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

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 of M cells 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 in M cells 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 caused M cells to burst phasically. M cells 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.