{"doi":"10.1111/j.1460-9568.2012.08057.x","title":"Convergent inputs from electrically and topographically distinct orexin cells to locus coeruleus and ventral tegmental area","abstract":"<jats:title>Abstract</jats:title><jats:p>Orexin/hypocretin (orx/hcrt) neurons are thought to ensure that reward‐seeking is accompanied by alertness, but the underlying circuit organization is unclear. Reports of differential regulation of lateral versus medial orx/hcrt cells produced a hypothesis of ‘efferent dichotomy’, in which lateral orx/hcrt cells innervate the ventral tegmental area (VTA) and control reward, while medial orx/hcrt cells innervate locus coeruleus (LC) and control arousal. Two distinct types of orx/hcrt cells also emerged from analysis of intrinsic and input‐driven single‐cell electrical activity. To examine the projections of these emerging orx/hcrt subtypes to LC and VTA, we injected retrograde tracer into these regions in the mouse brain <jats:italic>in vivo</jats:italic>, and then examined the properties of tracer‐containing orx/hcrt cells in hypothalamic slices. VTA‐ and LC‐projecting orx/hcrt cells were found across the entire orx/hcrt field, including the zona incerta, perifornical area, dorsomedial/anterior and lateral hypothalamus. Within these areas, orx/hcrt cells had similar probabilities of projecting to VTA or LC. Examination of lateral versus medial sections revealed that VTA and LC received inputs from both lateral and medial orx/hcrt cells, but, unexpectedly, lateral orx/hcrt cells were more likely to project to LC than medial orx/hcrt cells. Finally, patch‐clamp recordings revealed that VTA and LC received projections from both electrical classes of orx/hcrt cells, which had similar likelihoods of projecting to VTA or LC. Contrary to previous predictions, our data suggest that medial and lateral orx/hcrt cells, and the different electrical and morphological subclasses of orx/hcrt cells identified to date, send projections to both LC and VTA.</jats:p>","journal":"European Journal of Neuroscience","year":2012,"id":627256,"datarank":0.62147020895873,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":0.0,"self_endowment_contribution":0.62147020895873,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1623283,"name":"Lise T. 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Reports of differential regulation of lateral versus medial orx/hcrt cells produced a hypothesis of ‘efferent dichotomy’, in which lateral orx/hcrt cells innervate the ventral tegmental area (VTA) and control reward, while medial orx/hcrt cells innervate locus coeruleus (LC) and control arousal. Two distinct types of orx/hcrt cells also emerged from analysis of intrinsic and input‐driven single‐cell electrical activity. To examine the projections of these emerging orx/hcrt subtypes to LC and VTA, we injected retrograde tracer into these regions in the mouse brain <jats:italic>in vivo</jats:italic>, and then examined the properties of tracer‐containing orx/hcrt cells in hypothalamic slices. VTA‐ and LC‐projecting orx/hcrt cells were found across the entire orx/hcrt field, including the zona incerta, perifornical area, dorsomedial/anterior and lateral hypothalamus. Within these areas, orx/hcrt cells had similar probabilities of projecting to VTA or LC. Examination of lateral versus medial sections revealed that VTA and LC received inputs from both lateral and medial orx/hcrt cells, but, unexpectedly, lateral orx/hcrt cells were more likely to project to LC than medial orx/hcrt cells. Finally, patch‐clamp recordings revealed that VTA and LC received projections from both electrical classes of orx/hcrt cells, which had similar likelihoods of projecting to VTA or LC. Contrary to previous predictions, our data suggest that medial and lateral orx/hcrt cells, and the different electrical and morphological subclasses of orx/hcrt cells identified to date, send projections to both LC and VTA.</jats:p>","is_dataset_classified":null,"base_score":4.143134726391533,"endowment":4.143134726391533,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22507526","pmcid":"PMC5767120","openalex_id":"https://openalex.org/W2168736159","authors":[],"funders":[{"funder_name":"Medical Research Council","grant_id":"G1000800I","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UP_1202/2","title":null},{"funder_name":"European Commission","grant_id":"200500","title":"Orchestration of instinctive drives"}],"total_grants":3,"fwci":2.5688,"citation_percentile":0.89766012,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":3},{"year":2014,"count":7},{"year":2015,"count":5},{"year":2016,"count":5},{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":4},{"year":2020,"count":6},{"year":2021,"count":6},{"year":2022,"count":4},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":5},{"year":2026,"count":1}],"oa_status":"closed","license":"Wiley Online Library User Agreement","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1460-9568.2012.08057.x","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1460-9568.2012.08057.x","host_type":"publisher"},{"url":"https://doi.org/10.1111/j.1460-9568.2012.08057.x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22507526","host_type":"repository"},{"url":"http://discovery.ucl.ac.uk/1414499/","host_type":"repository"},{"url":"http://discovery.ucl.ac.uk/1414650/","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5767120","host_type":"repository"},{"url":"https://kclpure.kcl.ac.uk/portal/en/publications/3a2540f0-68bb-4da5-874b-94799b747cdc","host_type":"repository"},{"url":"https://pure.au.dk/portal/en/publications/fa3dcd9d-ba30-48d4-be34-d12b7d9a33ad","host_type":""},{"url":"https://europepmc.org/articles/pmc5767120?pdf=render","host_type":""},{"url":"http://dx.doi.org/10.1111/j.1460-9568.2012.08057.x","host_type":""},{"url":"https://dx.doi.org/10.1111/j.1460-9568.2012.08057.x","host_type":""},{"url":"http://dx.doi.org/10.1111/j.1460-9568.2012.08057.x.","host_type":""},{"url":"https://doi.org/https://doi.org/10.1111/j.1460-9568.2012.08057.x","host_type":""}],"fields_of_study":["Sleep and Wakefulness Research","Circadian rhythm and melatonin","Sleep and related disorders","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Brain Mapping","Cell Count","Green Fluorescent Proteins","Hypothalamus","In Vitro Techniques","Inhibitory Postsynaptic Potentials","Intracellular Signaling Peptides and Proteins","Locus Coeruleus","Mice","Mice, Transgenic","Microscopy, Confocal","Microspheres","Neural Pathways","Neurons","Neuropeptides","Orexins","Rhodamines","Ventral Tegmental Area"],"mesh_terms":["Orexins","Animals","Brain Mapping","Cell Count","Hypothalamus","Locus Coeruleus","Mice, Transgenic","Microspheres","Neural Pathways","Neurons","Neuropeptides","Rhodamines","Ventral Tegmental Area","Microscopy, Confocal","Intracellular Signaling Peptides and Proteins","Green Fluorescent Proteins","Mice","Inhibitory Postsynaptic Potentials","In Vitro Techniques"],"keywords":["Locus coeruleus","Ventral tegmental area","Neuroscience","Orexin","Psychology","Biology","Dopamine","Central nervous system","Neuropeptide","Dopaminergic","Neurons","Brain Mapping","Orexins","Microscopy, Confocal","Rhodamines","Green Fluorescent Proteins","Neuropeptides","Hypothalamus","Intracellular Signaling Peptides and Proteins","610","Cell Count","Mice, Transgenic","In Vitro Techniques","Microspheres","Mice","Inhibitory Postsynaptic Potentials","616","Neural Pathways","Animals"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T16:51:06.557799Z","pmid":null,"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":[]}