The Persistent Sodium Current Generates Pacemaker Activities in the Central Pattern Generator for Locomotion and Regulates the Locomotor Rhythm

J Neurosci. 2008 Aug 20;28(34):8577-89. doi: 10.1523/JNEUROSCI.1437-08.2008.

Abstract

Rhythm generation in neuronal networks relies on synaptic interactions and pacemaker properties. Little is known about the contribution of the latter mechanisms to the integrated network activity underlying locomotion in mammals. We tested the hypothesis that the persistent sodium current (I(NaP)) is critical in generating locomotion in neonatal rodents using both slice and isolated spinal cord preparations. After removing extracellular calcium, 75% of interneurons in the area of the central pattern generator (CPG) for locomotion exhibited bursting properties and I(NaP) was concomitantly upregulated. Putative CPG interneurons such as commissural and Hb9 interneurons also expressed I(NaP)-dependent (riluzole-sensitive) bursting properties. Most bursting cells exhibited a pacemaker-like behavior (i.e., burst frequency increased with depolarizing currents). Veratridine upregulated I(NaP), induced riluzole-sensitive bursting properties, and slowed down the locomotor rhythm. This study provides evidence that I(NaP) generates pacemaker activities in CPG interneurons and contributes to the regulation of the locomotor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Clocks / drug effects
  • Biological Clocks / physiology*
  • Calcium / metabolism
  • Electrophysiology
  • Extracellular Space / metabolism
  • Fluorescent Dyes
  • Green Fluorescent Proteins / genetics
  • Homeodomain Proteins / genetics
  • In Vitro Techniques
  • Interneurons / physiology
  • Locomotion / physiology*
  • Mice
  • Mice, Transgenic
  • Periodicity*
  • Rats
  • Rats, Wistar
  • Sodium Channels / drug effects
  • Sodium Channels / physiology*
  • Spinal Cord / cytology
  • Spinal Cord / physiology*
  • Veratridine / pharmacology

Substances

  • Fluorescent Dyes
  • Homeodomain Proteins
  • Sodium Channels
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Veratridine
  • Calcium