Synaptic transmission between end bulbs of Held and bushy cells in the cochlear nucleus of mice with a mutation in Otoferlin.
Mice that carry a mutation in a calcium binding domain of Otoferlin, the putative calcium sensor at hair cell synapses, have normal distortion product otoacoustic emissions (DPOAEs), but auditory brain stem responses (ABRs) are absent. In mutant mice mechanotransduction is normal but transmission of acoustic information to the auditory pathway is blocked even before the onset of hearing. The cross-sectional area of the auditory nerve of mutant mice is reduced by 54%, and the volume of ventral cochlear nuclei is reduced by 46% relative to hearing control mice. While the tonotopic organization was not detectably changed in mutant mice, the axons to end bulbs of Held and the end bulbs themselves were smaller. In mutant mice bushy cells in the anteroventral cochlear nucleus (aVCN) have the electrophysiological hallmarks of control cells. Spontaneous miniature excitatory postsynaptic currents (EPSCs) occur with similar frequencies and have similar shapes in deaf as in hearing animals, but they are 24% larger in deaf mice. Bushy cells in deaf mutant mice are contacted by ∼2.6 auditory nerve fibers compared with ∼2.0 in hearing control mice. Furthermore, each fiber delivers more synaptic current, on average 4.8 nA compared with 3.4 nA, in deaf versus hearing control mice. The quantal content of evoked EPSCs is not different between mutant and control mice; the increase in synaptic current delivered in mutant mice is accounted for by the increased response to the size of the quanta. Although responses to shocks presented at long intervals are larger in mutant mice, they depress more rapidly than in hearing control mice.
['Wright|Samantha|S|', 'Hwang|Youngdeok|Y|', 'Oertel|Donata|D|']
D000818:Animals D003056:Cochlear Nerve D017626:Cochlear Nucleus D003638:Deafness D004558:Electric Stimulation D016057:Evoked Potentials, Auditory, Brain Stem D005260:Female D006309:Hearing D008297:Male D008564:Membrane Potentials D008565:Membrane Proteins D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009474:Neurons D017354:Point Mutation D009435:Synaptic Transmission
cochlear nucleus Otoferlin electrophysiology excitatory postsynaptic currents mouse