N-methyl-D-aspartate receptor-induced inherent oscillatory activity in neurons active during fictive locomotion in the lamprey

摘要

Bath application of N-methyl-aspartate induces fictive locomotor activity in the isolated spinal cord preparation of the lamprey, as well as TTX-resistant membrane potential oscillations in many individual neurons. This inherent oscillatory activity is shown to depend on a specific activation of N-methyl-D-aspartate (NMDA) receptors. This activation initiates voltage-dependent, magnesium- requiring membrane potential bistability, presumably due to a development of a region of negative slope conductance in the current- voltage relation of the neuron. When sodium ions were removed from the bathing solution, oscillations disappeared, and the membrane potential was maintained at a hyperpolarized level, suggesting that the depolarizing current during the oscillatory cycle is mainly carried by sodium ions. Replacing Ca2+ with Ba2+ also leads to a cessation of oscillatory activity, with the membrane potential remaining at the more depolarized level. This indicates an involvement of a Ca2+-dependent K+ current during the repolarization phase. These findings, together with the voltage dependence, can account for the main characteristics of the NMDA receptor-induced, TTX-resistant membrane potential oscillations. This oscillatory behavior has been demonstrated in motoneurons and in several interneurons including CC interneurons but has not been found in edge cells, dorsal cells, or lateral interneurons. The possibility that inherent oscillatory membrane properties may contribute to the activity pattern during fictive locomotion was investigated in experiments with intracellular current injection in the absence of TTX. The stimulation effects obtained required the presence of magnesium ions and were analogous to the stimulation effects seen during oscillations after TTX blockade. Together with similarities in, for instance, frequency and amplitude between the locomotor oscillatory activity and the TTX-resistant oscillations, the results are compatible with an involvement of inherent, oscillatory membrane properties during fictive locomotion in the lamprey spinal cord.