Department of Otolaryngology/Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and.
J Neurophysiol. 2013 Oct;110(8):1848-59. doi: 10.1152/jn.00151.2013. Epub 2013 Jul 31.
The principal inhibitory neurotransmitter in the mammalian cochlear nucleus (CN) is glycine. During age-related hearing loss (AHL), glycinergic inhibition becomes weaker in CN. However, it is unclear what aspects of glycinergic transmission are responsible for weaker inhibition with AHL. We examined glycinergic transmission onto bushy cells of the anteroventral CN in normal-hearing CBA/CaJ mice and in DBA/2J mice, a strain that exhibits an early onset AHL. Glycinergic synaptic transmission was examined in brain slices of mice at 10-15 postnatal days old, 20-35 days old, and at 6-7 mo old. Spontaneous inhibitory postsynaptic current (sIPSC) event frequency and amplitude were the same among all three ages in both strains of mice. However, the amplitudes of IPSCs evoked (eIPSC) from stimulating the dorsal CN were smaller, and the failure rate was higher, with increasing age due to decreased quantal content in both mouse strains, independent of hearing status. The coefficient of variation of the eIPSC amplitude also increased with age. The decay time constant (τ) of sIPSCs and eIPSCs were constant in CBA/CaJ mice at all ages, but were significantly slower in DBA/2J mice at postnatal days 20-35, following the onset of AHL, and not at earlier or later ages. Our results suggest that glycinergic inhibition at the synapses onto bushy cells becomes weaker and less reliable with age through changes in release. However, the hearing loss in DBA/2J mice is accompanied by a transiently enhanced inhibition, which could disrupt the balance of excitation and inhibition.
在哺乳动物耳蜗核（CN）中，主要的抑制性神经递质是甘氨酸。在与年龄相关的听力损失（AHL）中，CN 中的甘氨酸抑制作用减弱。然而，尚不清楚 AHL 导致甘氨酸能抑制作用减弱的具体方面。我们研究了正常听力的 CBA/CaJ 小鼠和 DBA/2J 小鼠（一种表现出早期 AHL 的品系）的前腹耳蜗核中的篮状细胞的甘氨酸能传递。在 10-15 日龄、20-35 日龄和 6-7 月龄的小鼠脑片中检查了甘氨酸能突触传递。在两种小鼠品系中，所有三个年龄段的自发性抑制性突触后电流（sIPSC）事件频率和幅度均相同。然而，由于两种小鼠品系的量子含量减少，刺激背侧 CN 诱发的 IPSC（eIPSC）幅度减小，失败率增加，与听力状态无关。eIPSC 幅度的变异系数也随年龄增加而增加。sIPSC 和 eIPSC 的衰减时间常数（τ）在 CBA/CaJ 小鼠的所有年龄段均保持不变，但在 DBA/2J 小鼠中，在 AHL 发生后，即 20-35 日龄时，明显变慢，而在更早或更晚的年龄则不会。我们的结果表明，随着年龄的增长，篮状细胞上的甘氨酸能抑制作用通过释放变化而减弱和变得不可靠。然而，DBA/2J 小鼠的听力损失伴随着暂时增强的抑制作用，这可能会破坏兴奋和抑制之间的平衡。
