With the development of neural prostheses, neural plasticity including synaptic remodeling under electrical stimulation is drawing more and more attention. Indeed, intracochlear electrical stimulation used to restore hearing in deaf can induce the loss of residual hearing and synapses of the inner hair cells (IHCs). However, the mechanism under this process is largely unknown. Considering that the guinea pig is always a suitable and convenient choice for the animal model of cochlea implant (CI), in the present study, normal-hearing guinea pigs were implanted with CIs. Four-hour electrical stimulation with the intensity of 6 dB above electrically evoked compound action potential (ECAP) threshold (which can decrease the quantity of IHC synapses and the excitability of the auditory nerve) resulted in the upregulation of Bdnf (p < 0.0001) and downregulation of Nt-3 (p < 0.05). Intracochlear perfusion of exogenous NT-3 or TrkC/Fc (which blocks NT-3) can, respectively, resist or aggravate the synaptic loss induced by electrical stimulation. In contrast, local delivery of exogenous BDNF or TrkB/Fc (which blocks BDNF) to the cochlea, respectively, exacerbated or protected against the synaptic loss caused by electrical stimulation. Notably, the synaptic changes were only observed in the basal and middle halves of the cochlea. All the findings above suggested that NT-3 and BDNF may play opposite roles in the remodeling of IHC synapses induced by intracochlear electrical stimulation, i.e. NT-3 and BDNF promoted the regeneration and degeneration of IHC synapses, respectively.

随着神经假体的发展，包括电刺激下的突触重塑在内的神经可塑性越来越受到关注。事实上，用于恢复聋人听力的耳蜗内电刺激会导致内毛细胞 (IHC) 的残余听力和突触丧失。然而，这个过程的机制在很大程度上是未知的。考虑到豚鼠一直是人工耳蜗（CI）动物模型的合适和方便的选择，在本研究中，在正常听力的豚鼠中植入了人工耳蜗。强度高于电诱发复合动作电位 (ECAP) 阈值 6 dB 的 4 小时电刺激（可降低 IHC 突触的数量和听神经的兴奋性）导致Bdnf的上调( p  < 0.0001) 和Nt-3的下调( p  < 0.05)。外源性 NT-3 或 TrkC/Fc（阻断 NT-3）的耳蜗内灌注可分别抵抗或加重电刺激引起的突触损失。相比之下，外源性 BDNF 或 TrkB/Fc（阻断 BDNF）分别局部递送至耳蜗会加剧或防止电刺激引起的突触损失。值得注意的是，突触变化仅在耳蜗的基底和中半部分观察到。以上结果表明NT-3和BDNF可能在耳蜗内电刺激诱导的IHC突触重构中起相反的作用，即NT-3和BDNF分别促进了IHC突触的再生和退化。