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Short-Range Functional Interaction Between Connexin35 and Neighboring Chemical Synapses

机译:连接蛋白35与邻近的化学突触之间的短程功能相互作用。

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Auditory afferents terminating as mixed, electrical, and chemical, synapses on the goldfish Mauthner cells constitute an ideal experimental model to study the properties of gap junctions in the nervous system as well as to explore possible functional interactions with the other major form of interneuronal communication—chemically mediated synapses. By combining confocal microscopy and freeze-fracture replica immunogold labeling (FRIL), we found that gap junctions at these synapses contain connexin35 (Cx35), the fish ortholog of the neuron-specific human and mouse connexin36 (Cx36). Conductance of gap junction channels at these endings is known to be dynamically modulated by the activity of their co-localized chemically mediated glutamatergic synapses. By using simultaneous pre- and postsynaptic recordings at these single terminals, we demonstrate that such functional interaction takes place in the same ending, within a few micrometers. Accordingly, we also found evidence by confocal and FRIL double-immunogold labeling that the NR1 subunit of the NMDA glutamate receptor, proposed to be a key regulatory element, is present at postsynaptic densities closely associated with gap junction plaques containing Cx35. Given the widespread distribution of Cx35- and Cx36-mediated electrical synapses and glutamatergic synapses, our data suggest that the local functional interactions observed at these identifiable junctions may also apply to other electrical synapses, including those in mammalian brain.
机译:听觉传入以金鱼Mauthner细胞上的混合突触,电突触和化学突触终止,构成了理想的实验模型,用于研究神经系统间隙连接的特性以及探索与其他主要形式的神经元间交流的功能相互作用-化学介导的突触。通过共聚焦显微镜和冷冻断裂复制免疫金标记(FRIL)的结合,我们发现这些突触的间隙连接处包含连接蛋白35(Cx35),这是神经元特异性人类和小鼠连接蛋白36(Cx36)的鱼类直系同源物。已知在这些末端的间隙连接通道的电导是通过其共定位的化学介导的谷氨酸能突触的活性动态调节的。通过在这些单个末端同时使用突触前和突触后录音,我们证明了这种功能性相互作用发生在同一末端(几微米内)。因此,我们还发现通过共聚焦和FRIL双免疫金标记的证据表明,NMDA谷氨酸受体的NR1亚基被认为是关键的调控元件,存在于与Cx35间隙连接斑块紧密相关的突触后密度。鉴于Cx35和Cx36介导的电突触和谷氨酸能突触的广泛分布,我们的数据表明,在这些可识别的连接处观察到的局部功能性相互作用也可能适用于其他电突触,包括在哺乳动物脑中。

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