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Functional anatomy of a visuomotor transformation in the optic tectum of zebrafish.


Helmbrecht,  Thomas
Department: Genes-Circuits-Behavior / Baier, MPI of Neurobiology, Max Planck Society;

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Helmbrecht, T. (2018). Functional anatomy of a visuomotor transformation in the optic tectum of zebrafish. PhD Thesis, Ludwig-Maximilians-Universität, Graduate School of Systemic Neurosciences (GSN), München.

Cite as: https://hdl.handle.net/21.11116/0000-0003-AFF4-5
Animals detect sensory cues in their environment and process this information in order to carry out adaptive behavioral responses. To generate target - directed movements, the brain transforms structured sensory inputs into coordinated motor com mands. Some of these behaviors, such as escaping from a predator or approaching a prey, need to be fast and reproducible. The optic tectum of vertebrates (named "superior colliculus" in mammals) is the main target of visual information and is known to play a pivotal role in these kinds of visuomotor transformation. In my dissertation, I investigated the neuronal circuits that map visual cues to motor commands, with a focus on the axonal projections that connect the tectum to premotor areas of the tegmentum and hindbrain. To address these questions, I developed and combined several techniques to link functional information and anatomy to behavior. The animal I chose for my studies is the zebrafish larva, which is amenable to transgenesis, optical imaging appr oaches, optogenetics and behavioral recordings in virtual reality arenas. In a first study, I designed, generated and characterized BAC transgenic lines, which allow gene - specific labelling of neurons and intersectional genetics using Cre - mediated recombination. Importantly, I generated a pan - neuronal line that facilitates brain registrations in order to compare different expression patterns (Förster et al., 2017 b ). In a second project , I contributed to the development of an approach that combines t wo - photon holographic optogenetic stimulation with whole brain calcium imaging, behavior tracking and morphological reconstruction. In this study, I designed the protocol to reveal the anatomical identity of optogenetically targeted individual neurons (dal Maschio et al., 2017). In a third project, I took advantage of some of these methods, including whole - brain calcium imaging, optogenetics and brain registrations, to elucidate how the tectum is wired to make behavioral decisions and to steer behavior dire ctionality. The results culminated in a third manuscript (Helmbrecht et al., submitted), which reported four main findings. First, I optogenetically demonstrated a retinotopic organization of the tectal motor map in zebrafish larvae. Second, I generated a tectal "projectome" with cellular resolution, by reconstructing and registering stochastically labeled tectal projection neurons. Third, by employing this anatomical atlas to interpret functional imaging data, I asked whether visual information leaves the tectum via distinct projection neurons. This revealed that two distinct uncrossed tectobulbar pathways (ipsilateral tectobulbar tract, iTB) are involved in either avoidance (medial iTB, iTB - M) or approach (lateral iTB, iTB - L) behavior. Finally, I showed th at the location of a prey - like object, and therefore the direction of orientation swims towards prey, is functionally encoded in iTB - L projection neurons. In summary, I demonstrated in this thesis how refined genetic and optical methods can be used to stu dy neuronal circuits with cellular and subcellular resolution. Importantly, apart from the biological findings on the visuomotor transformation, these newly developed tools can be broadly employed to link brain anatomy to circuit activity and behavior.