Research in our laboratory investigates the genes and neural circuits that control aggression, an adaptive behaviour that animals use to establish social hierarchies and fight for resources such as food or territory. We have recently shown that the potent and selective Phosphodiesterase 5 inhibitor sildenafil reduces zebrafish aggression, likely by activating Purkinje cells in the cerebellum. Acute inhibition of Pde5 decreases aggression levels without affecting locomotion or anxiety. This observation provide us with an opportunity to characterise one of the neural circuits that controls the aggressive response to visual stimuli in the zebrafish brain.
In this project we will develop state of the art genetic tools to manipulate Purkinje cell activity and measure neural activity (by electrophysiology) and behaviour. We will first examine sildenafil activity on Purkinje cell firing by patch clamp. We will then use an enhancer for the carbonic anhydrase 8 gene to drive Channelrhopdsin or TRP channel expression in Purkinje cells. Electrophysiology recording will permit neural activity driven by ChR2 to be compared to sildenafil application. In a second step, we will record the aggressive interaction of a fish with its own mirror image with and without optogenetic or chemogenetic stimulation, hypothesising that activation of Purkinje cells should decrease zebrafish aggression. These results will be contrasted to the expression of other behaviours upon cerebellar activation, giving an idea about the selectivity of Purkinje cell function.
In the second part of this project we will further characterise components of this neural circuit in relation to aggression, including the eminentia thalami, habenula and raphe nucleus. This will include tracing the afferent and efferent connections between areas and identifying further markers for subcomponents of this circuit.