Resurgent sodium current promotes action potential firing in the avian auditory brainstem

Abstract

Key points

• Auditory brainstem neurons of all vertebrates fire phase‐locked action potentials (APs) at high rates with remarkable fidelity, a process controlled by specialized anatomical and biophysical properties.

• This is especially true in the avian nucleus magnocellularis (NM) – the analogue of the mammalian anteroventral cochlear nucleus.

• In addition to high voltage‐activated potassium (K _HVA) channels, we report, using whole cell physiology and modelling, that resurgent sodium current ( I _NaR) of sodium channels (Na _V) is equally important and operates synergistically with K _HVA channels to enable rapid AP firing in NM.

• Anatomically, we detected strong Na _V1.6 expression near hearing maturation, which was less distinct during hearing development despite functional evidence of I _NaR, suggesting that multiple Na _V channel subtypes may contribute to I _NaR.

• We conclude that I _NaR plays an important role in regulating rapid AP firing for NM neurons, a property that may be evolutionarily conserved for functions related to similar avian and mammalian hearing.

Abstract

Auditory brainstem neurons are functionally primed to fire action potentials (APs) at markedly high rates in order to rapidly encode the acoustic information of sound. This specialization is critical for survival and the comprehension of behaviourally relevant communication functions, including sound localization and distinguishing speech from noise. Here, we investigated underlying ion channel mechanisms essential for high‐rate AP firing in neurons of the chicken nucleus magnocellularis (NM) – the avian analogue of bushy cells of the mammalian anteroventral cochlear nucleus. In addition to the established function of high voltage‐activated potassium channels, we found that resurgent sodium current ( I _NaR) plays a role in regulating rapid firing activity of late‐developing (embryonic (E) days 19–21) NM neurons. I _NaR of late‐developing NM neurons showed similar properties to mammalian neurons in that its unique mechanism of an ‘open channel block state’ facilitated the recovery and increased the availability of sodium (Na _V) channels after depolarization. Using a computational model of NM neurons, we demonstrated that removal of I _NaR reduced high‐rate AP firing. We found weak I _NaR during a prehearing period (E11–12), which transformed to resemble late‐developing I _NaR properties around hearing onset (E14–16). Anatomically, we detected strong Na _V1.6 expression near maturation, which became increasingly less distinct at hearing onset and prehearing periods, suggesting that multiple Na _V channel subtypes may contribute to I _NaR during development. We conclude that I _NaR plays an important role in regulating rapid AP firing for NM neurons, a property that may be evolutionarily conserved for functions related to similar avian and mammalian hearing.

Key points

• Auditory brainstem neurons of all vertebrates fire phase‐locked action potentials (APs) at high rates with remarkable fidelity, a process controlled by specialized anatomical and biophysical properties.

• This is especially true in the avian nucleus magnocellularis (NM) – the analogue of the mammalian anteroventral cochlear nucleus.

• In addition to high voltage‐activated potassium (K _HVA) channels, we report, using whole cell physiology and modelling, that resurgent sodium current ( I _NaR) of sodium channels (Na _V) is equally important and operates synergistically with K _HVA channels to enable rapid AP firing in NM.

• Anatomically, we detected strong Na _V1.6 expression near hearing maturation, which was less distinct during hearing development despite functional evidence of I _NaR, suggesting that multiple Na _V channel subtypes may contribute to I _NaR.

• We conclude that I _NaR plays an important role in regulating rapid AP firing for NM neurons, a property that may be evolutionarily conserved for functions related to similar avian and mammalian hearing.