Molecular diversity of corticotropin-releasing hormone mRNA-containing neurons in the hypothalamus

    1. Tibor Harkany1,4
    1. 1Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria
    2. 2MTA-SE NAP Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, Budapest, Hungary
    3. 3Department of Anatomy, Semmelweis University, Budapest, Hungary
    4. 4Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    1. Correspondence should be addressed to R A Romanov or T Harkany; Email: Roman.Romanov{at} or Tibor.Harkany{at}


    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.

    • Received 23 November 2016
    • Accepted 4 January 2017
    • Made available online as an Accepted Preprint 5 January 2017
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