{"department":[{"_id":"TiVo"}],"abstract":[{"lang":"eng","text":"So-called spontaneous activity is a central hallmark of most nervous systems. Such non-causal firing is contrary to the tenet of spikes as a means of communication, and its purpose remains unclear. We propose that self-initiated firing can serve as a release valve to protect neurons from the toxic conditions arising in mitochondria from lower-than-baseline energy consumption. To demonstrate the viability of our hypothesis, we built a set of models that incorporate recent experimental results indicating homeostatic control of metabolic products—Adenosine triphosphate (ATP), adenosine diphosphate (ADP), and reactive oxygen species (ROS)—by changes in firing. We explore the relationship of metabolic cost of spiking with its effect on the temporal patterning of spikes and reproduce experimentally observed changes in intrinsic firing in the fruitfly dorsal fan-shaped body neuron in a model with ROS-modulated potassium channels. We also show that metabolic spiking homeostasis can produce indefinitely sustained avalanche dynamics in cortical circuits. Our theory can account for key features of neuronal activity observed in many studies ranging from ion channel function all the way to resting state dynamics. We finish with a set of experimental predictions that would confirm an integrated, crucial role for metabolically regulated spiking and firmly link metabolic homeostasis and neuronal function."}],"publication_status":"published","date_published":"2023-11-21T00:00:00Z","issue":"48","article_processing_charge":"Yes (in subscription journal)","month":"11","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_updated":"2023-12-11T12:47:41Z","pmid":1,"file":[{"content_type":"application/pdf","access_level":"open_access","creator":"dernst","file_name":"2023_PNAS_Chintaluri.pdf","checksum":"bf4ec38602a70dae4338077a5a4d497f","relation":"main_file","success":1,"file_id":"14678","date_created":"2023-12-11T12:45:12Z","file_size":16891602,"date_updated":"2023-12-11T12:45:12Z"}],"type":"journal_article","day":"21","title":"Metabolically regulated spiking could serve neuronal energy homeostasis and protect from reactive oxygen species","quality_controlled":"1","related_material":{"link":[{"relation":"software","url":"https://github.com/ccluri/metabolic_spiking"}]},"status":"public","publisher":"National Academy of Sciences","scopus_import":"1","oa":1,"oa_version":"None","date_created":"2023-12-10T23:01:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"_id":"14666","article_number":"e2306525120","article_type":"original","citation":{"short":"C. Chintaluri, T.P. Vogels, Proceedings of the National Academy of Sciences of the United States of America 120 (2023).","ama":"Chintaluri C, Vogels TP. Metabolically regulated spiking could serve neuronal energy homeostasis and protect from reactive oxygen species. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2023;120(48). doi:<a href=\"https://doi.org/10.1073/pnas.2306525120\">10.1073/pnas.2306525120</a>","apa":"Chintaluri, C., &#38; Vogels, T. P. (2023). Metabolically regulated spiking could serve neuronal energy homeostasis and protect from reactive oxygen species. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2306525120\">https://doi.org/10.1073/pnas.2306525120</a>","chicago":"Chintaluri, Chaitanya, and Tim P Vogels. “Metabolically Regulated Spiking Could Serve Neuronal Energy Homeostasis and Protect from Reactive Oxygen Species.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2023. <a href=\"https://doi.org/10.1073/pnas.2306525120\">https://doi.org/10.1073/pnas.2306525120</a>.","ista":"Chintaluri C, Vogels TP. 2023. Metabolically regulated spiking could serve neuronal energy homeostasis and protect from reactive oxygen species. Proceedings of the National Academy of Sciences of the United States of America. 120(48), e2306525120.","ieee":"C. Chintaluri and T. P. Vogels, “Metabolically regulated spiking could serve neuronal energy homeostasis and protect from reactive oxygen species,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 120, no. 48. National Academy of Sciences, 2023.","mla":"Chintaluri, Chaitanya, and Tim P. Vogels. “Metabolically Regulated Spiking Could Serve Neuronal Energy Homeostasis and Protect from Reactive Oxygen Species.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 120, no. 48, e2306525120, National Academy of Sciences, 2023, doi:<a href=\"https://doi.org/10.1073/pnas.2306525120\">10.1073/pnas.2306525120</a>."},"external_id":{"pmid":["37988463"]},"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"doi":"10.1073/pnas.2306525120","author":[{"last_name":"Chintaluri","first_name":"Chaitanya","full_name":"Chintaluri, Chaitanya","id":"E4EDB536-3485-11EA-98D2-20AF3DDC885E"},{"orcid":"0000-0003-3295-6181","first_name":"Tim P","last_name":"Vogels","full_name":"Vogels, Tim P","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425"}],"has_accepted_license":"1","publication":"Proceedings of the National Academy of Sciences of the United States of America","ddc":["570"],"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"}],"acknowledgement":"We thank Prof. C. Nazaret and Prof. J.-P. Mazat for sharing the code of their mitochondrial model. We also thank G. Miesenböck, E. Marder, L. Abbott, A. Kempf, P. Hasenhuetl, W. Podlaski, F. Zenke, E. Agnes, P. Bozelos, J. Watson, B. Confavreux, and G. Christodoulou, and the rest of the Vogels Lab for their feedback. This work was funded by Wellcome Trust and Royal Society Sir Henry Dale Research Fellowship (WT100000), a Wellcome Trust Senior Research Fellowship (214316/Z/18/Z), and a UK Research and Innovation, Biotechnology and Biological Sciences Research Council grant (UKRI-BBSRC BB/N019512/1).","file_date_updated":"2023-12-11T12:45:12Z","year":"2023","intvolume":"       120","volume":120}