Murphy Lab ~ Major Projects

• Project 1
• Project 2
• Project 3

Project 1 - Brain circuitry involved in learning and memory

The key way in which the brain works is as a complicated set of circuits, which link up various bits of information, combine them, process them and finally set the body to act.

Some of the primary circuits in the brain which are involved in a particular function, such as those involved in regulating movement, have been reasonably well characterized. However, for the brain functions which underlie higher order behaviours, we have little idea of the brain circuits which are involved.

One of the reasons we know so little is because there have been no good ways of defining these circuits. We have generated transgenic animals, called fos-tau-lacZ mice, which will hopefully allow us to trace the circuits which are used for a brain function. These mice have been designed to express a marker protein in the axons and dendrites of neurons, which have been activated by some functional stimulus. Thus, when the animal is doing something, the neurons, which are involved in that function will "light up", and so will their axonal projections throughout the brain.

Activated neurons in our FTL mice.

FTL projections in the hippocampus - part of the memory system of the brain.

The main research we are doing with these mice is to study how learning and memory work. Hopefully our studies will allow us to determine which brain circuits are used during learning and memory. It will be through the use of these animals that we will be able to test the hypothesis that learning involves changes in the underlying brain circuitry.

Additionally, if we can determine what circuitry is utilised in the learning process, this will help to discover what key brain components are involved in memory, where memory is stored, and how particular memories relate to particular types of behaviours.

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Project 2 - Plasticity in learning and memory.

A spatial maze - to solve this a brain structure called the hippocampus is required.

What we hope to learn in our experiments above is which circuits are involved in the learning of a particular event. But to understand the learning process fully, we need to understand what changes occur in learning which result in the storage of that information in memory. Learning is thought to involve alterations in existing brain circuits. The key is the synapse.

This is the connection between axon and dendrite, and it must be here that any changes in circuitry within the brain must be established. So far, there have been no direct demonstrations of synaptic change underlying a learning process.

We are currently utilizing immunosorbent assays and confocal microscopy techniques to examine changes in the expression of synaptic proteins, in mice, following training on learning paradigms. We are using similar techniques to study the changes, which occur in the brain following exposures to novel environments. These studies are interesting because novel environments have powerful behavioural effects on animals, such as decreasing stress levels and improving their abilities in complex behavioural tasks.

What changes are occuring in this mouse's brain?

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Project 3 - Genetics of Behaviour

        The final area of research involves inherent components of behaviour. There now seems no doubt that variation our behaviour, such as personality type, have a genetic contribution. Depending on the type of behaviour, the genetic component contributes from 40% to 70% of the variation. One such behavioural trait is associated with the way we cope with stressful events in our life.

Our stress response is a natural and important part of our behaviour and contributes to our survival and well-being. However, a prolonged and heightened stress response can have very serious consequences such as long term anxiety states and panic attacks, depression, and susceptibility to cardiovascular disease and immune dysfunction. The way in which individuals respond to stress varies considerably and this variation has a genetic contribution of at about 50%. Clearly, it would be useful to understand which genes are involved in stress response, not only to gain a greater understanding of stress as behaviour, but also to understand how to modify our responses to stress.

We are involved in a study, which will map the genes involved in stress response in an experimental animal model. The final aim of this study is to identify the genes which are involved in the stress response, and how presumed variations in these genes lead to different stress responses and different susceptibilities to the pathological conditions associated with stress.