Distribution and molecular organisation of native kainate receptors in the mammalian central nervous system

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Neurotransmitter receptors are proteins that allow cells in the central nervous system to communicate effectively and rapidly. The vast majority of excitatory neurotransmitter receptors in the mammalian brain are activated by the amino acid glutamate. Glutamate is released from neurons in a highly regulated and activity dependent manner. There are several different classes of receptors which respond to glutamate. The least well characterised of these are the kainate receptors (KARs). It is important to gain more information about the precise distribution, molecular and pharmacological properties of KARs, because increased understanding of the mechanisms that regulate them will allow their involvement in normal brain function to be better defined. In addition, KARs have been implicated in neurological disease states and their activation has been shown to be potently neurotoxic. Recently we have developed a range of new reagents (antibodies) and pharmacological tools which created new opportunities for the selective identification, isolation and analysis of KARs. Our research will exploit the availability of these new tools to provide basic information about the distribution and molecular composition of KARs in different functionally important regions of the adult and developing brain. The development of the brain is a complicated process involving millions of connections forming between neurons. The molecular and cellular mechanisms governing the development of neuronal connections are fundamentally important to normal brain function. Our studies will elucidate the role of KARs in neuronal development. Previous studies established that sensory experience (e.g.: visual experience) guides the development of neuronal circuits. We will test the hypothesis that KARs are influenced by visual experience. The results of the proposed studies may help the future development of therapeutic agents such as anticonvulsants for the treatment of diseases like epilepsy and/or neuroprotective drugs that could be of value for treating conditions such as stroke and head trauma.