KCNQ5 reaches synaptic endings in the auditory brainstem at hearing onset and targeting maintenance is activity-dependent

Abstract

Kv7.5/KCNQ5, a voltage-dependent potassium channel that generates a subthreshold K+ current (also called M-current), is localized in excitatory endings of auditory brainstem nuclei in the adult rat. Here, we focus on how specific targeting develops from birth to adulthood in the rat. We first analyzed by immunocytochemistry the distribution of KCNQ5 during postnatal development of neurons in the anteroventral cochlear nucleus (AVCN) and their targets in the medial nucleus of the trapezoid body (MNTB). From postnatal days (P) 0 to 12, KCNQ5 immunoreactivity was restricted to cell bodies, whereas from P13 onward a shift in labeling pattern was seen, with KCNQ5 immunoreactivity becoming confined to synaptic endings in both the AVCN and MNTB. The developmental synaptic targeting was also accompanied by a downregulation of KCNQ5 transcripts in the cochlear nucleus from P13 onward, as seen with quantitative reverse transcriptase polymerase chain reaction. We further tested whether auditory nerve activity at hearing onset (approximately P12) regulates synaptic targeting of the channel. Cochleae were removed at P10, before hearing onset. In the MNTB, 3 days after cochlear ablation, at P13, KCNQ5 immunoreactivity was seen in calyces of Held, as in normal age-matched controls. However, immunolabeling virtually disappeared from MNTB calyces 40 days after cochlear ablation but reappeared in the somata of neurons in AVCN. These findings suggest that synaptic targeting of KCNQ5 in brainstem auditory neurons occurs around the time of hearing onset, regardless of auditory nerve activity. However, long-term synaptic localization after hearing onset depends on peripheral input.