Wang Yong, Manis Paul B
Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, 1115 Bioinformatics Building, CB#7070, Chapel Hill, NC 27599-7070, USA.
J Assoc Res Otolaryngol. 2006 Dec;7(4):412-24. doi: 10.1007/s10162-006-0052-9. Epub 2006 Oct 26.
The bushy cells of the anterior ventral cochlear nucleus (AVCN) preserve or improve the temporal coding of sound information arriving from auditory nerve fibers (ANF). The critical cellular mechanisms entailed in this process include the specialized nerve terminals, the endbulbs of Held, and the membrane conductance configuration of the bushy cell. In one strain of mice (DBA/2J), an early-onset hearing loss can cause a reduction in neurotransmitter release probability, and a smaller and slower spontaneous miniature excitatory postsynaptic current (EPSC) at the endbulb synapse. In the present study, by using a brain slice preparation, we tested the hypothesis that these changes in synaptic transmission would degrade the transmission of timing information from the ANF to the AVCN bushy neuron. We show that the electrical excitability of bushy cells in hearing-impaired old DBA mice was different from that in young, normal-hearing DBA mice. We found an increase in the action potential (AP) firing threshold with current injection; a larger AP afterhyperpolarization; and an increase in the number of spikes produced by large depolarizing currents. We also tested the temporal precision of bushy cell responses to high-frequency stimulation of the ANF. The standard deviation of spikes (spike jitter) produced by ANF-evoked excitatory postsynaptic potentials (EPSPs) was largely unaffected in old DBA mice. However, spike entrainment during a 100-Hz volley of EPSPs was significantly reduced. This was not a limitation of the ability of bushy cells to fire APs at this stimulus frequency, because entrainment to trains of current pulses was unaffected. Moreover, the decrease in entrainment is not attributable to increased synaptic depression. Surprisingly, the spike latency was 0.46 ms shorter in old DBA mice, and was apparently attributable to a faster conduction velocity, since the evoked excitatory postsynaptic current (EPSC) latency was shorter in old DBA mice as well. We also tested the contribution of the low-voltage-activated K+ conductance (g (KLV)) on the spike latency by using dynamic clamp. Alteration in g (KLV) had little effect on the spike latency. To test whether these changes in DBA mice were simply a result of continued postnatal maturation, we repeated the experiments in CBA mice, a strain that shows normal hearing thresholds through this age range. CBA mice exhibited no reduction in entrainment or increased spike jitter with age. We conclude that the ability of AVCN bushy neurons to reliably follow ANF EPSPs is compromised in a frequency-dependent fashion in hearing-impaired mice. This effect can be best explained by an increase in spike threshold.
前腹侧蜗神经核（AVCN）的浓密细胞保留或改善了来自听神经纤维（ANF）的声音信息的时间编码。这一过程中涉及的关键细胞机制包括特殊的神经末梢、 Held终球以及浓密细胞的膜电导配置。在一种小鼠品系（DBA/2J）中，早发性听力损失会导致神经递质释放概率降低，以及Held终球突触处自发微小兴奋性突触后电流（EPSC）变小且变慢。在本研究中，我们使用脑片制备技术，检验了以下假设：突触传递的这些变化会降低从ANF到AVCN浓密神经元的时间信息传递。我们发现，听力受损的老年DBA小鼠中浓密细胞的电兴奋性与年轻的听力正常的DBA小鼠不同。我们发现，随着电流注入，动作电位（AP）发放阈值升高；AP后超极化增大；大的去极化电流产生的尖峰数量增加。我们还测试了浓密细胞对ANF高频刺激反应的时间精度。在老年DBA小鼠中，ANF诱发的兴奋性突触后电位（EPSP）产生的尖峰标准差（尖峰抖动）基本未受影响。然而，在100Hz的EPSP群集期间，尖峰同步化显著降低。这并非是浓密细胞在此刺激频率下发放AP能力的限制，因为对电流脉冲序列的同步化未受影响。此外，同步化的降低并非归因于突触抑制增强。令人惊讶的是，老年DBA小鼠的尖峰潜伏期缩短了０.46毫秒，这显然归因于传导速度更快，因为老年DBA小鼠中诱发的兴奋性突触后电流（EPSC）潜伏期也较短。我们还使用动态钳技术测试了低电压激活的K+电导（g (KLV)）对尖峰潜伏期的影响。g (KLV)的改变对尖峰潜伏期影响很小。为了测试DBA小鼠中的这些变化是否仅仅是出生后持续成熟的结果，我们在CBA小鼠中重复了实验，CBA小鼠在这个年龄范围内听力阈值正常。随着年龄增长，CBA小鼠未出现同步化降低或尖峰抖动增加的情况。我们得出结论，在听力受损的小鼠中，AVCN浓密神经元可靠跟随ANF EPSP的能力以频率依赖的方式受到损害。这种效应可以用尖峰阈值升高来最好地解释。
