Abstract
Three of the four histamine receptors have been identified in zebrafish. Whereas only one histamine receptor 1 gene (hrh1) is known, two copies of histamine receptor 2 (hrh2a and hrh2b) have been identified. Although initially only one gene encoding for histamine receptor 3 (hrh3) was recognized in zebrafish, the genome database contains information for two more hrh3-like genes, whereas no genes corresponding for histamine receptor 4 with expression mainly in the immune system have been identified. Hrh1 and hrh3 show prominent uneven expression in the zebrafish brain, with the strongest expression in the dorsal telencephalon. Quantitatively significant expression of hrh1, hrh2, and hrh3 can also be found in several peripheral organs. Whereas antagonists of hrh1, hrh2, and hrh3 all affect the locomotor activity of zebrafish larvae, interpretation of the data is hampered by a lack of information on receptor binding and signaling characteristics. Zebrafish mutants lacking any of the three histamine receptors have shown modest behavioral phenotypes, possibly due to genetic compensation. None of the receptor mutant fish have shown significant sleep phenotypes. Adult zebrafish lacking hrh3 display decreased locomotor activity. The zebrafish histamine system shows significant life-long plasticity: presenilin 1 mutant zebrafish develop an abnormally large number of histamine neurons and increased thigmotaxis and anxiety-related phenotype. Overexpression of histidine decarboxylase (hdc) in larval zebrafish is associated with an increased number of hypocretin neurons, whereas translation inhibition of hdc or exposure to α-fluoromethylhistidine leads to decreased numbers of hypocretin neurons. Current pharmacological evidence suggests that this may be mediated by hrh1. Further studies using acute, e.g., pharmacogenetic or optogenetic manipulation of selected components of brain circuits, are required to understand the full range of physiological functions of zebrafish histamine receptors.
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References
Ahrens MB et al (2012) Brain-wide neuronal dynamics during motor adaptation in zebrafish. Nature 485(7399):471–477
Ahrens MB, Huang KH, Narayan S, Mensh BD, Engert F (2013) Two-photon calcium imaging during fictive navigation in virtual environments. Front Neural Circuits 7:104
Anichtchik OV, Rinne JO, Kalimo H, Panula P (2000) An altered histaminergic innervation of the substantia nigra in Parkinson’s disease. Exp Neurol 163(1):20–30
Anichtchik OV, Kaslin J, Peitsaro N, Scheinin M, Panula P (2004) Neurochemical and behavioural changes in zebrafish Danio rerio after systemic administration of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurochem 88(2):443–453
Burgess HA, Granato M (2007) Modulation of locomotor activity in larval zebrafish during light adaptation. J Exp Biol 210(Pt 14):2526–2539
Candy J, Collet C (2005) Two tyrosine hydroxylase genes in teleosts. Biochim Biophys Acta 1727(1):35–44
Chen YC, Priyadarshini M, Panula P (2009) Complementary developmental expression of the two tyrosine hydroxylase transcripts in zebrafish. Histochem Cell Biol 132(4):375–381
Chen YC et al (2016) A novel developmental role for dopaminergic signaling to specify hypothalamic neurotransmitter identity. J Biol Chem 291(42):21880–21892
Chen A, Singh C, Oikonomou G, Prober DA (2017) Genetic analysis of histamine signaling in larval zebrafish sleep. eNeuro 4(1):ENEURO.0286-16.2017
Chen YC, Baronio D, Semenova S, Abdurakhmanova S, Panula P (2020) Cerebral dopamine neurotrophic factor regulates multiple neuronal subtypes and behavior. J Neurosci 40(32):6146–6164
Cofiel LP, Mattioli R (2009) L-histidine enhances learning in stressed zebrafish. Braz J Med Biol Res 42(1):128–134
Ekstrom P, Holmqvist BI, Panula P (1995) Histamine-immunoreactive neurons in the brain of the teleost Gasterosteus aculeatus L. Correlation with hypothalamic tyrosine hydroxylase- and serotonin-immunoreactive neurons. J Chem Neuroanat 8(2):75–85
Elbaz I, Yelin-Bekerman L, Nicenboim J, Vatine G, Appelbaum L (2012) Genetic ablation of hypocretin neurons alters behavioral state transitions in zebrafish. J Neurosci 32(37):12961–12972
El-Brolosy MA et al (2019) Genetic compensation triggered by mutant mRNA degradation. Nature 568(7751):193–197
Eriksson KS, Peitsaro N, Karlstedt K, Kaslin J, Panula P (1998) Development of the histaminergic neurons and expression of histidine decarboxylase mRNA in the zebrafish brain in the absence of all peripheral histaminergic systems. Eur J Neurosci 10(12):3799–3812
Eriksson KS, Sergeeva O, Brown RE, Haas HL (2001) Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus. J Neurosci 21(23):9273–9279
Frick L, Rapanelli M, Abbasi E, Ohtsu H, Pittenger C (2016) Histamine regulation of microglia: gene-environment interaction in the regulation of central nervous system inflammation. Brain Behav Immun 57:326–337
Huang SB et al (2017) Intradiencephalon injection of histamine inhibited the recovery of locomotor function of spinal cord injured zebrafish. Biochem Biophys Res Commun 489(3):275–280
