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Caroline H Brennan

CHB is internationally recognized as a leader in the field of zebrafish behavioural analysis and has developed and validated automated assay systems for this purpose. She has a broad background in the use of zebrafish as a developmental and behavioural genetic model system including using zebrafish for behavioural analysis, developmental biology, RNAseq gene expression analysis, and generation and analysis of CRISPR lines [1-3]. Following initial training in adaptive mechanisms underlying drug dependency at KCL CHB's research changed to focus on mechanisms of development, and more recently, cell and developmental mechanisms underlying vulnerability to psychiatric disease. She has more than 20 years’ experience in the use of zebrafish as a model for the study of neuronal patterning, axon path-finding and behaviour. She pioneered the use of zebrafish for addiction-biology research by establishing behavioural assays of nicotine and ethanol-induced reward and dependence in zebrafish [1]. Subsequently, as the result of MRC-UK and internationally funded projects, she expanded her research to include additional assays of psychiatric disease-related endophenotypes (habit formation, impulsivity, novelty preference, behavioural flexibility, social behaviour, number cognition) [4-8]. her group built the first fully automated operant box for adult fish capable of measuring sustained attention and impulse control (5‑choice serial reaction time task)- a version of which was requested by the Science Museum for inclusion in their permanent collection. The first study using this assay identified differences in the levels of trait impulsivity in a strain with a genetic impairment in acetylcholinesterase (AChE) activity [4]. The system has now been refined such that it can be scaled to allow 100s of fish to be assessed each day making the group uniquely placed to carry out large scale behavioural research. CHB has long-standing interaction with industry - she received a Royal Society Industry Fellowship to work with Pfizer Intl. developing assays for their drug safety testing programmes and subsequently acted as consultant for Pfizer. She is a member of the Royal Society's Industry Fellows' College and member of the Royal Society of Biology.

1. Kily LJM, Cowe YM, Cowe, Hussain O, Patel S, McElwaine S, Cotter FE and Brennan CH (2008). Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways. J. Exp Biol 211 (10):1623.

2. **Leggieri,A., García-González, J., Torres-Perez, J.V., Havelange, W., Hosseinian, S., Mech, A.M., Keatinge, M, Busch-Nentwich, E.M and BrennanC.H. Ankk1 loss of function disrupts dopaminergic pathways in zebrafish (2022). Frontiers in Neurosci 16. doi: 10.3389/fnins.2022.794653

3. **Mech, A. M., Merteroglu, M., Sealy, I. M., Teh, M. T., White, R. J., Havelange, W., ... & Busch-Nentwich, E. M. (2022). Behavioral and Gene Regulatory Responses to Developmental Drug Exposures in Zebrafish. Frontiers in Psychiatry, 2383

4. **Parker MO, Brock AJ, Sudwarts A, Brennan CH. (2014) Atomoxetine reduces anticipatory responding in a 5-choice serial reaction time task for adult zebrafish.
 Psychopharmacology (Berl) : 231 (13): 2671-79

5. Parker MO, Evans ADM, Brock AJ, Combe FJ, Teh M-T & Brennan CH (2016) Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood. Addiction Biology 21: 49–60.

6. Parker MO, Garavia, J., Haigh, A., Millington ME; Brown. VJ., Combe. F. J., Brennan. CH. (2012) Discrimination Reversal and Attentional Sets in Zebrafish (Danio rerio). Behav. Brain Res. 232 (1): 264-268.

7. Sheardown, E., Torres-Perez, J.V., Anagianni, S., …and Brennan CH. Characterising ontogeny of numerosity discrimination in zebrafish reveals use of multiple, numerical and non- numerical mechanisms. Proceedings of the Royal Society B, 289 (1968), p.20212544.

8. Torres-Pérez, J. V., Anagianni, S., Mech, A. M., Havelange, W., García-González, J., Fraser, S. E., ... & Brennan, C. H. (2022). baz1b loss-of-function in zebrafish produces phenotypic alterations consistent with the domestication syndrome. iScience, 105704.