Wang Yong, Manis Paul B
1115 Bioinformatics Bldg, CB#7070, Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina 27599-7070, USA.
J Neurophysiol. 2005 Sep;94(3):1814-24. doi: 10.1152/jn.00374.2005. Epub 2005 May 18.
Age-related hearing loss (AHL) typically starts from high-frequency regions of the cochlea and over time invades lower-frequency regions. During this progressive hearing loss, sound-evoked activity in spiral ganglion cells is reduced. DBA mice have an early onset of AHL. In this study, we examined synaptic transmission at the endbulb of Held synapse between auditory nerve fibers and bushy cells in the anterior ventral cochlear nucleus (AVCN). Synaptic transmission in hearing-impaired high-frequency areas of the AVCN was altered in old DBA mice. The spontaneous miniature excitatory postsynaptic current (mEPSC) frequency was substantially reduced (about 60%), and mEPSCs were significantly slower (about 115%) and smaller (about 70%) in high-frequency regions of old (average age 45 days) DBA mice compared with tonotopically matched regions of young (average age 22 days) DBA mice. Moreover, synaptic release probability was about 30% higher in high-frequency regions of young DBA than that in old DBA mice. Auditory nerve-evoked EPSCs showed less rectification in old DBA mice, suggesting recruitment of GluR2 subunits into the AMPA receptor complex. No similar age-related changes in synaptic release or EPSCs were found in age-matched, normal hearing young and old CBA mice. Taken together, our results suggest that auditory nerve activity plays a critical role in maintaining normal synaptic function at the endbulb of Held synapse after the onset of hearing. Auditory nerve activity regulates both presynaptic (release probability) and postsynaptic (receptor composition and kinetics) function at the endbulb synapse after the onset of hearing.
年龄相关性听力损失（AHL）通常始于耳蜗的高频区域，并随着时间的推移侵入低频区域。在这种进行性听力损失过程中，螺旋神经节细胞中声音诱发的活动会减少。DBA小鼠存在AHL的早发情况。在本研究中，我们检测了听觉神经纤维与前腹侧耳蜗核（AVCN）中的毛细胞之间的Held终扣处的突触传递。老年DBA小鼠AVCN听力受损的高频区域中的突触传递发生了改变。与年轻（平均年龄22天）DBA小鼠的音调匹配区域相比，老年（平均年龄45天）DBA小鼠高频区域的自发微小兴奋性突触后电流（mEPSC）频率大幅降低（约60%），mEPSC明显更慢（约115%）且更小（约70%）。此外，年轻DBA小鼠高频区域的突触释放概率比老年DBA小鼠高约30%。老年DBA小鼠中听觉神经诱发的EPSC的整流作用较小，这表明AMPA受体复合物中招募了GluR2亚基。在年龄匹配、听力正常的年轻和老年CBA小鼠中未发现类似的与年龄相关的突触释放或EPSC变化。综上所述，我们的结果表明，听觉神经活动在听力开始后维持Held终扣处正常突触功能方面起着关键作用。听力开始后，听觉神经活动调节Held终扣突触处的突触前（释放概率）和突触后（受体组成和动力学）功能。
