Organization of the histaminergic system in adult zebrafish (Danio rerio) brain: Neuron number, location, and cotransmitters

Abstract

Histamine is an essential factor in the ascending arousal system (AAS) during motivated behaviors. Histamine and hypocretin/orexin (hcrt) are proposed to be responsible for different aspects of arousal and wakefulness, histamine mainly for cognitive and motivated behaviors. In this study we visualized the entire histaminergic neuron population in adult male and female zebrafish brain and quantified the histaminergic neuron numbers. There were 40-45 histaminergic neurons in both male and female zebrafish brain. Further, we identified cotransmitters of histaminergic neurons in the ventrocaudal hypothalamus, i.e., around the posterior recess (PR) in adult zebrafish. Galanin, γ-aminobutyric acid (GABA), and thyrotropin-releasing hormone (TRH) were colocalized with histamine in some but not all neurons, a result that was verified by intracerebroventricular injections of colchicine into adult zebrafish. Fibers immunoreactive (ir) for galanin, GABA, TRH, or methionine-enkephalin (mENK) were dense in the ventrocaudal hypothalamus around the histaminergic neurons. In histamine-ir fibers TRH and galanin immunoreactivities were also detected in the ventral telencephalon. All these neurotransmitters are involved in maintaining the equilibrium of the sleep-wake state. Our results are in accordance with results from rats, further supporting the use of zebrafish as a tool to study molecular mechanisms underlying complex behaviors.

Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity

“…To date, there are four known genes in zebrafish that code for histamine receptors, hrh1 , hrh2a , hrh2b , and hrh3 [177]. In zebrafish, histamine containing neurons have been localized only to the ventrocaudal hypothalamus, though the projections are widespread [137,178]. The distribution of histamine in the zebrafish brain compared to humans is shown in Figure 1E.…”

Interactions of the orexin/hypocretin neurones and the histaminergic system

“…), in rat about 4600 (Ericson et al . ) and in zebrafish 40–45 (Sundvik & Panula ). In these neurones, histamine is packed into vesicles by vesicular monoamine transporter 2 (VMAT2) (Merickel & Edwards ) and not stored in the same vesicles as GABA (Kukko‐Lukjanov & Panula ).…”

“…In the brain of adult zebrafish, neurone numbers can also be quantified. There are no significant differences in the histamine neurone numbers between male and female zebrafish in adulthood, both have 40–45 neurones (Sundvik & Panula ). Both the histaminergic (Eriksson et al .…”

Sites of action of sleep and wake drugs: insights from model organisms

“…Morpholino knockdown of histamine decarboxylase reduces wakefulness [25], as do histamine receptor H1 antagonists, such as pyrilamine, chloropyramine, and loratadine [3**]. Given the molecular and anatomical conservation of the histamine system between fish and mammals, the zebrafish system is a good model for elucidating how histamine H1 antagonists regulate wakefulness [26]. …”