Knockout of histamine receptor H3 alters adaptation to sudden darkness and monoamine levels in the zebrafish

Puttonen, Henri; Sundvik, Maria; Semenova, Svetlana; Shirai, Yukako; Chen, Yu‐Chia; Panula, Pertti

doi:10.1111/apha.12981

Cited by 13 publications

(22 citation statements)

References 77 publications

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“…Mouse and human expression analyses have shown that the mammalian histamine H3 receptor is expressed in the cerebral cortex, thalamus, hypothalamus, basal ganglia, hippocampus and amygdala 6 . In zebrafish larvae and juveniles, strong hrh3 expression has been observed in the telencephalon, with moderate expression levels in the hypothalamus, thalamus and optic tectum 25 . To assess the potential role of the hrh3 receptor in aggression, we first mapped hrh3 distribution in the adult zebrafish brain (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…To assess the potential role of the hrh3 receptor in aggression, we first mapped hrh3 distribution in the adult zebrafish brain (Figure 1). Similar to larvae and juveniles, 25 hrh3 expression is limited to discrete brain areas and cell populations with the strongest expression in the telencephalon. Dorsal telencephalic subregions showed very strong signals, especially in the medial and lateral zone of the dorsal telencephalic area (Dm and Dl; Figure 1A‐C), regions that are considered homologous to the mammalian amygdala and hippocampus respectively 26 .…”

Section: Resultsmentioning

confidence: 99%

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The zebrafish histamine H3 receptor modulates aggression, neural activity and forebrain functional connectivity

et al. 2020

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Aim Aggression is a behavioural trait characterized by the intention to harm others for offensive or defensive purposes. Neurotransmitters such as serotonin and dopamine are important mediators of aggression. However, the physiological role of the histaminergic system during this behaviour is currently unclear. Here, we aimed to better understand histaminergic signalling during aggression by characterizing the involvement of the histamine H3 receptor (Hrh3). Methods We have generated a novel zebrafish Hrh3 null mutant line using CRISPR‐Cas9 genome engineering and investigated behavioural changes and alterations to neural activity using whole brain Ca2+ imaging in zebrafish larvae and ribosomal protein S6 (rpS6) immunohistochemistry in adults. Results We show that genetic inactivation of the histamine H3 receptor (Hrh3) reduces aggression in zebrafish, an effect that can be reproduced by pharmacological inhibition. In addition, hrh3−/− zebrafish show behavioural impairments consistent with heightened anxiety. Larval in vivo whole brain Ca2+ imaging reveals higher neuronal activity in the forebrain of mutants, but lower activity in specific hindbrain areas and changes in measures of functional connectivity between subregions. Adult hrh3−/− zebrafish display brain region‐specific neural activity changes in response to aggression of both key regions of the social decision‐making network, and the areas containing histaminergic neurons in the zebrafish brain. Conclusion These results highlight the importance of zebrafish Hrh3 signalling for aggression and anxiety and uncover the brain areas involved. Targeting this receptor might be a potential novel therapeutic route for human conditions characterized by heightened aggression.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The zebrafish histamine H3 receptor modulates aggression, neural activity and forebrain functional connectivity

et al. 2020

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“…Genetic approaches for the modelling of physiological mechanisms, but also of human diseases, are mirrored by numerous publications in Acta Physiologica (Oxf.) . Genetically induced alterations of proteins such as membrane receptors or ion channels have been applied to evaluate the contribution of the respective protein to the normal physiological function, or its potential role in the pathogenesis of diseases .…”

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“…. Genetically induced alterations of proteins such as membrane receptors or ion channels have been applied to evaluate the contribution of the respective protein to the normal physiological function, or its potential role in the pathogenesis of diseases . The combination of more traditional physiological models with genetic models opened up new possibilities in research .…”

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Patzak

Ludwig

2019

Acta Physiologica

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“…Puttonen et al (this issue) report behavioural features and abnormalities of zebrafish lacking the histamine H3 receptor, which regulates the release of several neurotransmitters, including GABA, glutamate, histamine, serotonin, noradrenaline and dopamine . Despite normal morphological development, mutant larvae show faster locomotor adaptation to sudden darkness than control larvae, whereas there are no differences in basic locomotor activity during daytime and night.…”

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Fishing for histamine H3 receptor functions

Haas

2017

Acta Physiologica

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, P. 2017. Knockout of histamine receptor H3 alters adaptation to sudden darkness and monoamine levels in the zebrafish. Acta Physiol 222, e12981.Puttonen et al (this issue) report behavioural features and abnormalities of zebrafish lacking the histamine H3 receptor, which regulates the release of several neurotransmitters, including GABA, glutamate, histamine, serotonin, noradrenaline and dopamine.1 Despite normal morphological development, mutant larvae show faster locomotor adaptation to sudden darkness than control larvae, whereas there are no differences in basic locomotor activity during daytime and night. Zebrafish sleep, defined by immobility for a period of longer than 1 minute, is normal in hrh3 KO larvae. Adult hrh3 KO fish are hypoactive in comparison with control fish. Levels of dopamine and serotonin are reduced in the mutant larvae, suggesting that, also in zebrafish, hrh3 controls several transmitter systems. mRNA levels of major catecholamine-and serotonin-synthesizing enzymes and transporters are normal. Zebrafish now offers a valuable tool for comprehensive analysis of the neural basis of behaviour. As the fish has the same neurotransmitters as mammals, and many receptors are also shared, it is possible to address fundamental questions related to not only simple behaviours, but also complex social behaviour and disease mechanisms.Genome modification using the CRISPR/Cas9 methodology was used in this study. This new method has largely replaced previous forward and reverse genetic techniques also in the zebrafish. As zebrafish develop very rapidly after fertilization, transient translation inhibition using morpholino oligonucleotides has been a popular and successful approach to study functional roles of proteins encoded by specific genes. Morpholino oligonucleotides are demanding to use to inhibit translation of specific mRNAs because of several possible off-target effects, and recent guidelines suggest the use only in association with mutant fish and with extensive controls.2

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Knockout of histamine receptor H3 alters adaptation to sudden darkness and monoamine levels in the zebrafish

Cited by 13 publications

References 77 publications

The zebrafish histamine H3 receptor modulates aggression, neural activity and forebrain functional connectivity

The zebrafish histamine H3 receptor modulates aggression, neural activity and forebrain functional connectivity

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Fishing for histamine H3 receptor functions

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