Zebrafish Serotinergic System

Serotonergic schematic

A simple schematic representing a lateral view of the larval zebrafish brain at around 3dpf (anterior to the left). The approximate locations of serotonergic nuclei. The principle regions of 5HT expression are the raphe, the periventricular region of the caudal hypothalamus (Hc) the posterior tegmentum (PT), the pretectum (Pretect) and the pineal (Pin). Tect = tectum, Tel = telencephalon, OB = olfactory bulb and AC is anterior commissure Based on Lillesaar 2011

The serotonergic system describes the system of neurons in the brain that employ serotonin (5-hydroxytryptamine;5HT) as a neurotransmitter.  The system has been fairly well characterised in the adult (see Lillesaar review ), there have also been many efforts to characterise the system in the embryo and larva.  The system is a current focus of multiple laboratories because of its clinical importance in several psychiatric (eg affective disorders) and neurological (eg migraine) pathologies.

Anatomically there are four main groups of serotonergic neurons in the brain: 1. the pretectal population, the hypothalamic and posterior tuberculum populations and the raphe populations, there are also 5HT-positive neurons in the epiphysis and area postrema.

Serotonin belongs to the tryptamine class of neurotransmitters as they are synthesised from tryptophan.  The tryptamines in turn are part of the monoaminergic class of neurotransmitters which additionally includes the catecholamines (including dopamine, synthesised from tyrosine), Histamine and other amines.

Transgenics and molecular markers

Antibodies raised against 5HT can be used in immunohistochemical interrogation of zebrafish brain preparations, examples are shown in images associated with this tutorial.  In addition to this, the Tg(pet1:GFP)(Lillesaar et al., 2012), Tg(pet1:KALTA4) and Tg(VMAT:GFP) transgenic line marks some of the populations of serotonergic neurons.

Antibodies that label serotinergic neurons

Transgenic lines that label serotinergic neurons

Key Publications

The serotonergic system in fish.
J Chem Neuroanat (2011) vol. 41 (4) pp. 294-308

Gaspar & Lillesaar.
Probing the diversity of serotonin neurons.
Philos Trans R Soc Lond B Biol Sci. 2012 Sep 5;367(1601):2382-94. doi: 10.1098/rstb.2011.0378.

Lillesaar et al.
Axonal projections originating from raphe serotonergic neurons in the developing and adult zebrafish, Danio rerio, using transgenics to visualize raphe-specific pet1 expression.
J Comp Neurol. 2009 Jan 10;512(2):158-82. doi: 10.1002/cne.21887.

Panula et al.
Modulatory neurotransmitter systems and behavior: towards zebrafish models of neurodegenerative diseases.
Zebrafish (2006) vol. 3 (2) pp. 235-47

McLean and Fetcho.
Ontogeny and innervation patterns of dopaminergic, noradrenergic, and serotonergic neurons in larval zebrafish.
J. Comp. Neurol. (2004) vol. 480 (1) pp. 38-56

Wen et al.
Visualization of monoaminergic neurons and neurotoxicity of MPTP in live transgenic zebrafish. Developmental Biology (2008) vol. 314 (1) pp. 84-92