Fishing for histamine H3 receptor functions

Abstract

, 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

Histamine pharmacology: from Sir Henry Dale to the 21st century

“…The current knowledge of the histaminergic system and its interactions with other systems in the brain derives predominately from extensive studies in rodents, humans and the zebrafish, as summarized in a number of excellent reviews that are available in the literature (Haas and Panula, 2003; Haas et al ., 2008; Nuutinen and Panula, 2010; Sundvik and Panula, 2015; Nieto‐Alamilla et al ., 2016; Provensi et al ., 2018). In particular, the zebrafish has recently been shown to be a valuable tool for dissecting the role of histaminergic and histaminoceptive neurons in the brain by employing cutting‐edge methodologies, such as genome modification using the CRISPR/Cas9 editing tool (Haas, 2018).…”