DOPAMINERGIC NEUROMODULATION OF TONICALLY FIRING PURKINJE NEURONS IN LARVAL ZEBRAFISH

The brain is composed of intricate neural networks which need to be altered to generate varied behaviours. Reconfiguration of these circuits by neuromodulators can change neuronal output by affecting their intrinsic properties or the synaptic efficacy of the circuit. The larval zebrafish shows catecholaminergic projections into the cerebellum, prompting us to investigate their role in modulating Purkinje neuron (PN) activity. PNs display one of two firing patterns: tonically firing when depolarized and burst-like activity when hyperpolarized. We pharmacologically modulated dopaminergic receptor activity by superfusing antagonists in live, paralyzed larval zebrafish and recorded electrical activity of PNs using loose patch recordings. We observed that blocking dopamine receptors (both D1-like and D2-like) induced a switch from spontaneously tonic PNs to a burst-like pattern with a decrease in simple spike frequency. When synaptic inputs to PNs are blocked, this change in state is abolished indicating its dependency on external inputs and only a decrease in simple spike frequency was observed. Spontaneously bursting PNs do not show any change in state when dopamine receptors are blocked but show a decrease in the frequency of simple spikes. These suggest a two-fold effect of dopamine on the cerebellar circuitry: both at the network level switching tonically firing PNs to a burst like state as well as intrinsic effect at the cellular level of the PN.