大多数神经系统结合了递质介导的和直接的细胞-细胞通讯,被称为“化学”和“电”突触,分别。化学突触可以通过它们的多个结构组分来识别。电突触是,另一方面,通常由两个神经元过程之间的间隙连接(一组细胞间通道)的存在定义。然而,而间隙连接提供了通信机制,电传输是否需要额外的细胞结构的贡献是未知的。我们在斑马鱼Mauthner细胞上可识别的单个突触接触中研究了这个问题,间隙连接与神经递质释放的专业化共存,并且接触明确定义了突触的解剖极限。这些单个接触的扩展显微镜显示了与各种突触结构有关的蛋白质的发生率和空间分布的详细图。通过其分子组分的存在来鉴定可变大小的多个间隙连接。值得注意的是,突触接触的大部分表面被交错的间隙连接和粘附连接的组件占据,表明这两种结构之间有密切的功能联系。相比之下,谷氨酸受体被限制在接触的小周边部分,这表明大部分突触区域作为电突触。因此,我们的结果揭示了一个电突触的总体组织,但是有多个缝隙连接,与已知为粘附连接成分的结构和信号分子密切相关。这些细胞间结构之间的关系将有助于建立在整个动物连接体中发现的电突触的边界,并提供对电突触的结构组织和功能多样性的了解。
Most nervous systems combine both transmitter-mediated and direct cell-cell communication, known as \'chemical\' and \'electrical\' synapses, respectively. Chemical synapses can be identified by their multiple structural components. Electrical synapses are, on the other hand, generally defined by the presence of a \'gap junction\' (a cluster of intercellular channels) between two neuronal processes. However, while gap junctions provide the communicating mechanism, it is unknown whether electrical transmission requires the contribution of additional cellular structures. We investigated this question at identifiable single synaptic contacts on the zebrafish Mauthner cells, at which gap junctions coexist with specializations for neurotransmitter release and where the contact unequivocally defines the anatomical limits of a synapse. Expansion microscopy of these single contacts revealed a detailed map of the incidence and spatial distribution of proteins pertaining to various synaptic structures. Multiple gap junctions of variable size were identified by the presence of their molecular components. Remarkably, most of the synaptic contact\'s surface was occupied by interleaving gap junctions and components of adherens junctions, suggesting a close functional association between these two structures. In contrast, glutamate receptors were confined to small peripheral portions of the contact, indicating that most of the synaptic area functions as an electrical synapse. Thus, our results revealed the overarching organization of an electrical synapse that operates with not one, but multiple gap junctions, in close association with structural and signaling molecules known to be components of adherens junctions. The relationship between these intercellular structures will aid in establishing the boundaries of electrical synapses found throughout animal connectomes and provide insight into the structural organization and functional diversity of electrical synapses.
Neurons communicate with each other through specialized structures known as synapses. At chemical synapses, the cells do not physically interact as they rely instead on molecules called neurotransmitters to pass along signals. At electrical synapses, however, neurons are directly connected via gap junctions, which are clusters of intercellular channels that allow ions and other small compounds to move from one cell to another. Both electrical and chemical synapses play critical roles in neural circuits, and both exhibit some amount of plasticity – they weaken or strengthen depending on how often they are used, an important feature for the brain to adapt to the needs of the environment. Yet the structure and molecular organization of electrical synapses have remained poorly understood compared to their chemical counterparts. In response, Cárdenas-García, Ijaz and Pereda took advantage of a new approach known as expansion microscopy to examine the electrical synapse that connects neurons bringing sound information to a pair of unusually large neurons in the brain of most bony fish. With this method, a biological sample is prepared in such a way that its size increases, but the relative position of its components is preserved. This allows scientists to better observe structures that would otherwise be too difficult to capture using traditional microscopy techniques. Experiments in larval zebrafish revealed that contrary to previous assumptions, the electrical synapse was formed of not one but multiple gap junctions of various sizes closely associated with a range of structural and signaling molecules typically found in adherens junctions (a type of structure that physically links cells together). The team suggests that these molecular actors could work to ensure that the multiple gap junctions act in concert at the synapse. Overall, these findings offer a new perspective on how electrical synapses are organized and regulated, which refines our understanding of how the nervous system functions both in health and in disease.