Persistent Sodium Current Drives Excitability of Immature Renshaw Cells in Early Embryonic Spinal Networks

Area of Science:

• Neuroscience
• Developmental Biology
• Spinal Cord Research

Background:

• Spinal cord (SC) spontaneous network activity (SNA) precedes sensory and descending inputs.
• SNA is characterized by giant depolarizing potentials (GDPs), often driven by GABA release from interneurons.
• The role of specific interneurons and their intrinsic properties in early SNA remains unclear.

Purpose of the Study:

• To investigate the activity of embryonic Renshaw cells (V1R) at the onset of SNA in the mouse embryonic SC.
• To determine if V1R are GABAergic and contribute to SNA.
• To identify intrinsic currents controlling V1R activity and their impact on SNA.

Main Methods:

• Intracellular recordings from embryonic mouse V1R at E12.5.
• Analysis of V1R synaptic and extrasynaptic GABA release.
• Pharmacological manipulation using riluzole to block persistent sodium currents (INaP).

Main Results:

• Embryonic V1R are GABAergic and form synaptic/extrasynaptic contacts with motoneurons.
• V1R exhibit spontaneous activity patterns, including repetitive-spiking and plateau potentials dependent on INaP.
• Blockade of INaP by riluzole altered SNA, reducing episode duration and increasing inter-episode intervals.

Conclusions:

• Persistent sodium currents (INaP) are present in the embryonic SC and control V1R excitability.
• INaP plays a crucial role in patterning early SNA in the developing mammalian spinal cord.
• This finding highlights a novel mechanism for the development of locomotor networks.