title: Molecular diversity of corticotropin-releasing hormone mRNA-containing neurons in the hypothalamus.
abstract: Hormonal responses to acute stress rely on the rapid induction of corticotropin-releasing hormone (CRH) production in the mammalian hypothalamus, with subsequent instructive steps culminating in corticosterone release at the periphery. Hypothalamic CRH neurons in the paraventricular nucleus of the hypothalamus are therefore considered as 'stress neurons'. However, significant morphological and functional diversity among neurons that can transiently produce CRH in other hypothalamic nuclei has been proposed, particularly as histochemical and molecular biology evidence associates CRH to both GABA and glutamate neurotransmission. Here, we review recent advances through single-cell RNA sequencing and circuit mapping to suggest that CRH production reflects a state switch in hypothalamic neurons and thus confers functional competence rather than being an identity mark of phenotypically segregated neurons. We show that CRH mRNA transcripts can therefore be seen in GABAergic, glutamatergic and dopaminergic neuronal contingents in the hypothalamus. We then distinguish 'stress neurons' of the paraventricular nucleus that constitutively express secretagogin, a Ca2+sensor critical for the stimulus-driven assembly of the molecular machinery underpinning the fast regulated exocytosis of CRH at the median eminence. Cumulatively, we infer that CRH neurons are functionally and molecularly more diverse than previously thought.
authors.affiliation: Department of Molecular NeurosciencesCenter for Brain Research, Medical University of Vienna, Vienna, Austria Roman.Romanov@meduniwien.ac.at Tibor.Harkany@meduniwien.ac.at.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Romanov
authors.affiliation: MTA-SE NAP Research Group of Experimental Neuroanatomy and Developmental BiologyHungarian Academy of Sciences, Budapest, Hungary.|Department of AnatomySemmelweis University, Budapest, Hungary.
authors.forename: Alán
authors.initials: A
authors.lastname: Alpár
authors.affiliation: Department of NeuroscienceKarolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.affiliation: Department of Molecular NeurosciencesCenter for Brain Research, Medical University of Vienna, Vienna, Austria Roman.Romanov@meduniwien.ac.at Tibor.Harkany@meduniwien.ac.at.|Department of NeuroscienceKarolinska Institutet, Stockholm, Sweden.
authors.forename: Tibor
authors.initials: T
authors.lastname: Harkany
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D012333:RNA, Messenger
chemical_list: D012333:RNA, Messenger; D018698:Glutamic Acid; D003346:Corticotropin-Releasing Hormone
keywords: calcium-binding proteins; neuronal heterogeneity; single-cell RNA-sequencing; stress