Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show that synaptic terminals of fast-spiking interneurons localize to holes in the PNNs in the adult mouse somatosensory cortex. Approximately 95% of holes in the PNNs contain synapses and astrocytic processes expressing Kir4.1, glutamate and GABA transporters. Hence, holes in the PNNs contain tripartite synapses. In the adult mouse brain, PNN degradation causes an expanded astrocytic coverage of the neuronal somata without altering the axon terminals. The loss of PNNs impairs astrocytic transmitter and potassium uptake, resulting in the spillage of glutamate into the extrasynaptic space. Our data show that PNNs and astrocytes cooperate to contain synaptically released signals in physiological conditions. Their combined action is altered in mouse models of Alzheimer’s disease and epilepsy where PNNs are disrupted.

神经元周围网 (PNN) 是密集的细胞外基质，覆盖快速放电抑制性神经元的细胞体。 PNN 稳定突触，抑制突触可塑性。在这里，我们展示了快速尖峰中间神经元的突触末端定位于成年小鼠体感皮层 PNN 中的孔。 PNN 中大约 95% 的孔包含表达 Kir4.1、谷氨酸和 GABA 转运蛋白的突触和星形胶质细胞过程。因此，PNN 中的孔包含三方突触。在成年小鼠大脑中，PNN 降解会导致神经元胞体的星形胶质细胞覆盖范围扩大，但不会改变轴突末端。 PNN 的缺失会损害星形细胞递质和钾的吸收，导致谷氨酸溢出到突触外空间。我们的数据表明，PNN 和星形胶质细胞在生理条件下合作抑制突触释放的信号。在 PNN 被破坏的阿尔茨海默病和癫痫小鼠模型中，它们的联合作用发生了改变。