Integrated nanoscopy and microscopy in 3-D to study hippocampal neurogenesis at the synaptic and molecular level.

This research proposal aims to analyse the role of a feeding-associated hormone in stimulating the generation of new brain cells. The ability to generate new adult brain cells is very important for normal healthy brain function. A reduced ability to form new neurones is associated with the common and debilitating brain disorders, dementia and depression.
This research will use state-of-the-art tools, established by engineers, that will allow us to look at brain cells in far greater detail than previously possible. The application of these nano-scale tools to neuroscience will provide invaluable information on the precise structure and function of brain cells over time. Ultimately, this novel approach will characterise the mechanism of new brain cell generation leading to new targets for the treatment of dementia and depression.

The birth of new neurones (neurogenesis) in the adult mammalian brain is an important process involved in protecting against the age-related decline in cognitive function and protects against certain neurodevelopmental disorders. Aberrant neurogenesis, particularly in the brain?s learning and memory centre (hippocampus) is linked to cognitive decline (dementia), as well as behavioural deficits (depression) in adults. Whilst advances have been made in our understanding of neurogenesis, we have yet to determine the complex molecular and neuronal mechanisms that underpin this process and its relationship to neuronal disorders. Furthermore, current imaging techniques allow relatively low optical-resolution at the micrometer level, telling us little about the morphological adaptations that occur during neurogenesis. To address this issue we intend to use state-of-the-art nanoengineering tools (i.e combined Confocal/Atomic Force Microscope with associated transmission scanning electron microscopy) to test the hypothesis that the gut and brain peptide ghrelin protects against dementia and depression via the promotion of hippocampal neurogenesis. This research would lead to the development of nanoscale methods for assessing neuronal function at the synaptic and molecular level, whilst also establishing a legacy of interdisciplinary research between the physical and life science sectors.