Tao-Cheng Jung-Hwa
NINDS Electron Microscopy Facility National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA.
Mol Brain. 2025 Mar 31;18(1):28. doi: 10.1186/s13041-025-01198-7.
In mammalian brains, astroglia presence near glutamatergic excitatory synapses has generated the term "tripartite" junctions, based on the close association of astrocytic processes near the active zone formed by presynaptic axonal terminal and postsynaptic dendritic spines. One major function of these astrocytic processes is to take up glutamate that spill out of the synaptic cleft during activity, via glutamate transporters located on astroglial plasma membrane. Comapred to other regions of the brain, the cerebellar Purkinje spines in the molecular layer are virtually completely ensheathed by Bergman glia, a special type of astrocyte, unique to cerebellum. The present electron microscopy study classifies these peri-synaptic astrocytic processes (PAP) ensheathing the Purkinje spine synapses into three types based on structural criteria: (1) Type 1- astrocytic process is situated at the edge of the synaptic cleft immediately next to the synaptic active zone. Under fast perfusion fixation conditions where synapses were under resting states, ~ 58% of the PAP's were scored as Type 1. The occurrence frequency of Type 1 PAP significantly decreased to 25% upon a 5-8 min delay in perfusion fixation, where synapses were under stimulated states. (2) Type 2- astrocytic process covers part of the postsynaptic membrane containing the postsynaptic density (PSD), so that this part of the PSD is separated from its presynaptic terminal. Occurrence frequency of Type 2 PAP's significantly increased from ~ 14% under fast perfusion fixation to 31% upon delayed perfusion fixation, and the average length of the PSD edge covered by astroglia increased from 41 nm to 57 nm upon delayed perfusion fixation. (3) Type 3- astrocytic process is situated some distance away from the active zone, while the presynaptic axon terminal extends to enwrap the spine beyond the active zone. Occurrence frequency of Type 3 PAP's increased from 28 to 43% upon delayed perfusion fixation, and the average length between apposed axon terminal and spine beyond the synaptic cleft significantly increased from 98 to 209 nm upon delayed perfusion fixation. Thus, upon stimulation, the tripartite synaptic junctions undergo dynamic structural changes with the astrocytic processes moving into the open cleft to cover the exposed postsynaptic membrane containing PSD, the presynaptic axon terminals extending to wrap the postsynaptic spine beyond the synaptic cleft. Both structural changes may facilitate glutamate uptake to clear the transmitter spilled out from the synaptic cleft during intense activity and prevent damage from overstimulation.
在哺乳动物大脑中，由于星形胶质细胞的突起与由突触前轴突终末和突触后树突棘形成的活性区紧密相连，谷氨酸能兴奋性突触附近存在星形胶质细胞，这就产生了“三方”连接的概念。这些星形胶质细胞突起的一个主要功能是通过位于星形胶质细胞质膜上的谷氨酸转运体，摄取活动期间从突触间隙溢出的谷氨酸。与大脑的其他区域相比，分子层中的小脑浦肯野树突棘实际上完全被伯格曼胶质细胞包裹，伯格曼胶质细胞是小脑特有的一种特殊类型的星形胶质细胞。目前的电子显微镜研究根据结构标准将包裹浦肯野树突棘突触的这些突触周围星形胶质细胞突起（PAP）分为三种类型：（1）1型——星形胶质细胞突起位于突触间隙边缘，紧邻突触活性区。在突触处于静息状态的快速灌注固定条件下，约58%的PAP被归类为1型。在灌注固定延迟5 - 8分钟（此时突触处于刺激状态）时，1型PAP的出现频率显著降至25%。（2）2型——星形胶质细胞突起覆盖包含突触后致密部（PSD）的部分突触后膜，使得PSD的这部分与其突触前终末分离。2型PAP的出现频率从快速灌注固定时的约14%显著增加到延迟灌注固定时的31%，并且星形胶质细胞覆盖的PSD边缘平均长度从延迟灌注固定时的41纳米增加到57纳米。（3）3型——星形胶质细胞突起位于距活性区一定距离处，而突触前轴突终末延伸以包裹超出活性区的树突棘。3型PAP的出现频率在延迟灌注固定时从28%增加到43%，并且在延迟灌注固定时，突触间隙之外相对的轴突终末与树突棘之间的平均长度从98纳米显著增加到209纳米。因此，在刺激时，三方突触连接会发生动态结构变化，星形胶质细胞突起移入开放的突触间隙以覆盖包含PSD的暴露突触后膜，突触前轴突终末延伸以包裹超出突触间隙的突触后树突棘。这两种结构变化都可能促进谷氨酸的摄取，以清除在强烈活动期间从突触间隙溢出的神经递质，并防止过度刺激造成的损伤。
