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. 2024 Oct 2;635(8038):398–405. doi: 10.1038/s41586-024-08027-2

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Extended Data Fig. 17 — The abundant CP-AMPARs in PV interneurons were removed by ① targeted expression of GluA2, which ② replaces them with CI-AMPARs. This causes several electrophysiological changes (ⓐ-ⓒ) and ③ increases orientation selectivity in the visual cortex or spatial selectivity in the hippocampus. In excitatory forebrain neurons, which primarily have CI-AMPARs, ④ knocking out GluA2 makes all AMPARs ⑤ calcium permeable. This leads to ⑥ lower orientation selectivity. These results collectively demonstrate a strong role of CP-AMPARs in deciding the feature selectivity of a neuron. Computational modeling reveals that of the three cardinal electrophysiological changes we detect with CP-AMPAR removal (green traces), ⓐ increased intrinsic excitability is likely to decrease selectivity (opposite to our findings), whereas ⓑ decreased inward rectification and ⓒ increased anti-Hebbian LTD are likely to increase feature selectivity (consistent with our findings), providing a potential mechanism of the increased orientation selectivity and spatial selectivity after CP-AMPAR removal observed.