Rho-family GTPases in Synaptic Plasticity

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The research proposed in this application involves the molecular mechanisms of memory formation and basic brain function. Nerve cells (neurons) in the brain communicate with one another at connections called synapses, by releasing a chemical (neurotransmitter) that travels across the synapse and activates a receptor in the adjacent neuron. Synapses can change their strength by changing the number of neurotransmitter receptors in the synapse by trafficking the receptors to and from the synapse. Furthermore, the structure of the part of the cell close to the synapse (called the dendritic spine) can change by rearrangements of the cell skeleton (the cytoskeleton). These events occur in processes known as synaptic plasticity, which are thought to represent a molecular/ cellular correlate of learning and formation of memories. In this study, we aim to further the understanding of the molecular changes that occur in synaptic plasticity. We have found that a protein pivotal for neurotransmitter receptor trafficking in synaptic plasticity physically interacts with two other proteins that are known to function as molecular switches for a wide range of cellular processes that are controlled by a variety of cell signals. We will investigate why these molecular switches interact with the trafficking protein. We propose that they respond to the cell signals that induce synaptic plasticity in the brain and influence the trafficking of neurotransmitter receptors to bring about changes in synaptic strength. Furthermore, these novel interactions may provide a means for coupling trafficking and cytoskeletal changes during synaptic plasticity. This work is important because it will lead to a wealth of novel information about the molecular mechanisms of learning and memory, which malfunction in disorders such as Alzheimer s disease. The public is able to access the progress of neuroscience research in the University of Bristol via Bristol Neuroscience (BN). BN is a recently-formed organisation that brings together all aspects of neuroscience, specifically with the aim of advancing understanding of the basic principles of the nervous system and development of new treatments for neurological disorders and disease. There is an extensive website that allows the public to gain access to the research going on in our labs. BN is also active in arranging various activities such as talks at local schools and events to increase public understanding of science.