Establishing a new, genetically tractable vertebrate brain model with rich behaviour - Danionella translucida
Year: 2021
Type: dissertation
Abstract: Understanding how the brain orchestrates behaviours is a major objective in systems neuroscience. This quest involves accomplishing the following tasks: First, to characterise the behaviour of interest. Second, to identify the neurons and their networks responsible for the behaviour. Third, to study the computations performed by these neurons and fourth, to reveal the underlying mechanisms. As of yet, tackling all of these steps in adult vertebrates has been very challenging due to the size and opacity of their brains. Molecular component of cells, especially lipids and proteins, have light scattering properties and prevent excitation and retrieval of fluorescent signals in deeper brain areas. As a result, only limited optical access can be achieved using microscopy techniques in adult vertebrate brains. In this thesis I introduce a freshwater teleost fish, Danionella translucida (DT), as a new laboratory species. Unlike other vertebrates, it remains small and transparent throughout adulthood, with a majority of its cells accessible to optical recording techniques. Furthermore, DT shows rich social behaviours e.g. sexual behaviour, shoaling, schooling, fighting and, remarkably, vocalisation. This thesis focuses on foundational experiments to establish DT as a new model organism for systems neuroscience. First, I characterise essentials of DT behaviour, in particular its ability to vocalise. Second, I demonstrate genetic tractability to tailor DT for anatomical and functional circuit studies using Tol2-mediated gene insertion of a calcium-sensor and Crispr/Cas9-targeted gene editing for depigmentation. Third, I implement a proof of-principle experiment to show that circuit functionality during sensory stimulation can be tested in the immobilised transgenic animal using two-photon calcium imaging. DT’s optical features combined with rich behaviour and genetic amenability open the way to investigate the underlying mechanisms for neural computations performed by single cells. Hence, establishing DT as a new model organism throughout this thesis enables targeting the fourth and ultimate goal of systems neuroscience in the adult vertebrate.
Author: Schulze, Lisanne
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6944040631