Proper brain function requires a balance between excitatory and inhibitory neuronal activity. This balance, which is disrupted in various neural disorders, ultimately depends on the functional properties of both excitatory and inhibitory neurons; however, how the physiological properties of presynaptic terminals are controlled in these neurons is largely unknown. In this study, we generated pHluorin-conjugated, synaptic vesicle-specific tracers that are preferentially expressed in excitatory or inhibitory nerve terminals. We found that synaptic vesicle recycling is ∼1.8-fold slower in inhibitory nerve terminals than excitatory nerve terminals, resulting in reduced efficacy of synaptic transmission in inhibitory presynaptic terminals during repetitive activities. Interestingly, this relative difference in trafficking efficiency is mediated by synaptic vesicle protein 2A (SV2A), which is more highly expressed in inhibitory synapses and differentially controls sorting of synaptic protein, synaptotagmin I. These findings indicate that SV2A coordinates distinct properties of synaptic vesicle recycling between excitatory and inhibitory synapses.

正常的大脑功能需要在兴奋性和抑制性神经元活动之间取得平衡。这种平衡在各种神经疾病中被破坏，最终取决于兴奋性和抑制性神经元的功能特性。然而，在这些神经元中如何控制突触前末梢的生理特性在很大程度上是未知的。在这项研究中，我们生成了 pHluorin 共轭的突触囊泡特异性示踪剂，这些示踪剂优先在兴奋性或抑制性神经末梢中表达。我们发现抑制性神经末梢的突触小泡循环比兴奋性神经末梢慢 1.8 倍，导致重复活动期间抑制性突触前末梢突触传递的效率降低。有趣的是，