Calorie-restricted (CR) diet has multiple beneficial effects on brain function. Here we report morphological and functional changes in hippocampal astrocytes in 3-months-old mice subjected to 1 month of the diet. Whole-cell patch-clamp recordings were performed in the CA1 stratum (str.) radiatum astrocytes of hippocampal slices. The cells were also loaded with fluorescent dye through the patch pipette. CR did not affect the number of astrocytic branches but increased the volume fraction (VF) of distal perisynaptic astrocytic leaflets. The astrocyte growth did not lead to a decrease in the cell input resistance, which may be attributed to a decrease in astrocyte coupling through the gap junctions. Western blotting revealed a decrease in the expression of Cx43 but not Cx30. Immunocytochemical analysis demonstrated a decrease in the density and size of Cx43 clusters. Cx30 cluster density did not change, while their size increased in the vicinity of astrocytic soma. CR shortened K⁺ and glutamate transporter currents in astrocytes in response to 5 × 50 Hz Schaffer collateral stimulation. However, no change in the expression of astrocytic glutamate transporter 1 (GLT-1) was observed, while the level of glutamine synthetase (GS) decreased. These findings suggest that enhanced enwrapping of synapses by the astrocytic leaflets reduces glutamate and K⁺ spillover. Reduced spillover led to a decreased contribution of extrasynaptic N2B containing N-methyl-D-aspartate receptors (NMDARs) to the tail of burst-induced EPSCs. The magnitude of long-term potentiation (LTP) in the glutamatergic CA3–CA1 synapses was significantly enhanced after CR. This enhancement was abolished by N2B-NMDARs antagonist. Our findings suggest that astrocytic morphofunctional remodeling is responsible for enhanced synaptic plasticity, which provides a basis for improved learning and memory reported after CR.

限制热量（CR）饮食对脑功能有多种有益作用。在这里，我们报告了3个月大的小鼠饮食1个月后海马星形胶质细胞的形态和功能变化。全细胞膜片钳记录在CA1层（str。）放射线中进行海马切片的星形胶质细胞。通过贴片移液管还向细胞加载了荧光染料。CR不会影响星形细胞分支的数量，但会增加突触周围星形细胞远端小叶的体积分数（VF）。星形胶质细胞的生长并未导致细胞输入阻力的降低，这可能归因于通过间隙连接的星形胶质细胞偶联的降低。蛋白质印迹显示Cx43表达降低，但Cx30表达未降低。免疫细胞化学分析表明，Cx43簇的密度和大小均降低。Cx30簇密度没有变化，而在星形细胞体附近增大了。CR缩短了K ⁺星形胶质细胞中的谷氨酸和谷氨酸转运蛋白电流响应5×50 Hz Schaffer附带刺激。但是，没有观察到星形细胞谷氨酸转运蛋白1（GLT-1）的表达变化，而谷氨酰胺合成酶（GS）的水平下降。这些结果表明，由星形胶质细胞突触传单增强enwrapping降低谷氨酸和K ⁺溢出。溢出的减少导致突触诱导的EPSC尾部含有N-甲基-D-天冬氨酸受体（NMDARs）的突触外N2B减少。CR后，谷氨酸能CA3–CA1突触的长期增强（LTP）幅度显着提高。N2B-NMDARs拮抗剂取消了这种增强作用。我们的发现表明，星形细胞形态功能重塑是突触可塑性增强的原因，这为CR后报道的学习和记忆改善提供了基础。