Synapse-specific and plasticity-regulated AMPA receptor mobility tunes synaptic integration

Abstract

Synaptic responses adapt on millisecond-to-second timescales through short-term plasticity (STP), a key process that filters and transforms neuronal information. While STP is classically ascribed to presynaptic release mechanisms, postsynaptic receptor properties-particularly desensitization and surface diffusion-also shape synaptic responses. Here, we dissect pre- and postsynaptic contributions to synaptic adaptation using molecular tools to visualize glutamate release and manipulate AMPA receptor (AMPAR) diffusion in intact circuits. We find that synaptic gain during STP is tuned by synapse-specific regulation of AMPAR biophysics and diffusion-trapping. These features are determined constitutively by auxiliary subunit profiles and dynamically by activity-dependent signaling engaged during long-term plasticity. With modeling, we quantified how short-term synaptic dynamics are impacted by postsynaptic regulation of filtering properties, which broadened heterogeneity of filtering timescales to refine temporal selectivity in synaptic networks. By augmenting desensitization-mediated synaptic depression, AMPAR diffusion-trapping emerges as a fundamental regulatory mechanism of postsynaptic integration and circuit-level information processing.

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Cite

BibTeX RIS

BibTeX

@article{nowacka2026synapsespecific,
  title = {{Synapse-specific and plasticity-regulated AMPA receptor mobility tunes synaptic integration}},
  author = {Agata Nowacka and Angela Getz and Hanna Zieger and Maxime Malivert and Diogo Bessa-Neto and Elisabete Augusto and Christelle Breillat and Sophie Daburon and Cécile Lemoigne and Sébastien Marais and Mathieu Ducros and Alexandre Favereaux and Andrew Penn and Richard Naud and Matthieu Sainlos and Daniel Choquet},
  journal = {Neuron},
  year = {2026},
  month = oct,
  doi = {10.1016/j.neuron.2025.12.004},
  url = {https://hal.science/hal-05782482v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - JOUR
TI  - Synapse-specific and plasticity-regulated AMPA receptor mobility tunes synaptic integration
AU  - Agata Nowacka
AU  - Angela Getz
AU  - Hanna Zieger
AU  - Maxime Malivert
AU  - Diogo Bessa-Neto
AU  - Elisabete Augusto
AU  - Christelle Breillat
AU  - Sophie Daburon
AU  - Cécile Lemoigne
AU  - Sébastien Marais
AU  - Mathieu Ducros
AU  - Alexandre Favereaux
AU  - Andrew Penn
AU  - Richard Naud
AU  - Matthieu Sainlos
AU  - Daniel Choquet
PY  - 2026
DA  - 2026/10/06
JO  - Neuron
DO  - 10.1016/j.neuron.2025.12.004
UR  - https://hal.science/hal-05782482v1
AB  - Synaptic responses adapt on millisecond-to-second timescales through short-term plasticity (STP), a key process that filters and transforms neuronal information. While STP is classically ascribed to presynaptic release mechanisms, postsynaptic receptor properties-particularly desensitization and surface diffusion-also shape synaptic responses. Here, we dissect pre- and postsynaptic contributions to synaptic adaptation using molecular tools to visualize glutamate release and manipulate AMPA receptor (AMPAR) diffusion in intact circuits. We find that synaptic gain during STP is tuned by synapse-specific regulation of AMPAR biophysics and diffusion-trapping. These features are determined constitutively by auxiliary subunit profiles and dynamically by activity-dependent signaling engaged during long-term plasticity. With modeling, we quantified how short-term synaptic dynamics are impacted by postsynaptic regulation of filtering properties, which broadened heterogeneity of filtering timescales to refine temporal selectivity in synaptic networks. By augmenting desensitization-mediated synaptic depression, AMPAR diffusion-trapping emerges as a fundamental regulatory mechanism of postsynaptic integration and circuit-level information processing.
SN  - 0896-6273
ER  -

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