KV CHANNELS & MEMORY

The role of the voltage-gated potassium channels and their modulators in mechanisms of plasticity underlying learning and memory in Drosophila

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 Obiettivo del progetto (Objective)

'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.'

Introduzione (Teaser)

Medical trials on fruit flies are revealing how neurons connect and what role this plays in learning. Vital insight into memory and learning is being revealed.

Descrizione progetto (Article)

It is no surprise that researchers, laboratories and psychologists have been trying to understand learning and memory for centuries. The study of learning itself can be probed from many different angles, including at the deep cellular, genetic and biochemical levels.

One way of examining learning and memory is to look at how neurons communicate with each other. The EU-funded 'Kv channels & memory' project is investigating learning in drosophila, also known as the common fruit fly. In cell biology 'Kv channels' stands for voltage-gated potassium channels - mechanisms and areas that play a role in how neurons in the brain fire at each other or communicate. The research team on this project believes that understanding Kv channels will help tease out the mechanisms behind learning and memory.

With this in mind, the team has established a highly multidisciplinary approach involving molecular genetics, biochemistry, cell imaging, electrophysiology and learning trials to take on the challenge.

Because drosophila reproduce and grow quickly, specific mutations can be bred with the desired genetic structure to facilitate testing of certain aspects, such as Kv channels. Specific stocks of drosophila are thus being 'mutated' for each type of Kv channel related to different parts of the insect (antenna lobe, mushroom body, etc). The project is identifying and establishing these in order to examine neuronal and synaptic changes.

These changes are being recorded in parallel with behavioural changes, a process which is identifying specific Kv channels that are implicated in learning and memory.

The research is set to yield important insight into memory and learning in fruit flies, with results that can then be transposed on to humans. This will take researchers a step further in how we learn, with potential for developing treatment regarding learning disabilities, memory loss and more, all thanks to the humble fruit fly.