Activity-dependent formation and location of voltage-gated sodium channel clusters at a CNS nerve terminal during postnatal development.
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 Navchannel 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 Navchannel clusters before and after hearing onset at postnatal day 12 in the rat and mouse auditory brain stem. In rats, the Navchannel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Navchannel cluster at the nodes was present before hearing onset. Initiation of heminodal Navchannel clustering was correlated with the expression of scaffolding protein ankyrinG and paranodal protein Caspr. However, in whirler mice with congenital deafness, heminodal Navchannels did not form clusters and maintained broad expression, but Navchannel clustering was normal at the nodes. In addition, a clear difference in the distance from the heminodal Navchannel 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 Navchannel 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.



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. Navchannel 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 Navchannels at the nerve terminal in the auditory brain stem.
The Department of Physiology, University of Texas Health Science Center, San Antonio, Texas; and.
Jie
J
Xu
The Department of Physiology, University of Texas Health Science Center, San Antonio, Texas; and.
Emmanuelle
E
Berret
The Department of Physiology, University of Texas Health Science Center, San Antonio, Texas; and kimjh@uthscsa.edu.|Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas.
Jun Hee
JH
Kim
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017487:Ankyrins / Q000378:metabolism; D064032:Calbindin 2 / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology* / Q000254:growth & development*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
C490614:Ank3 protein, rat; D017487:Ankyrins; D064032:Calbindin 2; D015816:Cell Adhesion Molecules, Neuronal; C105177:Cntnap1 protein, rat; D008565:Membrane Proteins; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D061566:Voltage-Gated Sodium Channels; C477218:Whrn protein, mouse
auditory; axon; calyx; central nervous system; channel; presynaptic terminal