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首页> 外文期刊>Neuron >Basal GABA regulates GABA(B)R conformation and release probability at single hippocampal synapses.
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Basal GABA regulates GABA(B)R conformation and release probability at single hippocampal synapses.

机译：基底GABA调节单个海马突触的GABA（B）R构象和释放概率。

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摘要

Presynaptic GABA(B) receptor (GABA(B)R) heterodimers are composed of GB(1a)/GB(2) subunits and critically influence synaptic and cognitive functions. Here, we explored local GABA(B)R activation by integrating optical tools for monitoring receptor conformation and synaptic vesicle release at individual presynaptic boutons of hippocampal neurons. Utilizing fluorescence resonance energy transfer (FRET) spectroscopy, we detected a wide range of FRET values for CFP/YFP-tagged GB(1a)/GB(2) receptors that negatively correlated with release probabilities at single synapses. High FRET of GABA(B)Rs associated with low release probability. Notably, pharmacological manipulations that either reduced or increased basal receptor activation decreased intersynapse variability of GB(1a)/GB(2) receptor conformation. Despite variability along axons, presynaptic GABA(B)R tone was dendrite specific, having a greater impact on synapses at highly innervated proximal branches. Prolonged neuronal inactivity reduced basal receptor activation, leading to homeostatic augmentation of release probability. Our findings suggest that local variations in basal GABA concentration are a major determinant of GB(1a)/GB(2) conformational variability, which contributes to heterogeneity of neurotransmitter release at hippocampal synapses.
机译：突触前GABA（B）受体（GABA（B）R）异二聚体由GB（1a）/ GB（2）亚基组成，并严重影响突触和认知功能。在这里，我们通过集成光学工具来探索局部GABA（B）R激活，以监测海马神经元突触前突突中的受体构象和突触囊泡释放。利用荧光共振能量转移（FRET）光谱，我们检测到CFP / YFP标签的GB（1a）/ GB（2）受体的FRET值范围很广，这些值与单个突触的释放概率负相关。 GABA（B）Rs的高FRET与低释放概率相关。值得注意的是，降低或增加基础受体激活的药理学操作降低了GB（1a）/ GB（2）受体构象的突触间变异性。尽管沿轴突变化，突触前GABA（B）R音是树突特异性的，对高度支配的近端分支的突触影响更大。长时间的神经元不活动会减少基础受体的激活，导致稳态增加释放的可能性。我们的发现表明，基础GABA浓度的局部变化是GB（1a）/ GB（2）构象变异的主要决定因素，这有助于海马突触释放神经递质的异质性。

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