Expression of the eight GABAA receptor α subunits in the developing zebrafish central nervous system

Abstract

GABA is a robust regulator of both developing and mature neural networks. It exerts many of its effects through GABAA receptors, which are heteropentamers assembled from a large array of subunits encoded by distinct genes. In mammals, there are 19 different GABAA subunit types, which are divided into the α, β, γ, δ, ε, π, θ and ρ subfamilies. The immense diversity of GABAA receptors is not fully understood. However, it is known that specific isoforms, with their distinct biophysical properties and expression profiles, tune responses to GABA. Although larval zebrafish are well-established as a model system for neural circuit analysis, little is known about GABAA receptors diversity and expression in this system. Here, using database analysis, we show that the zebrafish genome contains at least 23 subunits. All but the mammalian θ and ε subunits have at least one zebrafish ortholog, while five mammalian GABAA receptor subunits have two zebrafish orthologs. Zebrafish contain one subunit, β4, which does not have a clear mammalian ortholog. Similar to mammalian GABAA receptors, the zebrafish α subfamily is the largest and most diverse of the subfamilies. In zebrafish there are eight α subunits, and RNA in situ hybridization across early zebrafish development revealed that they demonstrate distinct patterns of expression in the brain, spinal cord, and retina. Some subunits were very broadly distributed, whereas others were restricted to small populations of cells. Subunit-specific expression patterns in zebrafish resembled were those found in frogs and rodents, which suggests that the roles of different GABAA receptor isoforms are largely conserved among vertebrates. This study provides a platform to examine isoform specific roles of GABAA receptors within zebrafish neural circuits and it highlights the potential of this system to better understand the remarkable heterogeneity of GABAA receptors.

Abnormal expression of GABAAreceptor sub-units and hypomotility upon loss ofgabra1in zebrafish

“…Over the course of development the expression of gabra1 became more restricted to the midbrain-hindbrain regions (Fig. 2) consistent with previously published work (Monesson-Olson et al, 2018; Samarut et al, 2018).…”

Abnormal expression of GABAA receptor sub-units and hypomotility upon loss of gabra1 in zebrafish

“…Over the course of development the expression of gabra1 became more restricted to the midbrainhindbrain regions (Fig. 2), consistent with previously published work (Monesson-Olson et al, 2018;Samarut et al, 2018).…”

Differential effects of ethanol on behavior and GABAA receptor expression in adult zebrafish (Danio rerio) with alternative stress coping styles

“…Published data suggest that within broad brain divisions implicated in regulating stress (e.g. telencephalon, diencephalon), α 1 -, α 2 -, and γ 2 -subunits of GABA A R showed similar expression across individuals in the telencephalon and olfactory bulbs, but were more variable within the diencephalon 84 – 86 . While studies have demonstrated differences in GABAergic neurons and GABA A R neurons across broad divisions of the zebrafish brain 84 – 86 , to our knowledge no study has mapped and quantified GABA A R distribution at the resolution of individual brain nuclei in zebrafish.…”