Neuronal identity is established during development through a complex set of events that combine both genetic and activity dependent mechanisms. Interneurons within the forebrain provide a particularly attractive context to explore the process by which cell identity is achieved, as populations derived from focal sources disperse across a variety of pallial and subpallial circuits. In this proposal, we develop and combine multi-disciplinary methods that allow a precise assignment of lineage boundaries within groups of interneurons to determine the significance of clonality for cell migration and the integration of sibling cells into a wide swath of diverse circuits. Moreover, by combining a fine grain lineal analysis with RNA-Seq methodologies, coupled with physiological measures, this proposal will provide unprecedented insight into how developmental events and changes in gene expression manifest the establishment of both complex and diversity excitatory (Cortical, Hippocampal and lateral Amygdala) and inhibitory (Striatal and medial Amydala) circuits. This will be achieved through the execution of three independent but interrelated aims.
Aim 1 will provide a comprehensive determination of interneuronal lineage and subtypes.
Aim2 will complement this by providing a ?ground truth? understanding of how gene expression evolves in sister interneurons derived from a common clone. Finally aim 3 will provide insight as to how activity regulates gene expression in establishing the connectivity and intrinsic physiology of different interneuron subtypes. The successful execution of these aims will fundamentally allow use to understand the interplay between pre-existing intrinsic programs against extrinsic signals in the development of forebrain interneuron diversity.
Our aim by the completion of the funding for this proposal is to establish how interneuron progenitors within the forebrain develop to maturity regarding their lineage relationships relative to their emergent molecular and physiological properties.
Showing the most recent 10 out of 38 publications
