Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, New York 14260.
Center for Hearing and Deafness, Department of Communicative Disorders and Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214.
J Neurosci. 2020 Sep 2;40(36):6896-6909. doi: 10.1523/JNEUROSCI.1175-19.2020. Epub 2020 Aug 3.
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 Ca influx decreased after noise exposure, and increased after ligating the ear canal. By contrast, Ca cooperativity was unaffected. Experiments using specific antagonists suggest that occlusion leads to changes in the Ca 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 Ca influx is homeostatically regulated to enhance synaptic fidelity. 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 Ca 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.
多种形式的内稳态在不同的活动条件下影响突触功能。 突触前和突触后的内稳态形式都很重要，但它们对保真度的相对影响尚不清楚。 为了解决这个问题，我们研究了雄性和雌性小鼠耳蜗核中听神经突触到毛细胞上的突触。 这些突触在增加和减少声刺激时会发生双向的突触前和突触后的内稳态变化。 我们发现，年轻和成熟的突触都表现出相似的活动依赖性短期抑郁变化。 使用螯合剂进行的实验和成像都表明，噪声暴露后，突触前 Ca 流入减少，而阻塞耳道后则增加。 相比之下，Ca 协同作用不受影响。 使用特定拮抗剂的实验表明，阻塞导致驱动神经递质释放的 Ca 通道亚型发生变化。 此外，动态箝位实验表明，尖峰保真度主要取决于突触前抑制的变化，而突触后内在特性的变化也有一定的贡献。 这些实验表明，突触前 Ca 流入是通过内稳态调节来增强突触保真度的。 突触中的内稳态机制可在不同的活动水平下维持稳定的功能。 幼年和成熟的听神经突触到毛细胞在不同的声环境中都会改变短期抑郁，这就提出了一个问题，即潜在的突触前机制是什么，以及突触前和突触后对信息的准确传递的相对重要性是什么。 在不同的声条件下，短期抑郁的变化是由于突触前 Ca 流入的变化所致。 尖峰保真度在耳阻塞后的前后变化都受到影响，而在噪声暴露后的内稳态变化仅受突触前变化的影响。 这些发现对于理解正常条件下听觉突触的调节以及噪声暴露或传导性听力损失后疾病的调节都很重要。
