Multiple forms of homeostasis influence synaptic function under diverse activity conditions. Both presynaptic and postsynaptic forms of homeostasis are important, but their relative impact on fidelity is unknown. To address this issue, we studied auditory nerve synapses onto bushy cells in the cochlear nucleus of mice of both sexes. These synapses undergo bidirectional presynaptic and postsynaptic homeostatic changes with increased and decreased acoustic stimulation. We found that both young and mature synapses exhibit similar activity-dependent changes in short-term depression. Experiments using chelators and imaging both indicated that presynaptic Ca²⁺ influx decreased after noise exposure, and increased after ligating the ear canal. By contrast, Ca²⁺ cooperativity was unaffected. Experiments using specific antagonists suggest that occlusion leads to changes in the Ca²⁺ channel subtypes driving neurotransmitter release. Furthermore, dynamic-clamp experiments revealed that spike fidelity primarily depended on changes in presynaptic depression, with some contribution from changes in postsynaptic intrinsic properties. These experiments indicate that presynaptic Ca²⁺ influx is homeostatically regulated in vivo to enhance synaptic fidelity.

SIGNIFICANCE STATEMENT Homeostatic mechanisms in synapses maintain stable function in the face of different levels of activity. Both juvenile and mature auditory nerve synapses onto bushy cells modify short-term depression in different acoustic environments, which raises the question of what the underlying presynaptic mechanisms are and the relative importance of presynaptic and postsynaptic contributions to the faithful transfer of information. Changes in short-term depression under different acoustic conditions were a result of changes in presynaptic Ca²⁺ influx. Spike fidelity was affected by both presynaptic and postsynaptic changes after ear occlusion and was only affected by presynaptic changes after noise-rearing. These findings are important for understanding regulation of auditory synapses under normal conditions and also in disorders following noise exposure or conductive hearing loss.

在各种活动条件下，多种形式的体内稳态影响突触功能。突触前和突触后形式的稳态均很重要，但它们对保真度的相对影响尚不清楚。为了解决这个问题，我们研究了听觉神经突触到性别小鼠的耳蜗核中的丛状细胞上。这些突触随着声刺激的增加和减少而经历双向突触前和突触后稳态变化。我们发现年轻和成熟的突触在短期抑郁症中表现出类似的活动依赖性变化。使用螯合剂和成像的实验均表明，突触前Ca ^2+内流在噪声暴露后减少，而在结扎耳道后增加。相比之下，Ca ²⁺合作不受影响。使用特定拮抗剂的实验表明，阻塞会导致驱动神经递质释放的Ca ²⁺通道亚型发生变化。此外，动态钳制实验显示，穗的保真度主要取决于突触前抑制的变化，而突触后固有特性的变化也有一定作用。这些实验表明，突触前Ca ^2+内流在体内被稳态调节以增强突触保真度。

意义声明突触中的稳态机制在面对不同水平的活动时保持稳定的功能。幼年和成熟的听觉神经突触到丛生细胞上都会改变不同声学环境中的短期抑郁，这引发了一个问题，即潜在的突触前机制是什么，以及突触前和突触后贡献对忠实信息传递的相对重要性。不同声学条件下短期抑郁的变化是突触前Ca ²⁺变化的结果涌入。穗的保真度受耳朵闭塞后突触前和突触后变化的影响，并且仅受噪声产生后突触前变化的影响。这些发现对于理解正常条件下以及在噪声暴露或传导性听力损失后的疾病中听觉突触的调节非常重要。