Low Somatic Sodium Conductance Enhances Action Potential Precision in Time-Coding Auditory Neurons.

Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear how gNa influences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs. BCs play a central role in both relaying and refining precise timing information from the auditory nerve, whereas SCs discard precise timing information and encode the envelope of sound amplitude. Nucleated-patch recording at near-physiological temperature indicated that the Na current density was 62% lower in BCs, and the voltage dependence of gNa inactivation was 13 mV hyperpolarized compared with SCs. We endowed BCs with SC-like gNa using two-electrode dynamic clamp and found that synaptic activity at physiologically relevant rates elicited APs with significantly lower probability, through increased activation of delayed rectifier channels. In addition, for two near-simultaneous synaptic inputs, the window of coincidence detection widened significantly with increasing gNa, indicating that refinement of temporal information by BCs is degraded by gNa Thus, reduced somatic gNa appears to be an adaption for enhancing fidelity and precision in time-coding neurons. SIGNIFICANCE STATEMENT: Proper hearing depends on analyzing temporal aspects of sounds with high precision. Auditory neurons that specialize in precise temporal information have a suite of unusual intrinsic properties, including nonovershooting action potentials and few sodium channels in the soma. However, it was not clear how low sodium channel availability in the soma influenced the temporal precision of action potentials initiated in the axon initial segment. We studied this using dynamic clamp to mimic sodium channels in the soma, which yielded normal, overshooting action potentials. Increasing somatic sodium conductance had major negative consequences: synaptic activity evoked action potentials with lower fidelity, and the precision of coincidence detection was degraded. Thus, low somatic sodium channel availability appears to enhance fidelity and temporal precision.

High-speed dynamic-clamp interface.

The dynamic-clamp technique is highly useful for mimicking synaptic or voltage-gated conductances. However, its use remains rare in part because there are few systems, and they can be expensive and difficult for less-experienced programmers to implement. Furthermore, some conductances (such as sodium channels) can be quite rapid or may have complex voltage sensitivity, so high speeds are necessary. To address these issues, we have developed a new interface that uses a common personal computer platform with National Instruments data acquisition and WaveMetrics IGOR to provide a simple user interface. This dynamic clamp implements leak and linear synaptic conductances as well as a voltage-dependent synaptic conductance and kinetic channel conductances based on Hodgkin-Huxley or Markov models. The speed of the system can be assayed using a testing mode, and currently speeds of >100 kHz (10 µs per cycle) are achievable with short latency and little jitter.