Burst firing in motoneurons represents the basis for generating meaningful movements. Neuromodulators and inhibitory receptor blockers cocktails have been used for years to induce burst firing in vitro; however, the ionic mechanisms in the motoneuron membrane which contribute to burst initiation and amplitude modulation are not fully understood. Small conductance Ca2+-activated potassium channels (SK channels) regulate excitatory inputs and firing output of motoneurons and interneurons and, therefore, are a candidate for mediating bursting behavior. The present study examines the role of SK channels in the generation of synchronized bursting using an in vitro spinal cord preparation from adult mice. Our results show that SK channel inhibition is required for both initiation and amplitude modulation of burst firing. Specifically, administration of the synaptic inhibition blockers strychnine and picrotoxin amplified the spinal circuit excitatory drive but not enough to evoke bursting. However, when SK channels were inhibited using various approaches, the excitatory drive was further amplified and synchronized bursting was always evoked. Also, graded SK channel inhibition modulated the amplitude of the burst in a dose-dependent manner, which was reversed using SK channel activators. Importantly, modulation of neuronal excitability using multiple approaches failed to mimic the effects of SK modulators, suggesting a specific role for SK channel inhibition in generating bursting. Both NMDA and AMPA receptors were found to drive the synchronized bursts. Blocking gap junctions did not disturb the burst synchrony. These results demonstrate a novel mechanistic role for SK channels in initiating and modulating burst firing of spinal motoneurons.
- spinal motoneurons
- SK channels
- synchronized bursting
- motor output
- Copyright © 2016, Journal of Neurophysiology