Title: Glycinergic Synaptic Transmission in the Cochlear Nucleus of Mice with Normal Hearing and Age- 1 Related Hearing Loss 2

24 The principal inhibitory neurotransmitter in the mammalian cochlear nucleus (CN) is glycine. During 25 age-related hearing loss (AHL), glycinergic inhibition becomes weaker in CN. However, it is unclear what 26 aspects of glycinergic transmission are responsible for weaker inhibition with AHL. We examined 27 glycinergic transmission onto bushy cells of the anteroventral CN in normal hearing CBA/CaJ mice and in 28 DBA/2J mice, a strain that exhibits an early onset AHL. Glycinergic synaptic transmission was examined 29 in brain slices of mice at 10-15 postnatal days old, 20-35 days old, and at 6 7 months old. Spontaneous 30 inhibitory postsynaptic current (sIPSC) event frequency and amplitude were the same among all three 31 ages in both strains of mice. However, the amplitudes of IPSCs evoked (eIPSC) from stimulating the 32 dorsal CN were smaller, and the failure rate was higher, with increasing age due to decreased quantal 33 content in both mouse strains, independent of hearing status. The coefficient of variation of the eIPSC 34 amplitude also increased with age. The decay time constants of sIPSCs and eIPSCs were constant in 35 CBA/CaJ mice at all ages, but were significantly slower in DBA/2J mice at p20-35, following the onset of 36 AHL, and not at earlier or later ages. Our results suggest that glycinergic inhibition at the synapses onto 37 bushy cells becomes weaker and less reliable with age through changes in release. However, the 38 hearing loss in DBA/2J mice is accompanied by a transiently enhanced inhibition, which could disrupt the 39 balance of excitation and inhibition. 40