Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice.

Autor: Tewari BP; Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA., Woo AM; Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA., Prim CE; Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA., Chaunsali L; Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA., Patel DC; Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA., Kimbrough IF; Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA., Engel K; School of Neuroscience, Virginia Tech, Blacksburg, VA, USA., Browning JL; School of Neuroscience, Virginia Tech, Blacksburg, VA, USA., Campbell SL; Department of Animal Sciences, Virginia Tech, Blacksburg, VA, USA., Sontheimer H; Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA. sontheimer@virginia.edu.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2024 Aug; Vol. 27 (8), pp. 1475-1488. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1038/s41593-024-01714-3
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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