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Publication : Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice.

First Author  Tewari BP Year  2024
Journal  Nat Neurosci Volume  27
Issue  8 Pages  1475-1488
PubMed ID  39020018 Mgi Jnum  J:353072
Mgi Id  MGI:7707514 Doi  10.1038/s41593-024-01714-3
Citation  Tewari BP, et al. (2024) Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice. Nat Neurosci 27(8):1475-1488
abstractText  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.
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