Identification of NMDA receptor subunits contributing to midbrain dopaminergic learning and behavioural functions

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Many nerve cells in the brain communicate with each other by releasing chemicals known as neurotransmitters. Nerve cells depend on these chemical signals in order to carry out the functions of the brain, and any errors in neurotransmitter signalling can give rise to brain diseases, such as Parkinson's disease or drug addiction. One important neurochemical in the brain is the amino acid, glutamate. Glutamate is released from many nerve cells, and stimulates target cells by binding to receptor proteins specialised to recognise glutamate. Among the family of glutamate receptor proteins, one in particular is very interesting because it can have both beneficial effects and harmful effects on the brain. This receptor protein, known as the 'NMDA receptor', is required for the normal development of the brain from childhood to adulthood, and is also activated while the brain is learning and acquiring new information and memories. However, this receptor can be active under conditions that cause cells to die- this is known as neurodegeneration. Scientists have been interested in NMDA receptors for many years, and NMDA receptors have been identified and carefully characterised in several brain regions. However, one brain region where little is known about NMDA receptors is a set of nerve cells that are though to be important in controlling our movements, and in making us feel rewarded and motivated. These nerve cells release another important brain chemical known as dopamine. They are believed to be affected in several brain diseases, including Parkinson's disease, schizophrenia and drug addiction. NMDA receptors are believed to have an important role in controlling the behaviour of dopamine nerve cells, but at present, we do not know which kinds of NMDA receptors are found here, or what beneficial or harmful effects NMDA receptors have on these cells. This project aims to characterise NMDA receptors in dopamine nerve cells, and to link the activity of NMDA receptors to a simple behavioural learning process. Not only will the results from this project provide new information about how NMDA receptors are involved in the normal function of dopamine nerve cells, but it might reveal new NMDA receptor targets for developing therapies in some of the brain diseases mentioned.