presence of magnesium ions in the bathing solution and were abolished by the NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV). The results suggest that in this simple, developing vertebrate locomotor system, the activation of 5HT receptors on spinal cord neurons in turn modulates NMDA receptor activation to enable the expression of intrinsic oscillatory membrane properties which could contribute to the generation of locomotor behaviour.