Nam Andrea J, Kuwajima Masaaki, Parker Patrick H, Bowden Jared B, Abraham Wickliffe C, Harris Kristen M
bioRxiv. 2025 May 14:2025.05.13.653827. doi: 10.1101/2025.05.13.653827.
Perisynaptic astroglia provide critical molecular and structural support to regulate synaptic transmission and plasticity in the nanodomain of the axon-spine interface. Three-dimensional reconstruction from serial section electron microscopy (3DEM) was used to investigate relationships between perisynaptic astroglia and dendritic spine synapses undergoing plasticity in the hippocampus of awake adult male rats. Delta-burst stimulation (DBS) of the medial perforant pathway induced long-term potentiation (LTP) in the middle molecular layer and concurrent long-term depression (cLTD) in the outer molecular layer of the dentate gyrus. The contralateral hippocampus received baseline stimulation as a within-animal control. Brains were obtained 30 minutes or 2 hours after DBS onset. An automated 3DEM pipeline was developed to enable unbiased quantification of astroglial coverage at the perimeter of the axon-spine interface. Under all conditions, >85% of synapses had perisynaptic astroglia processes within 120 nm of some portion of the perimeter. LTP broadened the distribution of spine sizes while reducing the presence and proximity of perisynaptic astroglia near the axon-spine interface of large spines. In contrast, cLTD transiently reduced the length of the axon-spine interface perimeter without substantially altering astroglial apposition. The postsynaptic density was discovered to be displaced from the center of the axon-spine interface, with this offset increasing during LTP and decreasing during cLTD. Astroglial access to the postsynaptic density was diminished during LTP and enhanced during cLTD, in parallel with changes in spine size. Thus, access of perisynaptic astroglia to synapses is dynamically modulated during LTP and cLTD alongside synaptic remodeling.
Perisynaptic astroglia provide critical molecular and structural regulation of synaptic plasticity underlying learning and memory. The hippocampal dentate gyrus, a brain region crucial for learning and memory, was found to have perisynaptic astroglia at the axon-spine interface of >85% of excitatory synapses measured. Long-term potentiation triggered the retraction of perisynaptic astroglia processes selectively from large synapses. This retraction decreased access of perisynaptic astroglia to the postsynaptic density, which was discovered to be located off-center in the axon-spine interface. Concurrent long-term depression temporarily (< 2 h) decreased spine perimeter and thus increased access of synapses to perisynaptic astroglia. These findings provide new insights into how the structural dynamics of spines and synapses shape access to perisynaptic astroglia.
突触周围星形胶质细胞提供关键的分子和结构支持，以调节轴突 - 树突棘界面纳米域中的突触传递和可塑性。使用连续切片电子显微镜进行的三维重建（3DEM）来研究清醒成年雄性大鼠海马中突触周围星形胶质细胞与经历可塑性的树突棘突触之间的关系。内侧穿通通路的δ波爆发刺激（DBS）在齿状回的中层分子层诱导长时程增强（LTP），并在外层分子层同时诱导长时程抑制（cLTD）。对侧海马接受基线刺激作为动物内对照。在DBS开始后30分钟或2小时获取大脑。开发了一种自动化的3DEM流程，以实现对轴突 - 树突棘界面周边星形胶质细胞覆盖的无偏量化。在所有条件下，超过85%的突触在周边的某些部分120纳米范围内有突触周围星形胶质细胞过程。LTP拓宽了棘突大小的分布，同时减少了大棘突的轴突 - 树突棘界面附近突触周围星形胶质细胞的存在和接近程度。相比之下，cLTD暂时缩短了轴突 - 树突棘界面周边的长度，而没有实质性改变星形胶质细胞的附着。发现突触后致密物从轴突 - 树突棘界面的中心移位，这种偏移在LTP期间增加，在cLTD期间减少。与棘突大小的变化并行，在LTP期间突触周围星形胶质细胞对突触后致密物的接触减少，在cLTD期间增加。因此，在LTP和cLTD期间，伴随着突触重塑，突触周围星形胶质细胞对突触的接触受到动态调节。
突触周围星形胶质细胞为学习和记忆背后的突触可塑性提供关键的分子和结构调节。海马齿状回是对学习和记忆至关重要的脑区，发现在所测量的超过85%的兴奋性突触的轴突 - 树突棘界面处有突触周围星形胶质细胞。长时程增强选择性地触发突触周围星形胶质细胞过程从大突触处回缩。这种回缩减少了突触周围星形胶质细胞对突触后致密物的接触，发现突触后致密物位于轴突 - 树突棘界面的偏离中心位置。同时发生的长时程抑制暂时（<2小时）减小了棘突周长，从而增加了突触对突触周围星形胶质细胞的接触。这些发现为棘突和突触的结构动力学如何塑造对突触周围星形胶质细胞的接触提供了新的见解。
