{"OA_place":"publisher","language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","creator":"dernst","file_size":5326608,"access_level":"open_access","file_id":"21392","date_updated":"2026-03-02T15:21:27Z","success":1,"date_created":"2026-03-02T15:21:27Z","file_name":"2026_NatureMetab_AmrapaliVishwanath.pdf","checksum":"365932a599d05bc9ce8a57204e7a1465","relation":"main_file"}],"author":[{"last_name":"Amrapali Vishwanath","full_name":"Amrapali Vishwanath, Anjali","first_name":"Anjali"},{"last_name":"Comyn","full_name":"Comyn, Typhaine","first_name":"Typhaine"},{"full_name":"Mira, Rodrigo G.","first_name":"Rodrigo G.","last_name":"Mira"},{"last_name":"Brossier","first_name":"Claire","full_name":"Brossier, Claire"},{"full_name":"Pascual-Caro, Carlos","first_name":"Carlos","last_name":"Pascual-Caro"},{"last_name":"Faour","full_name":"Faour, Maya","first_name":"Maya"},{"last_name":"Boumendil","first_name":"Kahina","full_name":"Boumendil, Kahina"},{"full_name":"Chintaluri, Chaitanya","orcid":"0000-0003-4252-1608","first_name":"Chaitanya","last_name":"Chintaluri","id":"BA06AFEE-A4BA-11EA-AE5C-14673DDC885E"},{"last_name":"Ramon-Duaso","full_name":"Ramon-Duaso, Carla","first_name":"Carla"},{"last_name":"Fan","first_name":"Ruolin","full_name":"Fan, Ruolin"},{"last_name":"Ghosh","first_name":"Kishalay","full_name":"Ghosh, Kishalay"},{"first_name":"Helen","full_name":"Farrants, Helen","last_name":"Farrants"},{"first_name":"Jean-Paul","full_name":"Berwick, Jean-Paul","last_name":"Berwick"},{"full_name":"Sivakumar, Riya","first_name":"Riya","last_name":"Sivakumar"},{"full_name":"Lopez-Manzaneda, Mario","first_name":"Mario","last_name":"Lopez-Manzaneda"},{"last_name":"Schreiter","full_name":"Schreiter, Eric R.","first_name":"Eric R."},{"last_name":"Preat","first_name":"Thomas","full_name":"Preat, Thomas"},{"orcid":"0000-0003-3295-6181","full_name":"Vogels, Tim P","first_name":"Tim P","last_name":"Vogels","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425"},{"full_name":"Rangaraju, Vidhya","first_name":"Vidhya","last_name":"Rangaraju"},{"last_name":"Busquets-Garcia","first_name":"Arnau","full_name":"Busquets-Garcia, Arnau"},{"first_name":"Pierre-Yves","full_name":"Plaçais, Pierre-Yves","last_name":"Plaçais"},{"last_name":"Pavlowsky","first_name":"Alice","full_name":"Pavlowsky, Alice"},{"last_name":"de Juan-Sanz","full_name":"de Juan-Sanz, Jaime","first_name":"Jaime"}],"type":"journal_article","publication_status":"published","year":"2026","intvolume":"         8","publisher":"Springer Nature","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1038/s42255-026-01451-w","oa_version":"Published Version","date_published":"2026-02-11T00:00:00Z","day":"11","issue":"2","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"article_processing_charge":"Yes (in subscription journal)","title":"Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species","pmid":1,"publication_identifier":{"eissn":["2522-5812"]},"PlanS_conform":"1","publication":"Nature Metabolism","_id":"21378","department":[{"_id":"TiVo"}],"date_created":"2026-03-02T10:04:49Z","ddc":["570"],"volume":8,"oa":1,"OA_type":"hybrid","acknowledgement":"We thank all members of the laboratory of J.d.J.-S. for insightful discussions and comments. We thank S. Perez for technical assistance. This work was made possible by the Paris Brain Institute Diane Barriere Chair in Synaptic Bioenergetics awarded to J.d.J.-S., who is also supported by an ERC Starting Grant (SynaptoEnergy, European Research Council; ERC-StG-852873), 2019 ATIP-Avenir Grant (CNRS, Inserm), a Big Brain Theory Grant (ICM Foundation) and a Kavli Exploratory Award (Kavli Foundation). This work was also supported by an ERC Advanced Grant (EnergyMeMo; ERC-AdG-741550) to T.P. and grants from the Agence Nationale de la Recherche to P.Y.P. (ANR-20-CE92-0047-01), T.P. (ANR-23-CE16-0029-01), A.P. and J.d.J.-S. (ANR-22-CE16-0020) and J.d.J.-S. (ANR-24-CE16-0221). T.P., P.Y.P. and J.d.J.-S. are permanent CNRS researchers. A.P. is a permanent ESPCI associate professor. T.C. was funded by the French Ministry of Research and the Fondation pour la Recherche Médicale. V.R. was funded by the Max Planck Society, the Chan Zuckerberg Initiative DAF, an advised fund of the Silicon Valley Community Foundation grant number 2024-349543 and the NIH Director’s New Innovator Award (DP2 MH140148). A.B.-G. and C.R.