Serotonin is a key modulator of locomotor activity in the brain and spinal cord of vertebrates. A wide range pharmacological and lesion studies have provided important information about the role of serotonergic systems in modulation of motor output. However, the specific behavioural contexts under which serotonin is released remain poorly understood. This is primarily because mammalian models are not accessible to detailed in vivo study. As such, the relationship between serotonergic interneuron activity and different forms of behaviour remains largely unexplored. In order to address this issue, you will use larval zebrafish examine the dynamics of serotonergic neuron in an awake, intact animal. Zebrafish larvae are an excellent model for such studies as serotonergic systems form during early stages of life at a time when these animals are readily accessible to both in vivo imaging and electrophysiological approaches.
In this project, you will use patch clamp electrophysiology and calcium imaging approaches to study the activation patterns of serotonergic interneurons in the brainstem and spinal cord of awake zebrafish larvae as they undergo various forms of motor activity. This will allow us to determine the behavioural contexts leading to activation of these interneuron populations. Subsequently, you will use targeted ablation methods to remove populations of serotonergic interneuron from the larval brain and study the behavioural consequences as fish navigate a virtual reality environment. Finally, you will use in vivo imaging methods to label serotonergic interneurons and track connectivity with different neuronal populations and study the effects of serotonin on the physiological properties of neurons with which they synapse.
Techniques that will be undertaken during the project
-In vivo electrophysiology -Calcium imaging -Voltage-clamp -Immunohistochemistry -Genetics