LAUSR

In auditory pathways, the precision of action potential (AP) propagation depends on axon myelination and high densities of voltage-gated Na (Nav) channels clustered at nodes of Ranvier. Changes in Nav channel expression at the heminode, the final node before the nerve terminal, can alter AP invasion into the presynaptic terminal. We studied the activity-dependent formation of Nav channel clusters before and after hearing onset at postnatal day 12 in the rat and mouse auditory brain stem. In rats, the Nav channel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Nav channel cluster at the nodes was present before hearing onset. Initiation of heminodal Nav channel clustering was correlated with the expression of scaffolding protein ankyrinG and paranodal protein Caspr. However, in whirler mice with congenital deafness, heminodal Nav channels did not form clusters and maintained broad expression, but Nav channel clustering was normal at the nodes. In addition, a clear difference in the distance from the heminodal Nav channel to the calyx across the mediolateral axis of the medial nucleus of the trapezoid body (MNTB) developed after hearing onset. In the medial MNTB, where neurons respond best to high-frequency sounds, the heminodal Nav channel cluster was located closer to the terminal than in the lateral MNTB, where neurons respond best to low-frequency sounds. Thus sound-mediated neuronal activities are potentially associated with the refinement of the heminode adjacent to the presynaptic terminal in the auditory brain stem. NEW & NOTEWORTHY Clustering of voltage-gated sodium (Nav) channels and their distribution along the axon, specifically at the unmyelinated axon segment next to the nerve terminal, are essential for tuning propagated action potentials. Nav channel clusters near the nerve terminal and their location as a function of neuronal position along the mediolateral axis are controlled by auditory inputs after hearing onset. Thus sound-mediated neuronal activity influences the tonotopic organization of Nav channels at the nerve terminal in the auditory brain stem.