The research in our laboratory focuses on developmental and activity dependent changes in the molecular organisation and function of glutamate and GABA receptors in the central nervous system. These receptors are thought to be involved in events such as synapse formation, learning and memory, as well as neuronal plasticity and disease processes.

Molecular mechanisms of neuronal plasticity

The amino acid glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS), and it exerts its physiological effects by binding to a number of different ionotropic (ligand-gated ion channels; Figure 1) and metabotropic (G-protein-coupled) glutamate receptors. In addition to excitatory neurotransmission, glutamate receptors play an essential role in neuronal differentiation, plastic changes in efficacy of synaptic transmission, neurodegeneration, and neuronal cell death.

The research in our laboratory focuses on developmental and activity dependent changes in the molecular organisation and function of glutamate receptors in the CNS. We are particularly interested in the molecular mechanisms underlying the expression, regulation and subcellular targeting of glutamate receptors and modulation of synaptic efficacy. We study the mechanism of ionotropic glutamate receptor subunit assembly, synaptic expression and the role of receptor-associated proteins. A major focus of our research is on the role of different ionotropic and metabotropic glutamate receptors in long-term activity-dependent changes in the strength of synaptic transmission.

We use a combination of biochemical, immunocytochemical, fluorescence imaging, pharmacological-, molecular- and cell biological approaches. Our studies allow us to gain some understanding of the rules neurons follow during the expression, assembly and cell surface targeting of glutamate receptors, and the mechanism by which synaptic input controls a neuron's ability to modify its synapses.

Oligodendrocyte development, survival and vulnerability in the immature brain

Oligodendroglial cells are located in the area of the brain called 'white matter' where they provide support to nerve cells. Normal development of oligodendrocytes and myelin formation are complex procedures, regulated by a wide range of cellular interactions. Oligodendrocytes respond to various chemical signals in the developing brain and they alter their proliferation, migration, differentiation and myelin formation. Immature oligodendroglial cells are very vulnerable in the developing brain and they are often damaged if they are poorly supplied with oxygen (eg poor lung function or birth complications). The selective death of oligodendroglial cells can severely disrupt myelination in newborn infants, which can lead to major neurological complications later in life. Memory and movement disorders frequently develop following extensive lesions of the immature oligodendroglial cells in brain white matter.

Recently we have identified receptors, which mediate the actions of the major brain transmitter chemicals glutamate and GABA in immature oligodendroglial cells (Figure 2). Glutamate and GABA are released from active nerve cells and they represent chemical signals for cells in the brain including the oligodendrocytes. The activity dependent release of glutamate and GABA from nerve cells may influence oligodendrocyte development and survival in the brain. We currently investigate the role of these receptors in oligodendroglial development, myelin formation, survival and regeneration following white matter damage. Better understanding of these basic cellular and molecular events in the premature brain is essential for the development of effective treatment strategies for white matter damage.