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In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment
In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment
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In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment
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In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment
In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment

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In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment
In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment
Paper

In vivo modulation of network activity drives the nanoscale reorganisation of axo-axonic synapses at the axon initial segment

2025,2024
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Overview
Chemical synapses control their strength through the nanoscale clustering of postsynaptic receptors into sub-synaptic domains (SSDs). Despite their importance in synapse function, the properties and plasticity of these domains are not well understood in vivo, particularly in inhibitory synapses. We used direct Stochastic Optical Resolution Microscopy (dSTORM) to show that Gephyrin, the main inhibitory receptor scaffold protein, is organised into SSDs in vivo, with distinct arrangements depending on their sub-cellular location and presynaptic partner. Furthermore, chronic chemogenetic increases in cortical activity caused a reduction in Gephyrin SSD volume specifically in axo-axonic, but not axo-dendritic, synapses. Functionally, this resulted in a weakening of axo-axonic contacts. We show that the nanoscale arrangement of synapses in the brain is plastic and used to fine-tune synaptic gain in vivo.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Manuscript text and figures have been revised.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory