The present review discusses the functional and molecular diversity of GABAρ receptors. These receptors were originally described in the mammalian retina, and their functional role in the visual pathway has been recently elucidated; however new studies on their distribution in the brain and spinal cord have revealed that they are more spread than originally thought, and thus it will be important to determine their physiological contribution to the GABAergic trans- mission in other areas of the central nervous system. In addition, molecular modeling has revealed peculiar traits of these receptors that have impacted on the interpretations of the latest pharmacolgical and biophysical findings. Finally, sequencing of several vertebrate genomes has permitted a comparative analysis of the organization of the GABAρ genes.

J. Neurochem. (2012)122, 900–910. GABAergic transmission in the neostriatum plays a central role in motor coordination, in which a plethora of GABA‐A receptor subunits combine to modulate neural inhibition. GABAρ receptors were originally described in the mammalian retina. These receptors possess special electrophysiological and pharmacological properties, forming a characteristic class of ionotropic receptors. In previous studies, we suggested that GABAρ receptors are expressed in the neostriatum, and in this report we show that they are indeed present in all the calretinin‐positive interneurons of the neostriatum. In addition, they are located in calbindin‐positive interneurons and projection neurons that express the dopamine D₂receptor. GABAρ receptors were also located in 30% of the glial fibrillary acidic protein‐positive cells, and may therefore also contribute to gliotransmission. Quantitative reverse transcription‐PCR suggested that the mRNAs of this receptor do not express as much as in the retina, and that GABAρ2 is more abundant than GABAρ1. Electrophysiological recordings in brain slices provided evidence of neurons expressing acis‐4‐aminocrotonic acid‐activated, 1,2,5,6‐tetrahydropyridine‐4‐yl methylphosphinic acid‐sensitive ionotropic GABA receptor, indicating the presence of functional GABAρ receptors in the neostriatum. Finally, electron‐microscopy and immunogold located the receptors mainly in perisynaptic as well as in extrasynaptic sites. All these observations reinforce the importance of GABAρ receptors in the neostriatum and contribute to the diversity of inhibitory regulation in this area.

Background: Danio rerio is a powerful experimental model for studies in genetics and development. Recently, CRISPR technology has been applied in this species to mimic various human diseases, including those affecting the nervous system. Zebrafish offer multiple experimental advantages: external embryogenesis, rapid development, transparent embryos, short life cycle, and basic neurobiological processes shared with humans. This animal model, together with the CRISPR system, emerging imaging technologies, and novel behavioral approaches, lay the basis for a prominent future in neuropathology and will undoubtedly accelerate our understanding of brain function and its disorders.Objective: Gather relevant findings from studies that have used CRISPR technologies in zebrafish to explore basic neuronal function and model human diseases.Method: We systematically reviewed the most recent literature about CRISPR technology applications for understanding brain function and neurological disorders in D. rerio. We highlighted the key role of CRISPR in driving forward our understanding of particular topics in neuroscience.Results: We show specific advances in neurobiology when the CRISPR system has been applied in zebrafish and describe how CRISPR is accelerating our understanding of brain organization.Conclusion: Today, CRISPR is the preferred method to modify genomes of practically any living organism. Despite the rapid development of CRISPR technologies to generate disease models in zebrafish, more efforts are needed to efficiently combine different disciplines to find the etiology and treatments for many brain diseases.