2020RAMADHANRAPhD.pdf (4.85 MB)
Role of supraspinal dopaminergic neurons during maturation of zebrafish motor behaviour
thesisposted on 2020-12-03, 12:59 authored by Raad Ramadhan
Dopamine (DA) plays an important role in modulating spinal motor circuits. Studies of both developing and adult zebrafish suggest a role for dopaminergic (DAergic) neurons in regulating spinal motor behaviour, but their role during embryonic maturation of motor output remains unclear. Here, the supraspinal role of DA signalling on early motor behaviour was examined. Firstly, using tyrosine hydroxylase (TH) immunohistochemistry, it was found that TH axons invade the rostral section of the zebrafish spinal cord at around 24 hours post-fertilisation (hpf). Perturbing DA receptor signalling with D4 type DA receptor compounds, knockdown of D4 receptors or ablation of diencephalon DAergic neurons (DDNs) markedly alters the frequency of immature forms of motor behaviour and its corresponding network activity during this developmental stage. In the second chapter, I looked at the effects of DA on immature forms of swimming behaviour of 35 – 48 hpf embryos. Acute application of DA agonists and antagonists did not influence the swimming behaviour at 35 and 48 hpf. However, chronic application of DA agonists and antagonists during development as well as laser ablation of DDNs impacted the duration, velocity, and distance travelled during burst swimming behaviour. In the third chapter, I examined the effects of DA on maturation of synaptic properties and motor network function. Acute applications of DA drugs had no effects on either excitatory or inhibitory miniature post synaptic currents (mEPSCs or mIPSCS) while chronic application modulated spontaneous glutamatergic and glycinergic transmission. DA agonists and antagonists subsequently had no effect on the development of MNs or their branching. Finally, DA agonists, antagonists and DDN ablations had no effect on the synaptic drive underlying burst swimming behaviour at 48 hpf. Taken together, DA signalling might be necessary in regulating early and developing zebrafish behaviour.
Date of award2020-10-19
Author affiliationDepartment of Neuroscience, Psychology and Behaviour
Awarding institutionUniversity of Leicester