We thank Vincent O’Connor, Erinn Gideons, and James Daniel for their helpful comments and critical reviews of the manuscript, and Klaus Nave for his support. We are grateful to Fritz Benseler, Klaus-Peter Hellmann, Bernd Hesse-Niessen, Ivonne Thanhäuser, Dayana Warnecke, Christiane Harenberg, Maik Schlieper, Lars van Werven, Dörte Hesse, Monika Raabe, Uwe Plessmann, and Aiko Miyakawa for excellent technical support, and to the Animal Facilities of the Max Planck Institute for Multidisciplinary Sciences for the maintenance of mouse colonies and support for mass spectrometry. We thank Johannes Hirrlinger, Frank Kirchhoff, Nicola Strenzke, and Gulnara Yamanbaeva for their advice. We thank Sandra Goebbels (Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany), Kevin R. Jones (University of Colorado, Boulder, CO, USA), and Hongkui Zeng (Allen Institute for Brain Science, Seattle, WA, USA) for providing Nex-Cre, EMX-Cre, and ROSA26-tdTom mouse lines, respectively; Thorsten Bus and Rolf Sprengel (Max Planck Institute for Medical Research, Heidelberg, Germany) for providing brain tissue and tissue extracts of control and Gria1−/− mice; and Jorge E. Azevedo (Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal), David Baltimore (California Institute of Technology, Pasadena, CA, USA), Richard Huganir (Johns Hopkins University School of Medicine, Baltimore, MD, USA), Didier Trono (Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland), Robin Shaw (The Nora Eccles Harrison CVRTI, The University of Utah, Salt Lake City, UT, USA), and Marc Timmers (German Cancer Consortium (DKTK), Freiburg, Germany) for providing plasmids.

This work was supported by Canadian Institutes of Health Research Foundation (D. Rotin), the German Research Foundation (SPP1365/KA3423/1-1 and KA3423/3-1, H. Kawabe; SPP1757/SA2114/2-1 and SA2114/2-2, G. Saher), the Fritz Thyssen Foundation (H. Kawabe), and the Japan Society for the Promotion of Science (JSPS) KAKENHI grant number JP20K06536 (K. Hanamura), JP22K07864 (N. Koganezawa), JP22H05526 (N. Koganezawa), JP15K21769 (H. Kawabe), JP20K07334 (H. Kawabe), JSPS Core-to-Core program (grant number JPJSCCA20220007) (H. Kawabe), and The Mother and Child Health Foundation (grant number 29-9, H. Kawabe; grant number R03-K1-2, N. Koganezawa), Ohsumi Frontier Science Foundation (H. Kawabe), the Takeda Science Foundation (N. Koganezawa and H. Kawabe), Daiichi Sankyo Foundation of Life Science (H. Kawabe), TERUMO Life Science Foundation (H. Kawabe), The Naito Foundation (H. Kawabe), and The Uehara Memorial Foundation (H. Kawabe). Open Access funding provided by the Max Planck Society.

Author contributions: B. Altas: conceptualization, project administration, investigation, validation, formal analysis, writing-original draft, and writing-review and editing; H.-J. Rhee, A. Ju, H.C. Solís, S. Karaca, J. Winchenbach, O. Kaplan Arabaci, M. Schwark, M.C. Ambrozkiewicz, C. Lee, L. Spieth, G.L. Wieser, V.K. Chaugule, I. Majoul, M.A. Hassan, R. Goel, and S.M. Wojcik: investigation, validation, formal analysis, and writing-review and editing; A. Pichler, M. Mitkovski, L. de Hoz, A. Poulopoulos, H. Urlaub, O. Jahn, G. Saher, N. Brose, and J. Rhee: conceptualization and writing-review and editing; N. Koganezawa and K. Hanamura: investigation, validation, formal analysis, writing-review and editing, and provided funding for the research; D. Rotin: conceptualization, writing-review and editing, and provided funding for the research; H. Kawabe: supervision, conceptualization, provided funding for the research, project administration, writing-review and editing.