Multiple types of GABAA responses identified from zebrafish Mauthner cells

Roy, Birbickram; Ali, Declan W.

doi:10.1097/wnr.0000000000000258

Cited by 13 publications

(8 citation statements)

References 17 publications

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“…An alternative cause for the hypersensitivity observed in cyfip2 p400 mutants might be decreased inhibitory input to the M-cell. Larval zebrafish M-cells receive γ-aminobutyric acid (GABA)ergic (Roy and Ali, 2014) and glycinergic inhibitory input from several sources (Koyama et al, 2011; Takahashi et al, 2002), including feedforward neurons (Figure 2A) that have been shown to influence the startle threshold in adult goldfish (Weiss et al, 2008) and African cichlid fish (Neumeister et al, 2010). We therefore measured M-cell glycine receptor (GlyR) expression to assess all glycinergic inhibitory inputs and found no difference in the total intensity of GlyR labeling between cyfip2 p400 mutants and wild-type siblings (Figures S5C and S5D).…”

Section: Resultsmentioning

confidence: 99%

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

et al. 2018

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Sensory experiences dynamically modify whether animals respond to a given stimulus, but it is unclear how innate behavioral thresholds are established. Here, we identify molecular and circuit-level mechanisms underlying the innate threshold of the zebrafish startle response. From a forward genetic screen, we isolated five mutant lines with reduced innate startle thresholds. Using whole-genome sequencing, we identify the causative mutation for one line to be in the fragile X mental retardation protein (FMRP)-interacting protein cyfip2. We show that cyfip2 acts independently of FMRP and that reactivation of cyfip2 restores the baseline threshold after phenotype onset. Finally, we show that cyfip2 regulates the innate startle threshold by reducing neural activity in a small group of excitatory hindbrain interneurons. Thus, we identify a selective set of genes critical to establishing an innate behavioral threshold and uncover a circuit-level role for cyfip2 in this process.

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Section: Resultsmentioning

confidence: 99%

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

et al. 2018

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“…gabra5 transcripts were detected most prominently in the medulla. This staining suggests α5 is expressed in the Mauthner cells, and that α5 containing receptors are likely some of the GABA A isoforms identified via electrophysiology [ 25 ]. gabra6b is expressed prominently in the olfactory bulbs.…”

Section: Resultsmentioning

confidence: 99%

“…In these studies, the GABA A receptor isoforms were not identified. However, patch-clamp recordings of the Mauthner cells showed three distinct GABA A kinetic profiles, which were proposed to be caused by different receptor isoforms [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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“…gabra5 transcripts were detected most prominently in the medulla. The location and expression this subunit suggests it exhibits robust expression in the Mauthner cells, therefore α5 containing receptors are likely some of the GABA A isoforms identified previously via electrophysiology [25]. gabra6b is expressed prominently in the olfactory bulbs.…”

Section: Resultsmentioning

confidence: 90%

Expression of the Eight GABA_A Receptor α Subunits in the Developing Zebrafish Central Nervous System

Monesson-Olson

McClain

Case

et al. 2018

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Multiple types of GABAA responses identified from zebrafish Mauthner cells

Cited by 13 publications

References 17 publications

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

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

Expression of the Eight GABA_A Receptor α Subunits in the Developing Zebrafish Central Nervous System

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Multiple types of GABAA responses identified from zebrafish Mauthner cells

Cited by 13 publications

References 17 publications

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

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

Expression of the Eight GABAA Receptor α Subunits in the Developing Zebrafish Central Nervous System

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Expression of the Eight GABA_A Receptor α Subunits in the Developing Zebrafish Central Nervous System