Resurgent Na+ currents promote ultrafast spiking in projection neurons that drive fine motor control

Benjamin M Zemel,Alexander A Nevue,Claudio V Mello,Peter V Lovell,Andre Dagostin,Henrique Von Gersdorff

doi:10.1038/s41467-021-26521-3

Benjamin M Zemel, Alexander A Nevue + Show 4 more

Open Access

https://doi.org/10.1038/s41467-021-26521-3

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Abstract

The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display robust high-frequency firing, ultra-narrow spike waveforms, superfast Na+ current inactivation kinetics, and large resurgent Na+ currents (INaR). These properties of songbird pallial motor neurons closely resemble those of specialized large pyramidal neurons in mammalian primary motor cortex. They emerge during the early phases of song development in males, but not females, coinciding with a complete switch of Na+ channel subunit expression from Navβ3 to Navβ4. Dynamic clamping and dialysis of Navβ4’s C-terminal peptide into juvenile RA neurons provide evidence that Navβ4, and its associated INaR, promote neuronal excitability. We thus propose that INaR modulates the excitability of upper motor neurons that are required for the execution of fine motor skills.

Highlights

The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood
Whole-cell current-clamp recordings (CC) performed in adult male zebra finch brain slices revealed that RA projection neurons (RAPNs) fire spontaneously in the absence of synaptic input
Song production in the zebra finch requires fast and precise signaling from RAPNs to activate and suppress syringeal musculature[31]

Summary

Introduction

The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. We report that projection neurons in the adult zebra finch song nucleus RA display robust high-frequency firing, ultra-narrow spike waveforms, superfast Na+ current inactivation kinetics, and large resurgent Na+ currents (INaR) These properties of songbird pallial motor neurons closely resemble those of specialized large pyramidal neurons in mammalian primary motor cortex. Nerve firing rates of >75 Hz are required for force summation in the superfast syrinx muscles[33] This high spike frequency in RAPNs during song production is energetically demanding as indicated by increased staining for cytochrome C in maturing males, but not female zebra finches[34]. Highfrequency firing electrocytes with extremely narrow AP spikes coexpress fast activating voltage-gated Na+(Nav) and K+ (Kv) channels[37,38]

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