Abstract
The brain's ability to process information and guide behaviour is reliant on diverse neurons forming complex neuronal circuits. In this PhD project proposal, we set out to explore how such diversity in neurons and synaptic circuits arises with a focus on embryonic progenitor origin and using mouse as a model organism. Recently data from my lab and others suggest that key aspects of neuronal identity and synaptic specificity in both cortex and striatum are controlled by their embryonic progenitor origin. In this proposal we will explore this further and focus on the striatum, but the tools and approaches generated will be universally applicable. The PhD project proposal has four main Objectives. Firstly, we will use RNA sequencing approaches to genetically parse the different embryonic progenitors that generate striatal spiny projection neurons (SPNs) and generate tools for their fate mapping from embryo to adulthood. Secondly, we will use a variety of techniques on adult SPNs to determine what 'types' of neurons arise from different progenitor pools. Thirdly, we will use novel viral tracing approaches to observe the synaptic integration of striatal SPNs within larger brain circuits. Lastly, we will reveal the molecular recognition systems that different embryonic progenitor-derived SPNs employ to achieve synapse specificity within these larger circuits. Together they will provide new insights how the vast complexity of neurons and circuits in the striatum arises and open avenues for future study of the roles for embryonic progenitor origin in neurological and neurodevelopmental disorders.
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