{"doi":"10.1113/jp286709","title":"Navigating the labyrinth of ganglionated plexi: unravelling the Minotaur's role in atrial fibrillation","abstract":"Despite significant progress in diagnosing and treating atrial fibrillation (AF), the underlying pathogenesis of this condition remains largely unknown. However, recent research has identified ganglionated plexi (GP) as key players in the initiation and maintenance of AF (Stavrakis et al., 2015). These complex networks of neurons within the autonomic nervous system have a profound impact on the electrical activity of the heart. To advance our understanding of AF pathogenesis and develop effective therapeutic strategies, it is crucial to delve deeper into the physiological properties of intracardiac nervous system (ICNS) neurons and their role in the development and progression of AF. The majority of the available tissue data come from animal studies, while human data are scarce (Stavrakis et al., 2015). In the current issue of the Journal of Physiology, Ashton et al. (2024) embarked on an innovative study to investigate the structural and functional properties of human autonomic neurons from the GP in patients with and without AF. By conducting heart biopsies and employing advanced electrophysiological and imaging techniques, the authors shed light on the complex interplay between GP neurons and their involvement in AF. The investigators are to be congratulated for this elegant mechanistic study that provides novel insights into the pathophysiology of AF and paves the way for potential prognostic biomarkers and therapeutic targets. The study begins by confirming the high anatomical complexity and extensive interconnections among neurons within and between GP. Through whole-cell patch clamp experiments, the authors show that GP neurons from AF patients have a lower stimulation threshold to fire an action potential, a finding which potentially explains the aberrant activity or increased excitability associated with AF pathogenesis (Chen et al., 2014). Additionally, the authors use confocal imaging to demonstrate a high density of synaptic input onto human GP neurons, particularly in AF patient tissue. This finding supports the potential for synaptic communication between networks of GP neurons and input from the extrinsic cardiac nervous system. However, it is important to note that recordings of synaptic activity are required to confirm this hypothesis. Furthermore, the authors quantified major neuron types within the GP and revealed remarkable differences between AF and non-AF patients. Interestingly, GP from AF patients exhibited a lower percentage of vesicular acetylcholine transporter (VAChT)-positive neurons, a higher percentage of tyrosine hydroxylase (TH)-positive neurons and fewer dual-phenotype neurons. While their study provides significant insights into the role of GP in AF, there are several areas that warrant further investigation. The authors have elegantly characterized the differences in cholinergic and noradrenergic neurons between AF and non-AF patients. However, there is a need for additional research to elucidate the specific GP subtypes (Kim et al., 2018) and their role in AF pathogenesis. Additionally, exploring the involvement of other neuropeptides and neurotransmitters such as neuropeptide Y and S100B in the context of AF could provide a more comprehensive understanding of the disease. Understanding the heterogeneity within GP and the involvement of neuropeptides and neurotransmitters in the pathogenesis of AF has the potential to yield new prognostic biomarkers and therapeutic targets for patients with AF. Therefore, progress in this domain is crucial for enhancing our understanding of the disease and improving patient care. Moreover, it is important to consider that despite GP constituting an interconnected network of neurons, GP in specific anatomical locations exert control over distinct regions of the heart. The study focuses on the right atrial ganglionated plexus (RAGP) which is known to primarily influence sinoatrial node function (Hanna et al., 2021). Therefore, caution should be exercised when","journal":"The Journal of Physiology","year":2024,"id":498294,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240658,"name":"Stavros Stavrakis","orcid":"0000-0002-4370-8135","position":1,"is_corresponding":false},{"id":860139,"name":"Stefanos Zafeiropoulos","orcid":"0000-0002-3284-2515","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-19T02:09:38.543544Z","pmid":"38848122","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}