Coordinated expression of two types of low-threshold K+ channels establishes unique single spiking of mauthner cells among segmentally homologous neurons in the zebrafish hindbrain

Abstract

Expression of different ion channels permits homologously-generated neurons to acquire different types of excitability and thus code various kinds of input information. Mauthner (M) series neurons in the teleost hindbrain consist ofMcells and their morphological homologs, which are repeated in adjacent segments and share auditory inputs. When excited, M cells generate a single spike at the onset of abrupt stimuli, while their homologs encode input intensity with firing frequency. Our previous study in zebrafish showed that immature M cells burst phasically at 2 d postfertilization (dpf) and acquire single spiking at 4 dpf by specific expression of auxiliary Kvβ2 subunits inMcells in association with common expression of Kv1.1 channels in the M series. Here, we further reveal the ionic mechanisms underlying this functional differentiation. Pharmacological blocking of Kv7/KCNQ in addition to Kv1 altered mature M cells to fire tonically, similar to the homologs. In contrast, blocking either channel alone causedMcells to burst phasically.Mcells at 2 dpf fired tonically after blocking Kv7. In situ hybridization revealed specific Kv7.4/KCNQ4 expression in M cells at 2 dpf. Kv7.4 and Kv1.1 channels expressed in Xenopus oocytes exhibited low-threshold outward currents with slow and fast rise times, while coexpression of Kvβ2 accelerated and increased Kv1.1 currents, respectively. Computational models, modified from a mouse cochlear neuron model, demonstrated that Kv7.4 channels suppress repetitive firing to produce spike-frequency adaptation, while Kvβ2-associated Kv1.1 channels increase firing threshold and decrease the onset latency of spiking. Altogether, coordinated expression of these low-threshold K+ channels with Kvβ2 functionally differentiates M cells among homologous neurons.