Molecular and structural determinants of plasticity in the cerebral cortex

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The cerebral cortex is most highly developed in man. It gives us important abilities and attributes such as the ability to see, feel and hear the world around us and to remember and recognise these features. The cortex is also responsible for higher order cognitive abilities such as speech, planning, abstraction and imagination. One of the key properties of the neurons in the cerebral cortex is their ability to change their connections with one another in responses to lasting changes in the environment or in response to injury. This process is known as synaptic plasticity; ?synaptic? because synapses form the connections between neurons and ?plasticity? because once changed, the synapses stay in their new form until made to change again. Without synaptic plasticity the brain is unable to develop properly. Synaptic plasticity disorders can lead to mental retardation during development. Synaptic plasticity is also required for normal memory formation and is impaired in Alzheimer?s disease. During recovery from stroke, synaptic plasticity is required in order to reassign function among the cells that survive the injury. It is beneficial for us to understand the basic mechanisms of synaptic plasticity in order to envisage therapies for enhancing recovery from stroke, for increasing the ability to learn in mental retardation and increasing the ability to remember in Alzheimer?s disease. This set of studies aims to advance our understanding of synaptic plasticity by finding out the links between the early stages of plasticity that are at present reasonably well understood and the structural changes in plasticity that ensue that are not at all well understood. We will do this in a relatively simple area of cortex concerned with processing information from the tactile surface of the body known as the somatosensory cortex. We will directly observe physical changes in the connections between neurones using a specialised microscopy method that allows repeated viewing of the same neurons over days and weeks. We will use genetic mutations to understand the molecules controlling these physical changes. We will study the effect of sensory experience on the connections in the cortex, which is of direct relevance to physiotherapy used during rehabilitation from stroke. Results from these studies should ultimately provide us with methods for improving recovery from stroke and potential therapies for learning and memory disorders.