Tewari Bhanu P, Woo AnnaLin M, Prim Courtney E, Chaunsali Lata, Kimbrough Ian F, Engel Kaliroi, Browning Jack L, Campbell Susan L, Sontheimer Harald
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA.
School of Neuroscience, Virginia Tech, Blacksburg, VA, USA.
Res Sq. 2023 Feb 2:rs.3.rs-2501039. doi: 10.21203/rs.3.rs-2501039/v1.
Perineuronal nets (PNNs) are dense, negatively charged extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. Synapses can be embedded and stabilized by PNNs believed to prevent synaptic plasticity. We find that in cortical fast-spiking interneurons synaptic terminals localize to perforations in the PNNs, 95% of which contain either excitatory or inhibitory synapses or both. The majority of terminals also colocalize with astrocytic processes expressing Kir4.1 as well as glutamate (Glu) and GABA transporters, hence can be considered tripartite synapses. In the adult brain, degradation of PNNs does not alter axonal terminals but causes expansion of astrocytic coverage of the neuronal somata. However, loss of PNNs impairs astrocytic transmitter and K+ uptake and causes spillage of synaptic Glu into the extrasynaptic space. This data suggests a hitherto unrecognized role of PNNs, to synergize with astrocytes to contain synaptically released signals.
神经周网（PNNs）是覆盖快速放电抑制性神经元细胞体的致密、带负电荷的细胞外基质。突触可被认为能防止突触可塑性的神经周网嵌入并稳定。我们发现，在皮质快速放电中间神经元中，突触终末定位于神经周网的穿孔处，其中95%含有兴奋性或抑制性突触或两者皆有。大多数终末还与表达Kir4.1以及谷氨酸（Glu）和GABA转运体的星形胶质细胞突起共定位，因此可被视为三方突触。在成人大脑中，神经周网的降解不会改变轴突终末，但会导致星形胶质细胞对神经元胞体覆盖范围的扩大。然而，神经周网的缺失会损害星形胶质细胞对递质和K+的摄取，并导致突触Glu泄漏到突触外空间。这些数据表明神经周网有一个迄今未被认识到的作用，即与星形胶质细胞协同作用以限制突触释放的信号。