Inagaki N, Panula P, Yamatodani A, Wada H (1991) Organization of the histaminergic system in the brain of the teleost, Trachurus trachurus. J Comp Neurol 310(1):94–102
John J et al (2013) Greatly increased numbers of histamine cells in human narcolepsy with cataplexy. Ann Neurol 74(6):786–793
Kaslin J, Panula P (2001) Comparative anatomy of the histaminergic and other aminergic systems in zebrafish (Danio rerio). J Comp Neurol 440(4):342–377
Kaslin J, Nystedt JM, Ostergard M, Peitsaro N, Panula P (2004) The orexin/hypocretin system in zebrafish is connected to the aminergic and cholinergic systems. J Neurosci 24(11):2678–2689
Leung LC et al (2019) Neural signatures of sleep in zebrafish. Nature 571(7764):198–204
Mattioli R, Nelson CA, Huston JP, Spieler RE (1998) Conditioned place-preference analysis in the goldfish with the H1 histamine antagonist chlorpheniramine. Brain Res Bull 45(1):41–44
Neuhauss SC et al (1999) Genetic disorders of vision revealed by a behavioral screen of 400 essential loci in zebrafish. J Neurosci 19(19):8603–8615
Norton WH et al (2011) Modulation of Fgfr1a signaling in zebrafish reveals a genetic basis for the aggression-boldness syndrome. J Neurosci 31(39):13796–13807
Orger MB, de Polavieja GG (2017) Zebrafish behavior: opportunities and challenges. Annu Rev Neurosci 40:125–147
Panula P, Yang HY, Costa E (1984) Histamine-containing neurons in the rat hypothalamus. Proc Natl Acad Sci U S A 81(8):2572–2576
Panula P et al (2010) The comparative neuroanatomy and neurochemistry of zebrafish CNS systems of relevance to human neuropsychiatric diseases. Neurobiol Dis 40(1):46–57
Parmentier R et al (2002) Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J Neurosci 22(17):7695–7711
Parmentier R et al (2007) The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders. Biochem Pharmacol 73(8):1157–1171
Peitsaro N, Kaslin J, Anichtchik OV, Panula P (2003) Modulation of the histaminergic system and behaviour by alpha-fluoromethylhistidine in zebrafish. J Neurochem 86(2):432–441
Peitsaro N, Sundvik M, Anichtchik OV, Kaslin J, Panula P (2007) Identification of zebrafish histamine H1, H2 and H3 receptors and effects of histaminergic ligands on behavior. Biochem Pharmacol 73(8):1205–1214
Postlethwait JH et al (1998) Vertebrate genome evolution and the zebrafish gene map. Nat Genet 18(4):345–349
Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF (2006) Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci 26(51):13400–13410
Puttonen HAJ et al (2018) Knockout of histamine receptor H3 alters adaptation to sudden darkness and monoamine levels in the zebrafish. Acta Physiol (Oxf) 222(3):e12981
Reite OB (1972) Comparative physiology of histamine. Physiol Rev 52(3):778–819
Rinne JO et al (2002) Increased brain histamine levels in Parkinson’s disease but not in multiple system atrophy. J Neurochem 81(5):954–960
Rocha SM et al (2016) Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation. J Neuroinflammation 13(1):137
Sallinen V et al (2009) MPTP and MPP+ target specific aminergic cell populations in larval zebrafish. J Neurochem 108(3):719–731
Spieler RE, Nelson CA, Huston JP, Mattioli R (1999) Post-trial administration of H1 histamine receptor blocker improves appetitive reversal learning and memory in goldfish, Carassius auratus. Neurosci Lett 277(1):5–8
Sundvik M, Panula P (2012) The organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location and co-transmitters. J Comp Neurol 520(17):3827–3845
Sundvik M et al (2011) The histaminergic system regulates wakefulness and orexin/hypocretin neuron development via histamine receptor H1 in zebrafish. FASEB J 25(12):4338–4347
Sundvik M, Chen YC, Panula P (2013) Presenilin1 regulates histamine neuron development and behavior in zebrafish, danio rerio. J Neurosci 33(4):1589–1597
Taylor SL (1986) Histamine food poisoning: toxicology and clinical aspects. Crit Rev Toxicol 17(2):91–128
Valko PO et al (2013) Increase of histaminergic tuberomammillary neurons in narcolepsy. Ann Neurol 74(6):794–804
Zecharia AY et al (2012) GABAergic inhibition of histaminergic neurons regulates active waking but not the sleep-wake switch or propofol-induced loss of consciousness. J Neurosci 32(38):13062–13075
Zhdanova IV, Wang SY, Leclair OU, Danilova NP (2001) Melatonin promotes sleep-like state in zebrafish. Brain Res 903(1–2):263–268
Acknowledgements
Original studies were funded by the Academy of Finland, Sigrid Juselius Foundation, Jane and Aatos Erkko Foundation, Magnus Ehrnrooth’s Foundation, and Finska Läkaresällskapet. We thank Henri Koivula, BSc, for expert help with the zebrafish system and experiments.
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Panula, P., Chen, YC., Baronio, D., Lewis, S., Sundvik, M. (2021). The Histamine System in Zebrafish Brain: Organization, Receptors, and Behavioral Roles. In: Yanai, K., Passani, M.B. (eds) The Functional Roles of Histamine Receptors. Current Topics in Behavioral Neurosciences, vol 59. Springer, Cham. https://doi.org/10.1007/7854_2021_259
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DOI: https://doi.org/10.1007/7854_2021_259
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