Final Report Summary - YOUNG MINDS (The synaptic development of cortical circuitry in the young brain) This Marie Curie Career Integration Grant was awarded to facilitate the establishment of the new research group of Dr Michael Ashby at the University of Bristol, UK and to promote my successful integration to the European research community as I moved back from the USA. The overarching research question for my laboratory is “how is the brain formed when we are very young and how does our environment influence this development?” To achieve this, we use high resolution optical stimulation and recording combined with molecular, genetic and electrophysiological methods. Ultimately, we aim to define how neonatal sensory experience influences the normal and pathological cortical circuit development that underlies lifelong brain function.Having established laboratory space and configuration of appropriate equipment, the experimental models that underpin our research were set up. In the initial period, these models were to be used in specific projects aimed at: (1) understanding the growth of the very earliest neuronal networks in the sensory areas of the brain; (2) to measure the effects of premature birth and early sensory exposure on subsequent brain development. More recent developments have seen the research group diversify to applying our expertise in synaptic and circuit function to the pathology of dementia. Excellent postdoctoral researchers and postgraduate students have been recruited and trained. Two postgraduate students have now graduated and one postdoctoral researcher has just gained a new position at a major Australian University. Another postdoctoral researcher has recently gained fellowship funding to continue their work in the group.Our new findings include the discovery of previously-unknown changes in the connections between neurons in the developing sensory cortex. This finding is potentially leading us towards a novel description of how the cortex is initially formed and therefore how sensory experience can alter it as it grows. Also, we have established and characterised a rodent model of premature birth. In parallel, through a new collaboration with clinician colleagues, we have established structural and functional measurements of brain development in prematurely-born children. We are now in the process of linking these clinical findings to the rodent model, so that future research in that pre-clinical model will be directed towards the most appropriate stage of development in children. Our aim is to identify novel biomarkers of brain development following premature birth based on our understating of the functional development of cortex in our pre-clinical experiments. Such biomarkers could then be used to assess the trajectory of brain development in vulnerable infants. Our work on dementia has shown that synaptic dynamics are altered much earlier in the disease than previously thought, raising the possibility of an early therapeutic intervention targeted to synapse function.
