Characterising the role of the locus coeruleus norepinephrine system in the zebrafish model — The Association Specialists

Characterising the role of the locus coeruleus norepinephrine system in the zebrafish model (21517)

Rebecca Lee 1 , Marcello Lepre 1 2 , Cheryl Lee 2 , Elizabeth O'Brien 1 , Raphael Ricci 2 , Carlie Cullen 2 , Itia Favre-Bulle 1 3
  1. Queensland Brain Institute, Brisbane, Queensland, Australia
  2. Mater Research Institute-UQ, Brisbane, Queensland, Australia
  3. School of Mathematics and Physics, The University of Queensland, Brisbane, Queensland, Australia

 

The locus coeruleus (LC) is an anatomically small, yet functionally powerful nuclei that is the main source of norepinephrine (NE) to the central nervous system and is essential for several key cognitive processes. Despite its small size, current understanding of the circuitry underlying the LC-NE system remains limited due to its positioning within the brainstem. In the zebrafish, the LC is evolutionarily conserved and composed of approximately 10 neurons. This low number of neurons alongside the advantage of optical transparency in zebrafish offers the opportunity to comprehensively characterise the LC-NE system. In this study, we have established a series of transgenic zebrafish lines that target the LC-NE system using genetically encoded calcium indicators and opsins. Previous work has established that dopamine beta hydroxylase (DBH) selectively labels NE neurons. Therefore, using the strengths of the Gal4/UAS system, we established transgenic lines through the injection of dbh:Gal4. Collectively, these transgenic lines characterise the LC-NE system in terms of its structural, functional, and circuitry implications. Preliminary work using these zebrafish lines have seen heterogeneity in the number of LC-NE neurons both between fish and within each fish bilaterally. Additionally, the calcium activity of LC-NE neurons also appears to show differing response profiles across individual cells. This provides supporting evidence for the emergent theory that LC neurons act independently to achieve specific cognitive goals. Through manipulation of the LC-NE system with sensory stimulation and optogenetics, this study will provide key insight into the level of influence the LC has on sensory processing.