Urocortins and their unfolding role in mammalian social behavior
- 97 Downloads
The corticotropin-releasing factor (CRF) system is well known for its major role in coordinating the endocrine, autonomic and behavioral responses to stress. These functions have been shown to be mediated mainly by the binding of the CRF neuropeptide to its specific receptor CRFR1. Yet, the CRF system comprises several more neuropeptides, including the three urocortins, UCN1, UCN2 and UCN3, of which the latter two bind specifically to a distinct receptor—CRFR2. Unlike the brain-wide abundant expression of CRF and CRFR1, the brain expression of the urocortins and CRFR2 is rather restricted and seems to be focused in limbic areas associated with social behavior. Here, we will review accumulating evidence from recent studies that unfold the role of UCN2 and UCN3 in regulating mammalian social behavior, via activation of CRFR2.
KeywordsUrocortins Social behavior CRF system CRFR2 Medial amygdala
I wish to thank Dr. Shai Netser for his help.
This research was supported by The Human Frontier Science Program (HFSP grant RGP0019/2015), the Israel Science Foundation (ISF grant #1361/17) and by the Ministry of Science, Technology and Space of Israel (Grant #3-12068).
- Ahern TH, Young LJ 2009 The impact of early life family structure on adult social attachment, alloparental behavior, and the neuropeptide systems regulating affiliative behaviors in the monogamous prairie vole (Microtus ochrogaster). Front Behav Neurosci 3Google Scholar
- Bosch OJ, Dabrowska J, Modi ME, Johnson ZV, Keebaugh AC, Barrett CE, Ahern TH, Guo J, Grinevich V, Rainnie DG, Neumann ID, Young LJ (2016) Oxytocin in the nucleus accumbens shell reverses CRFR2-evoked passive stress-coping after partner loss in monogamous male prairie voles. Psychoneuroendocrinology 64:66–78CrossRefGoogle Scholar
- Chen AM, Perrin MH, Digruccio MR, Vaughan JM, Brar BK, Arias CM, Lewis KA, Rivier JE, Sawchenko PE, Vale WW (2005) A soluble mouse brain splice variant of type 2alpha corticotropin-releasing factor (CRF) receptor binds ligands and modulates their activity. Proc Natl Acad Sci U S A 102:2620–2625CrossRefGoogle Scholar
- Dabrowska J, Hazra R, Ahern TH, Guo JD, McDonald AJ, Mascagni F, Muller JF, Young LJ, Rainnie DG (2011) Neuroanatomical evidence for reciprocal regulation of the corticotrophin-releasing factor and oxytocin systems in the hypothalamus and the bed nucleus of the stria terminalis of the rat: implications for balancing stress and affect. Psychoneuroendocrinology 36:1312–1326CrossRefGoogle Scholar
- Deussing J, Breu J, Binder EB, Ohl F, Holsboer F, Wurst W (2003) Addressing in vivo functions of urocortin III, a novel member of the CRH family of neuropeptides. Pharmacopsychiatry 36:221–221Google Scholar
- Deussing JM, Breu J, Kuhne C, Kallnik M, Bunck M, Glasl L, Yen YC, Schmidt MV, Zurmuhlen R, Vogl AM, Gailus-Durner V, Fuchs H, Holter SM, Wotjak CT, Landgraf R, de Angelis MH, Holsboer F, Wurst W (2010) Urocortin 3 modulates social discrimination abilities via corticotropin-releasing hormone receptor type 2. J Neurosci 30:9103–9116CrossRefGoogle Scholar
- Hostetler CM, Ryabinin AE, 2013. The CRF system and social behavior: a review. Front Neurosci-Switz 7Google Scholar
- Koolhaas JM, Bartolomucci A, Buwalda B, de Boer SF, Flugge G, Korte SM, Meerlo P, Murison R, Olivier B, Palanza P, Richter-Levin G, Sgoifo A, Steimer T, Stiedl O, van Dijk G, Wohr M, Fuchs E (2011) Stress revisited: a critical evaluation of the stress concept. Neurosci Biobehav Rev 35:1291–1301CrossRefGoogle Scholar
- Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko PE, Vale WW (2001) Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc Natl Acad Sci U S A 98:7570–7575CrossRefGoogle Scholar
- Lovett-Barron M, Andalman AS, Allen WE, Vesuna S, Kauvar I, Burns VM, Deisseroth K (2017) Ancestral circuits for the coordinated modulation of brain state. Cell 171(1411–1423):e1417Google Scholar
- Pournajafi-Nazarloo H, Partoo L, Sanzenbacher L, Paredes J, Hashimoto K, Azizi F, Sue Carter C (2009) Stress differentially modulates mRNA expression for corticotrophin-releasing hormone receptors in hypothalamus, hippocampus and pituitary of prairie voles. Neuropeptides 43:113–123CrossRefGoogle Scholar
- Reyes TM, Lewis K, Perrin MH, Kunitake KS, Vaughan J, Arias CA, Hogenesch JB, Gulyas J, Rivier J, Vale WW, Sawchenko PE (2001) Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc Natl Acad Sci U S A 98:2843–2848CrossRefGoogle Scholar
- Sawchenko PE, Swanson LW (1985) Localization, colocalization, and plasticity of corticotropin-releasing factor immunoreactivity in rat-brain. Fed Proc 44:221–227Google Scholar
- Shemesh Y, Forkosh O, Mahn M, Anpilov S, Sztainberg Y, Manashirov S, Shlapobersky T, Elliott E, Tabouy L, Ezra G, Adler ES, Ben-Efraim YJ, Gil S, Kuperman Y, Haramati S, Dine J, Eder M, Deussing JM, Schneidman E, Yizhar O, Chen A (2016) Ucn3 and CRF-R2 in the medial amygdala regulate complex social dynamics. Nat Neurosci 19:1489–1496CrossRefGoogle Scholar
- Vale W, Rivier C, Brown MR, Spiess J, Koob G, Swanson L, Bilezikjian L, Bloom F, Rivier J (1983) Chemical and biological characterization of corticotropin releasing factor. Recent Prog Horm Res 39:245–270Google Scholar