{"doi":"10.3389/fendo.2022.875865","title":"Basal and Stress-Induced Network Activity in the Adrenal Medulla In Vivo","abstract":"<jats:p>The adrenal medulla plays a critical role in mammalian homeostasis and the stress response. It is populated by clustered chromaffin cells that secrete epinephrine or norepinephrine along with peptides into the bloodstream affecting distant target organs. Despite been heavily studied, the central control of adrenal medulla and <jats:italic>in-situ</jats:italic> spatiotemporal responsiveness remains poorly understood. For this work, we continuously monitored the electrical activity of individual adrenomedullary chromaffin cells in the living anesthetized rat using multielectrode arrays. We measured the chromaffin cell activity under basal and physiological stress conditions and characterized the functional micro-architecture of the adrenal medulla. Under basal conditions, chromaffin cells fired action potentials with frequencies between ~0.2 and 4 Hz. Activity was almost completely driven by sympathetic inputs coming through the splanchnic nerve. Chromaffin cells were organized into independent local networks in which cells fired in a specific order, with latencies from hundreds of microseconds to a few milliseconds. Electrical stimulation of the splanchnic nerve evoked almost exactly the same spatiotemporal firing patterns that occurred spontaneously. Hypoglycemic stress, induced by insulin administration resulted in increased activity of a subset of the chromaffin cells. In contrast, respiratory arrest induced by lethal anesthesia resulted in an increase in the activity of virtually all chromaffin cells before cessation of all activity. These results suggest a stressor-specific activation of adrenomedullary chromaffin cell networks and revealed a surprisingly complex electrical organization that likely reflects the dynamic nature of the adrenal medulla’s neuroendocrine output during basal conditions and during different types of physiological stress.</jats:p>","journal":"Frontiers in Endocrinology","year":2022,"id":25597,"datarank":0.5299944630553188,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.17031017213556313,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.17031017213556313,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":10,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":150205,"name":"Stephen A. Ernst","orcid":null,"position":1,"is_corresponding":false},{"id":150206,"name":"Ronald W. Holz","orcid":null,"position":2,"is_corresponding":false},{"id":150207,"name":"Edward L. Stuenkel","orcid":null,"position":3,"is_corresponding":false},{"id":150204,"name":"Jose R. Lopez Ruiz","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35795145","pmcid":"PMC9250985","openalex_id":"https://openalex.org/W4283166699","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"R01-170553, R01-097498","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01NS097498-07","title":"Trans-synaptic control of presynaptic neurotransmitter release"},{"funder_name":"Medical School, University of Michigan","grant_id":"","title":null}],"total_grants":3,"fwci":0.9085,"citation_percentile":0.69153894,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":1},{"year":2024,"count":6},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fendo.2022.875865/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fendo.2022.875865/pdf","host_type":"GOLD"},{"url":"https://www.frontiersin.org/articles/10.3389/fendo.2022.875865/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fendo.2022.875865/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fendo.2022.875865","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35795145","host_type":"repository"},{"url":"https://doaj.org/article/10a96504b0ca48bc9538d8064af23505","host_type":"repository"},{"url":"https://figshare.com/articles/journal_contribution/Basal_and_Stress-Induced_Network_Activity_in_the_Adrenal_Medulla_In_Vivo/25610205","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9250985","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9250985","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9250985?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3389/fendo.2022.875865","host_type":""}],"fields_of_study":["Neuropeptides and Animal Physiology","Receptor Mechanisms and Signaling","Ion channel regulation and function","Medicine","Biology","0301 basic medicine","0303 health sciences","03 medical and health sciences","Adrenal Medulla","Animals","Chromaffin Cells","Epinephrine","Mammals","Norepinephrine","Rats","Splanchnic Nerves"],"mesh_terms":["Adrenal Medulla","Animals","Epinephrine","Mammals","Norepinephrine","Splanchnic Nerves","Chromaffin Cells","Rats"],"keywords":["Adrenal medulla","Splanchnic nerves","Chromaffin cell","Internal medicine","Endocrinology","Sympathoadrenal system","Homeostasis","Catecholamine","Epinephrine","Stimulation","Medulla","Basal (medicine)","Biology","Splanchnic","Neuroscience","Medicine","Insulin","Hemodynamics","Electrophysiology","In-vivo","Stress response","Mammals","Chromaffin Cells","RC648-665","Diseases of the endocrine glands. 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