Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Department of Biology, Texas A&M University, College Station, TX 77843.
Proc Natl Acad Sci U S A. 2021 Apr 27;118(17). doi: 10.1073/pnas.2018653118.
Long-term potentiation (LTP) is a cellular mechanism of learning and memory that results in a sustained increase in the probability of vesicular release of neurotransmitter. However, previous work in hippocampal area CA1 of the adult rat revealed that the total number of vesicles per synapse decreases following LTP, seemingly inconsistent with the elevated release probability. Here, electron-microscopic tomography (EMT) was used to assess whether changes in vesicle density or structure of vesicle tethering filaments at the active zone might explain the enhanced release probability following LTP. The spatial relationship of vesicles to the active zone varies with functional status. Tightly docked vesicles contact the presynaptic membrane, have partially formed SNARE complexes, and are primed for release of neurotransmitter upon the next action potential. Loosely docked vesicles are located within 8 nm of the presynaptic membrane where SNARE complexes begin to form. Nondocked vesicles comprise recycling and reserve pools. Vesicles are tethered to the active zone via filaments composed of molecules engaged in docking and release processes. The density of tightly docked vesicles was increased 2 h following LTP compared to control stimulation, whereas the densities of loosely docked or nondocked vesicles congregating within 45 nm above the active zones were unchanged. The tethering filaments on all vesicles were shorter and their attachment sites shifted closer to the active zone. These findings suggest that tethering filaments stabilize more vesicles in the primed state. Such changes would facilitate the long-lasting increase in release probability following LTP.
长期增强（LTP）是学习和记忆的细胞机制，导致神经递质囊泡释放的概率持续增加。然而，先前在成年大鼠海马 CA1 区的研究表明，LTP 后每个突触的囊泡总数减少，这似乎与释放概率的提高不一致。在这里，电子显微镜断层扫描（EMT）用于评估囊泡密度或囊泡连接丝结构的变化是否可以解释 LTP 后释放概率的提高。囊泡与活性区的空间关系随功能状态而变化。紧密停靠的囊泡接触突触前膜，具有部分形成的 SNARE 复合物，并在下次动作电位时准备释放神经递质。松散停靠的囊泡位于距突触前膜 8nm 的位置，SNARE 复合物开始形成。非停靠的囊泡构成回收和储备池。囊泡通过由参与对接和释放过程的分子组成的细丝与活性区连接。与对照刺激相比，LTP 后 2 小时，紧密停靠的囊泡密度增加，而聚集在活性区上方 45nm 范围内的松散停靠或非停靠囊泡的密度不变。所有囊泡上的连接丝更短，它们的附着点更靠近活性区。这些发现表明连接丝将更多的囊泡稳定在启动状态。这种变化将有助于 LTP 后释放概率的持久增加。
