Developmental Profile of Ion Channel Specializations in the Avian Nucleus Magnocellularis

Abstract

Ultrafast and temporally precise action potentials (APs) are biophysical specializations of auditory brainstem neurons; properties necessary for encoding sound localization and communication cues. Fundamental to these specializations are voltage dependent potassium (KV) and sodium (NaV) ion channels. Here, we characterized the functional development of these ion channels and quantified how they shape AP properties in the avian cochlear nucleus magnocellularis (NM). We report that late developing NM neurons (embryonic [E] days 19–21) generate fast APs that reliably phase lock to sinusoidal inputs at 75 Hz. In contrast, early developing neurons (<E12) have slower and less reliable APs that preferentially fire to lower frequencies (5–10 Hz). With development, the membrane time constant of NM neurons became faster, while input resistance and capacitance decreased. Change in input resistance was due to a 2-fold increase in KV current from E10 to E21 and when high-voltage activated potassium (K+HVA) channels were blocked, APs for all ages became significantly slower. This was most evident for early developing neurons where the ratio of K+HVA current accounted for ~85% of the total KV response. This ratio dropped to ~50% for late developing neurons, suggesting a developmental upregulation of low-voltage activated potassium (K+LVA) channels. Indeed, blockade of K+LVA eliminated remaining current and increased neural excitability for late developing neurons. We also report developmental changes in the amplitude, kinetics and voltage dependence of NaV currents. For early developing neurons, increase in NaV current amplitude was due to channel density while channel conductance dominated for late developing neurons. From E10 to E21, NaV channel currents became faster but differed in their voltage dependence; early developing neurons (<E16) had similar NaV channel inactivation voltages while late developing NM neurons (>E19) contained NaV channels that inactivate at more negative voltages, suggesting alterations in NaV channel subtypes. Taken together, our results indicate that the refinement of passive and active ion channel properties operate differentially in order to develop fast and reliable APs in the avian NM.

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

“…; Hong et al . ). Based on previous findings, we hypothesized that K v 3‐containing channels play a major role in regulating the rapid firing capability NM neurons.…”

“…Our previous study recorded APs at near‐physiological temperature (∼35°C) and we showed a significant improvement of AP kinetics for NM neurons (Hong et al . ). For example, AP half‐width was reduced by ∼30% and fall rate increased by ∼40% when increasing the temperature to ∼35°C.…”

“…; Hong et al . ). Briefly, embryos were rapidly decapitated and the brain was dissected from the skull to isolate the brainstem region of interest.…”

“…For NM neurons at E11–12, however, individual square pulse width was extended to 5 ms, because neurons at this age are presented with significantly wider AP half‐width (average = 4.6 ms) than the other two age groups (Hong et al . ). In addition, square pulse trains were applied at different frequencies: 10, 30, 50, 70, 100, 120 and 150 Hz.…”

Distinct Neural Properties in the Low-Frequency Region of the Chicken Cochlear Nucleus Magnocellularis

“…D , Population data showing the number of APs elicited as a function of current injections from 0 to 200 pA, steps of 20 pA. NMc1/NMc2 neurons are divided into three subgroups: neurons displaying voltage responses similar to the neurons shown in A , B , and C are noted as A-like, B-like, and C-like, respectively (see Results for objective classification details). Mid- to high-frequency NM neurons (M-HF) are also shown as a reference (data modified from Hong et al, 2016). E , F , Population data showing resting membrane potential (RMP, E ) and input resistance ( F ) of A-like, B-like, and C-like NMc1/NMc2 neurons.…”