-D. received funding from an ERC Starting Grant (HighMemory; ERC-StG-948217), the Ministry of Economy and Competitiveness (PID2021-122795OB-I00) and the Departament d’Economia i Coneixement de la Generalitat de Catalunya (SGR 00022). T.P.V. was funded by the Wellcome Trust and a Royal Society Sir Henry Dale Research Fellowship (WT100000) and a Wellcome Trust Senior Research Fellowship (214316/Z/18/Z). K.G. was supported by the DIM C-BRAINS, funded by the Conseil Régional d’Ile-de-France. The contributions of H.F. and E.R.S. were supported by the Howard Hughes Medical Institute. The PHENO-ICMice animal Core at ICM is supported by two ‘Investissements d’avenir’ (ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS) and the Fondation pour la Recherche Médicale.","external_id":{"pmid":["41673453"]},"article_type":"original","month":"02","has_accepted_license":"1","project":[{"_id":"c084a126-5a5b-11eb-8a69-d75314a70a87","name":"What’s in a memory? Spatiotemporal dynamics in strongly coupled recurrent neuronal networks.","grant_number":"214316/Z/18/Z"}],"abstract":[{"text":"From insects to mammals, essential brain functions, such as forming long-term memories (LTMs), increase metabolic activity in stimulated neurons to meet the energetic demand associated with brain activation. However, while impairing neuronal metabolism limits brain performance, whether expanding the metabolic capacity of neurons boosts brain function remains poorly understood. Here, we show that LTM formation of flies and mice can be enhanced by increasing mitochondrial metabolism in central memory circuits. By knocking down the mitochondrial Ca2+ exporter Letm1, we favour Ca2+ retention in the mitochondrial matrix of neurons due to reduction of mitochondrial H+/Ca2+ exchange. The resulting increase in mitochondrial Ca2+ over-activates mitochondrial metabolism in neurons of central memory circuits, leading to improved LTM storage in training paradigms in which wild-type counterparts of both species fail to remember. Our findings unveil an evolutionarily conserved mechanism that controls mitochondrial metabolism in neurons and indicate its involvement in shaping higher brain functions, such as LTM.","lang":"eng"}],"status":"public","quality_controlled":"1","date_updated":"2026-03-02T15:23:10Z","citation":{"ista":"Amrapali Vishwanath A, Comyn T, Mira RG, Brossier C, Pascual-Caro C, Faour M, Boumendil K, Chintaluri C, Ramon-Duaso C, Fan R, Ghosh K, Farrants H, Berwick J-P, Sivakumar R, Lopez-Manzaneda M, Schreiter ER, Preat T, Vogels TP, Rangaraju V, Busquets-Garcia A, Plaçais P-Y, Pavlowsky A, de Juan-Sanz J. 2026. Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species. Nature Metabolism. 8(2), 467–488.","chicago":"Amrapali Vishwanath, Anjali, Typhaine Comyn, Rodrigo G. Mira, Claire Brossier, Carlos Pascual-Caro, Maya Faour, Kahina Boumendil, et al. “Mitochondrial Ca2+ Efflux Controls Neuronal Metabolism and Long-Term Memory across Species.” <i>Nature Metabolism</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s42255-026-01451-w\">https://doi.org/10.1038/s42255-026-01451-w</a>.","short":"A. Amrapali Vishwanath, T. Comyn, R.G. Mira, C. Brossier, C. Pascual-Caro, M. Faour, K. Boumendil, C. Chintaluri, C. Ramon-Duaso, R. Fan, K. Ghosh, H. Farrants, J.-P. Berwick, R. Sivakumar, M. Lopez-Manzaneda, E.R. Schreiter, T. Preat, T.P. Vogels, V. Rangaraju, A. Busquets-Garcia, P.-Y. Plaçais, A. Pavlowsky, J. de Juan-Sanz, Nature Metabolism 8 (2026) 467–488.","apa":"Amrapali Vishwanath, A., Comyn, T., Mira, R. G., Brossier, C., Pascual-Caro, C., Faour, M., … de Juan-Sanz, J. (2026). Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species. <i>Nature Metabolism</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s42255-026-01451-w\">https://doi.org/10.1038/s42255-026-01451-w</a>","ama":"Amrapali Vishwanath A, Comyn T, Mira RG, et al. Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species. <i>Nature Metabolism</i>. 2026;8(2):467-488. doi:<a href=\"https://doi.org/10.1038/s42255-026-01451-w\">10.1038/s42255-026-01451-w</a>","ieee":"A. Amrapali Vishwanath <i>et al.</i>, “Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species,” <i>Nature Metabolism</i>, vol. 8, no. 2. Springer Nature, pp. 467–488, 2026.","mla":"Amrapali Vishwanath, Anjali, et al. “Mitochondrial Ca2+ Efflux Controls Neuronal Metabolism and Long-Term Memory across Species.” <i>Nature Metabolism</i>, vol. 8, no. 2, Springer Nature, 2026, pp. 467–88, doi:<a href=\"https://doi.org/10.1038/s42255-026-01451-w\">10.1038/s42255-026-01451-w</a>."},"page":"467-488","file_date_updated":"2026-03-02T15:21:27Z","scopus_import":"1"}