Persistent sodium currents participate in fictive locomotion generation in neonatal mouse spinal cord

Guisheng Zhong, Mark A. Masino, Ronald M. Harris-Warrick

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

The persistent sodium current (INa(P)) has been implicated in the regulation of synaptic integration, intrinsic membrane properties, and rhythm generation inmanytypes of neurons. We characterized INa(P) in commissural interneurons (CINs) in the neonatal (postnatal days 0-3) mouse spinal cord; it is activated at subthreshold potentials, inactivates slowly, and can be blocked by low concentrations of riluzole. The role of INa(P) in locomotor pattern generation was examined by applying riluzole during fictive locomotion induced by NMDA, serotonin, and dopamine or by stimulation of the cauda equina. Blockade of INa(P) has marginal effects on the locomotion frequency but progressively weakens the rhythmic firing and locomotor-related membrane oscillation of CINs and motoneurons (MNs) and the locomotor-like bursts in ventral roots, until the motor pattern ceases. Riluzole directly affects the intrinsic firing properties of CINs and MNs, reducing their ability to fire repetitively during tonic depolarizations and raising their spike threshold. At the same time, riluzole has little effects on the strength of spike-evoked synaptic transmission onto CINs and MNs. Our results suggest that INa(P) is essential for the generation of the locomotor pattern and acts in part by regulating the frequency of interneuron firing in the central pattern generator for locomotion.

Original languageEnglish (US)
Pages (from-to)4507-4518
Number of pages12
JournalJournal of Neuroscience
Volume27
Issue number17
DOIs
StatePublished - Apr 25 2007

Keywords

  • Locomotion
  • Mouse
  • NMDA
  • Persistent sodium current
  • Riluzole
  • Spinal cord

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