Program in Neurosciences and Mental Health, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Nat Commun. 2019 Feb 18;10(1):826. doi: 10.1038/s41467-019-08452-2.
Synaptic heterogeneity is widely observed but its underpinnings remain elusive. We addressed this issue using mature calyx of Held synapses whose numbers of bouton-like swellings on stalks of the nerve terminals inversely correlate with release probability (Pr). We examined presynaptic Ca currents and transients, topology of fluorescently tagged knock-in Ca channels, and Ca channel-synaptic vesicle (SV) coupling distance using Ca chelator and inhibitor of septin cytomatrix in morphologically diverse synapses. We found that larger clusters of Ca channels with tighter coupling distance to SVs elevate Pr in stalks, while smaller clusters with looser coupling distance lower Pr in swellings. Septin is a molecular determinant of the differences in coupling distance. Supported by numerical simulations, we propose that varying the ensemble of two morphological modules containing distinct Ca channel-SV topographies diversifies Pr in the terminal, thereby establishing a morpho-functional continuum that expands the coding capacity within a single synapse population.
突触异质性广泛存在，但其潜在机制仍不清楚。我们使用成熟的 Held 神经突触的中心窝来解决这个问题，中心窝在神经末梢干上的囊泡样肿胀数量与释放概率（Pr）呈反比。我们使用 Ca 螯合剂和 septin 细胞基质抑制剂在形态多样的突触中检测了突触前 Ca 电流和瞬时变化、荧光标记的嵌合 Ca 通道的拓扑结构以及 Ca 通道-突触小泡（SV）的耦合距离。我们发现，与 SV 结合更紧密的 Ca 通道簇的数量增加会提高干上的 Pr，而与 SV 结合较松散的 Ca 通道簇的数量增加会降低肿胀处的 Pr。 septin 是影响耦合距离差异的分子决定因素。数值模拟支持了这样的假设，即包含不同 Ca 通道-SV 拓扑结构的两个形态模块的集合的变化使末端的 Pr 多样化，从而建立了一个形态-功能连续体，在单个突触群体中扩展了编码容量。
