Voltage-gated potassium (Kv) channel are neuronal and allow the temporal encoding of information as spike trains in neural circuits. It is therefore important to investigate how each Kv channel is able to do this so that we can better understand how brains work and generate plastic behaviour. In addition genetic diseases (channelopathies) associated with epilepsy, migraine and dementia have been linked to specific mutations in Kv channels. Fundamental research into channels is essential because nearly a third of new therapeutic interventions target channels. Part of the reason for this is the diversity of channel types allowing a large number of targets each with relatively restricted expression and specific control of a particular excitable process. Modulation of Kv channels offers the opportunity to control conditions involving circuit level defects in excitability such as epilepsy, migraine, dementia and depression. Not surprisingly drugs of abuse target channels, therefore this research is hoped to give mechanistic insight into addiction. I wish to determine the role of Kv channels and modulators in mechanisms of plasticity underlying learning in the model system Drosophila. I will address this by genetically removing candidate Kv channels and determining the effect on learning and memory, which is thought to involve modulation of Kv channels. Any behavioural change will be correlated with changes in electrophysiological properties of the appropriate neuronal circuit. Genetic rescue will be used to confirm the role of a given Kv channel in learning and the correlated physiological parameter proposed to be varied by the channel. Changes in neuronal morphology of Kv channel mutant neurons will also be made. Experiments will be performed to determine which signaling molecules modulate Kv channels during learning. These studies may facilitate the future design of therapeutic interventions targeted to specific Kv channel subtypes to alleviate memory deficits.
Project partnersUniversity Of Bristol