--- _id: '14666' 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. 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). article_number: e2306525120 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Chaitanya full_name: Chintaluri, Chaitanya id: E4EDB536-3485-11EA-98D2-20AF3DDC885E last_name: Chintaluri - first_name: Tim P full_name: Vogels, Tim P id: CB6FF8D2-008F-11EA-8E08-2637E6697425 last_name: Vogels orcid: 0000-0003-3295-6181 citation: ama: Chintaluri C, Vogels TP. 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. 2023;120(48). doi:10.1073/pnas.2306525120 apa: Chintaluri, C., & Vogels, T. P. (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. National Academy of Sciences. https://doi.org/10.1073/pnas.2306525120 chicago: Chintaluri, Chaitanya, and Tim P Vogels. “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. National Academy of Sciences, 2023. https://doi.org/10.1073/pnas.2306525120. ieee: C. Chintaluri and T. P. Vogels, “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, vol. 120, no. 48. National Academy of Sciences, 2023. 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. mla: Chintaluri, Chaitanya, and Tim P. Vogels. “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, vol. 120, no. 48, e2306525120, National Academy of Sciences, 2023, doi:10.1073/pnas.2306525120. short: C. Chintaluri, T.P. Vogels, Proceedings of the National Academy of Sciences of the United States of America 120 (2023). date_created: 2023-12-10T23:01:00Z date_published: 2023-11-21T00:00:00Z date_updated: 2023-12-11T12:47:41Z day: '21' ddc: - '570' department: - _id: TiVo doi: 10.1073/pnas.2306525120 external_id: pmid: - '37988463' file: - access_level: open_access checksum: bf4ec38602a70dae4338077a5a4d497f content_type: application/pdf creator: dernst date_created: 2023-12-11T12:45:12Z date_updated: 2023-12-11T12:45:12Z file_id: '14678' file_name: 2023_PNAS_Chintaluri.pdf file_size: 16891602 relation: main_file success: 1 file_date_updated: 2023-12-11T12:45:12Z has_accepted_license: '1' intvolume: ' 120' issue: '48' language: - iso: eng month: '11' oa: 1 oa_version: None pmid: 1 project: - _id: c084a126-5a5b-11eb-8a69-d75314a70a87 grant_number: 214316/Z/18/Z name: What’s in a memory? Spatiotemporal dynamics in strongly coupled recurrent neuronal networks. publication: Proceedings of the National Academy of Sciences of the United States of America publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - relation: software url: https://github.com/ccluri/metabolic_spiking scopus_import: '1' status: public title: Metabolically regulated spiking could serve neuronal energy homeostasis and protect from reactive oxygen species tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 120 year: '2023' ...