β-pompilidotoxin modulates spontaneous activity and persistent sodium currents in spinal networks

Area of Science:

• Neuroscience
• Computational Neuroscience
• Molecular Neuroscience

Background:

• Spinal cord rhythm generation mechanisms remain unclear.
• Intrinsic properties of interneurons and sodium currents (INaP, INaT) are implicated in network oscillations.

Purpose of the Study:

• Investigate the effect of beta-pompilidotoxin (β-PMTX) on spinal network rhythm generation.
• Elucidate β-PMTX's impact on sodium currents (INaP, INaT) and neuronal activity.

Main Methods:

• Intracellular recordings and multielectrode array (MEA) recordings in rat spinal cord cultures.
• Pharmacological manipulation including synaptic transmission blockade.
• Analysis of intrinsic neuronal activity and sodium current properties.

Main Results:

• β-PMTX reduced population bursts but increased asynchronous activity.
• Synaptically isolated networks showed increased intrinsic channel activity.
• β-PMTX converted silent interneurons to active ones and increased firing rates.
• The toxin affected INaT inactivation and increased INaP amplitude.

Conclusions:

• β-PMTX enhances intrinsic neuronal activity by modulating INaP and INaT.
• This modulation profoundly alters spontaneous rhythmic activity in spinal networks.
• β-PMTX offers a tool to study spinal network dynamics and sodium channel function.