Endogenous dopamine suppresses initiation of swimming in pre-feeding zebrafish larvae

Dopamine is a key neuromodulator of locomotory circuits, yet, the role that dopamine plays during development of these circuits is less well understood. Here, we describe a suppressive effect of dopamine on swim circuits in larval zebrafish. Zebrafish larvae exhibit marked changes in swimming behavior between 3 days post fertilization (dpf) and 5dpf. We found that swim episodes were fewer and of longer durations at 3dpf than at 5dpf. At 3dpf, application of dopamine as well as bupropion, a dopamine reuptake blocker, abolished spontaneous fictive swim episodes. Blocking D2 receptors increased frequency of occurrence of episodes and activation of adenylyl cyclase, a downstream target inhibited by D2-receptor signaling, blocked the inhibitory effect of dopamine. Dopamine had no effect on motor neuron firing properties, input impedance, resting membrane potential or the amplitude of spike after-hyperpolarization. Application of dopamine either to the isolated spinal cord or locally within the cord does not decrease episode frequency, whereas dopamine application to the brain silences episodes suggesting a supraspinal locus of dopaminergic action. Treating larvae with 10{micro}M 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine hydrochloride (MPTP) reduced catecholaminergic innervation in the brain and increased episode frequency. These data indicate that dopamine inhibits the initiation of fictive swimming episodes at 3dpf. We found that at 5dpf, exogenously applied dopamine inhibits swim episodes yet the dopamine reuptake blocker or the D2 receptor antagonist have no effect on episode frequency. These results lead us to propose that endogenous dopamine release transiently suppresses swim circuits in developing zebrafish