Gene-environment interactions and synaptic plasticity in the developing and dysfunctional cerebral cortex

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The cerebral cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form networks underlying our most complex brain functions. It is only after birth, with environmental stimulation, that diverse brain functions begin to emerge. We are interested in the mechanisms whereby the genetic programme regulating maturation of the cerebral cortex is sculpted by interaction with the environment, as well as ongoing gene-environment interactions and mechanisms of plasticity in postnatal brain. Many brain disorders, including schizophrenia, autism, epilepsy, Alzheimer's and Huntington's disease, involve abnormal development or function of the cerebral cortex. Our group has recently demonstrated that onset and progression of Huntington's disease, previously considered the epitome of genetic determinism, can be modulated by environmental factors, suggesting that all brain disorders must involve gene-environment interactions. In this project we are focusing on a specific molecular pathway which processes information from the environment and induces experience-dependent changes in the structure and function of neurons in cerebral cortex. We know that the molecular pathway we are examining has been linked to schizophrenia, a disorder of brain development, and we are attempting to understand how disruption of these molecular pathways can lead to the abnormal brain development and plasticity seen in this disease. We hope to discover neurobiological mechanisms which provide integrative understanding at the level of molecules, networks of neurons, and behaviour, in mouse models of brain disorders with disruption of specific genes, receiving different types of environmental stimulation. Analysing normal mice in this project will also provide new information on mechanisms of plasticity in the healthy cerebral cortex, that may underlie higher brain functions such as learning, which occurs throughout postnatal life, and memory.