The physiological and functional characterisation of the subpallial dopaminergic neurons in larval zebrafish

2020-07-22T09:51:48Z (GMT) by Neal Rimmer
Dopamine is a highly conserved neurotransmitter, and it is known to be involved reward, locomotion, cognition and motivation. Moreover, dysfunction or loss of dopamine neurons has been implicated in diseases such as addiction and Parkinson’s disease, respectively. Dopamine neurons develop early in life, and zebrafish possess a complete compliment of dopaminergic neurons by 5 days post fertilisation. Previous anatomical and genetic studies have suggested the dopaminergic interneurons of the zebrafish subpallium are equivalent to mammalian midbrain DAergic neurons. In this thesis the physiology and functional role of the cluster of dopamine neurons found in the zebrafish subpallium have been examined.
In the first results chapter, the anatomical, morphological and physiological development of subpallial dopaminergic neurons has been examined. This revealed that by 5 dpf, subpallial dopaminergic neurons innervate the telencephalon, thalamus and hypothalamus whilst receiving input from across the brain. Additionally, subpallial dopaminergic neurons receive excitatory and inhibitory synaptic input, are intrinsically excitable and exhibit endogenous firing. Together, these findings suggest the subpallial dopaminergic neurons are functionally integrated into the brain during early development.
In the second and third results chapters, the functional role of subpallial dopaminergic neurons was investigated. To delineate their function, these neurons were targeted for laser ablation. These investigation demonstrated loss of subpallial dopaminergic neurons was sufficient to perturb foraging and startle behaviours in free-swimming fish without affecting locomotion. Physiological recordings revealed these neurons are active when zebrafish are exposed to attractive and aversive stimuli. In sum, these investigations provide insights into the role of dopamine signalling in modulating decision-making, approach, and avoidance behaviours.



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