{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:32Z","timestamp":1787005772740,"version":"build-2736575974"},"reference-count":79,"publisher":"National Academy of Sciences","issue":"28","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 NS132156"],"award-info":[{"award-number":["R35 NS132156"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:p>\n                    Glycogen is the largest energy reserve in the brain, but the specific role of glycogen in supporting neuronal energy metabolism in vivo is not well understood. We established a system in\n                    <jats:italic toggle=\"yes\">Caenorhabditis elegans<\/jats:italic>\n                    to dynamically probe glycolytic states in single cells of living animals via the use of the glycolytic sensor HYlight and determined that neurons can dynamically regulate glycolysis in response to activity or transient hypoxia. We performed an RNAi screen and identified that PYGL-1, an ortholog of the human glycogen phosphorylase, is required in neurons for glycolytic plasticity. We determined that neurons employ at least two mechanisms of glycolytic plasticity: glycogen-dependent glycolytic plasticity (GDGP) and glycogen-independent glycolytic plasticity. We uncover that GDGP is employed under conditions of mitochondrial dysfunction, such as transient hypoxia or in mutants for mitochondrial function. We find that the loss of GDGP impairs glycolytic plasticity and is associated with defects in synaptic vesicle recycling during hypoxia. Together, our study reveals that, in vivo, neurons can directly use glycogen as a fuel source to sustain glycolytic plasticity and synaptic function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2509003122","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:26:22Z","timestamp":1752161182000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Glycogen supports glycolytic plasticity in neurons"],"prefix":"10.1073","volume":"122","author":[{"given":"Milind","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Neuroscience","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Department of Cell Biology","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute","place":["New Haven"]},{"name":"Center for Neurodevelopment and Plasticity","place":["New Haven"]},{"name":"Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4926-5064","authenticated-orcid":false,"given":"Aaron D.","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Department of Neuroscience","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Department of Cell Biology","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute","place":["New Haven"]},{"name":"Center for Neurodevelopment and Plasticity","place":["New Haven"]},{"name":"Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali A.","family":"Vishwanath","sequence":"additional","affiliation":[{"name":"Department of Neuroscience","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Department of Cell Biology","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute","place":["New Haven"]},{"name":"Center for Neurodevelopment and Plasticity","place":["New Haven"]},{"name":"Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Tsives","sequence":"additional","affiliation":[{"name":"Department of Neuroscience","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Department of Cell Biology","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute","place":["New Haven"]},{"name":"Center for Neurodevelopment and Plasticity","place":["New Haven"]},{"name":"Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Neuroscience","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Department of Cell Biology","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute","place":["New Haven"]},{"name":"Center for Neurodevelopment and Plasticity","place":["New Haven"]},{"name":"Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Emerson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Department of Cell Biology","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute","place":["New Haven"]},{"name":"Center for Neurodevelopment and Plasticity","place":["New Haven"]},{"name":"Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Goodman","sequence":"additional","affiliation":[{"name":"Department of Neuroscience","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Department of Cell Biology","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute","place":["New Haven"]},{"name":"Center for Neurodevelopment and Plasticity","place":["New Haven"]},{"name":"Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Col\u00f3n-Ramos","sequence":"additional","affiliation":[{"name":"Department of Neuroscience","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Department of Cell Biology","place":["New Haven"]},{"name":"Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute","place":["New Haven"]},{"name":"Center for Neurodevelopment and Plasticity","place":["New Haven"]},{"name":"Yale University","place":["New Haven"]},{"name":"Marine Biological Laboratory Fellow","place":["Woods Hole"]},{"name":"Marine Biological Laboratory","place":["Woods Hole"]},{"name":"Instituto de Neurobiolog\u00eda","place":["San Juan"]},{"name":"Recinto de Ciencias M\u00e9dicas","place":["San Juan"]},{"name":"Universidad de Puerto Rico","place":["San Juan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200110000-00001"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00062.2017"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010459107"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1900-6"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nic.2006.08.001"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-071516-044450"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncom.2019.00049"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1989.62.4.882"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2013.06.018"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1088\/1757-899X\/301\/1\/012022"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.06.021"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2314699121"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14829"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16032"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.042"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00216"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.03.035"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695810"},{"key":"e_1_3_5_19_2","doi-asserted-by":"crossref","unstructured":"P. Shetty F. Galeffi D. Turner Cellular Links between Neuronal Activity and Energy Homeostasis (Frontiers in Pharmacology Series 2012) vol. 3.","DOI":"10.3389\/fphar.2012.00043"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201803152"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.293af.x"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0251-4"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2000.03225.x"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00606-x"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2018.19"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.12.020"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112566"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.016"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20111416"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R117.802843"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.200"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00374"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02055-5"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20377"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201807127"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-27480-1_10"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.33"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1998"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00431"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204407119"},{"key":"e_1_3_5_41_2","doi-asserted-by":"crossref","unstructured":"A. C. Miller T. R. Thiele S. Faumont M. L. Moravec S. R. Lockery Step-response analysis of chemotaxis in Caenorhabditis elegans. J. Neurosci. 25 3369\u20133378 (2005).","DOI":"10.1523\/JNEUROSCI.5133-04.2005"},{"key":"e_1_3_5_42_2","doi-asserted-by":"crossref","unstructured":"D. R. Albrecht C. I. Bargmann High-content behavioral analysis of Caenorhabditis elegans in precise spatiotemporal chemical environments. Nat. Methods 8 599\u2013605 (2011).","DOI":"10.1038\/nmeth.1630"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2020.08.002"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.283895.116"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.03.016"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007559"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003921"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/72850"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00579-5"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2015.09.002"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.07.042"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202357440"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0844"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14235912"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.07.006"},{"key":"e_1_3_5_56_2","doi-asserted-by":"crossref","unstructured":"X. Li Systems-level design principles of metabolic rewiring in an animal. Nature 640 203\u2013211 (2025).","DOI":"10.1038\/s41586-025-08636-5"},{"key":"e_1_3_5_57_2","doi-asserted-by":"crossref","unstructured":"S. R. Taylor Molecular topography of an entire nervous system. Cell 184 4329\u20134347.e23 (2021).","DOI":"10.1016\/j.cell.2021.06.023"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1611-17.2018"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80944-7"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06927"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.03.011"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00071-5"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1143762"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.03.054"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200319010"},{"key":"e_1_3_5_66_2","doi-asserted-by":"crossref","unstructured":"K. Mann S. Deny S. Ganguli T. R. Clandinin Coupling of activity metabolism and behaviour across the Drosophila brain. Nature 593 244\u2013248 (2021).","DOI":"10.1038\/s41586-021-03497-0"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.656405"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.11.020"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn6016"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.64821"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81645"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclnm.2011.01.005"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228767"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70092-9"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02421.x"},{"key":"e_1_3_5_76_2","doi-asserted-by":"publisher","DOI":"10.1042\/AN20120021"},{"key":"e_1_3_5_77_2","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20190041"},{"key":"e_1_3_5_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2017.09.007"},{"key":"e_1_3_5_79_2","unstructured":"A. D. Wolfe M. Singh Singh2025_data. Github. https:\/\/doi.org\/10.5281\/zenodo.15742216. Accessed 25 June 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2509003122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T20:49:24Z","timestamp":1753130964000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2509003122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":79,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2025,7,15]]}},"alternative-id":["10.1073\/pnas.2509003122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2509003122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]},"assertion":[{"value":"2025-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2509003122"}}