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Title: Function and assembly of teneurin-3-positive retinal circuits
Author: Antinucci, Paride
ISNI:       0000 0004 6349 3703
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2017
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The retina is a sensory neural structure formed by multiple classes of excitatory cells (photoreceptors, bipolar and retinal ganglion cells) and inhibitory cells (horizontal and amacrine cells). Its primary role is to detect light stimuli, convert them into electrochemical signals and, subsequently, send the processed information to higher visual nuclei through different types of functionally specialised ganglion cells, the sole output neurons of the retina. Considerable progress has been made in uncovering cellular and molecular mechanisms underlying the assembly and normal functioning of some retinal circuits like, for example, direction-selective circuits. However, little is known about other circuits, such as those generating orientation selectivity in retinal ganglion cells. During my PhD, I started filling this knowledge gap using the larval zebrafish retina as model system. My research focused on circuits composed of neurons that express the transmembrane cell-adhesion protein Teneurin-3. This molecular marker provided a genetic access point to reveal the cellular components and mechanisms of defined retinal circuits. A wide range of techniques, including in vivo confocal and two-photon calcium imaging, BAC transgenesis, TALEN-mediated genome editing, single-cell labelling, pharmacology, optogenetics, as well as a newly generated combinatorial pigmentation mutant zebrafish, were used to dissect a neural circuit underlying the emergence of orientation selectivity in the retina. First, neurons expressing Teneurin-3 in the visual system were characterised. Second, by assessing the role played by Teneurin-3 in the assembly of defined retinal circuits, its requirement in the morphological and functional development of the orientation-selective circuit was revealed. Third, a specific class of orientation-selective amacrine cells with elongated dendritic fields was identified. Notably, these cells generate orientation selectivity in retinal ganglion cells by being a source of tuned GABAergic inhibition. Lastly, evidence showing that orientation selectivity is also present in a fraction of bipolar cell presynaptic terminals is provided. In conclusion, these results define a retinal circuit processing orientation-specific information and identify essential molecular and cellular requirements for its development and function.
Supervisor: Hindges, Robert ; Meyer, Martin Patrick Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available