Excitatory neurons of the cerebral cortex are generated prenatally from a diverse group of neural precursors, some of which have only been identified recently. Radial glia stem cells (RGCs) generate neurons directly and at least three separate lineages of Intermediate Neural Precursor Cells (IPCs), which are themselves produced from RGC, also produce neurons. Intriguingly, neurons within each cortical lamina are derived from these different parent cells. The reason why the neocortex requires so many individual precursor cell types, and whether the diverse ancestry of neurons within each layer plays a functional role in neocortical circuitry, has not been established. The numbers of IPCs are thought to be abnormal in several developmental disabilities, including Fragile X and Down's syndromes. In this project, we identify specific lineages of neocortical pyramidal neurons with novel genetic fate mapping tools and determine their structural, functional and connectional characteristics with patch clamp electrophysiology and high resolution 3D imaging. Our preliminary data indicate that neurons from individual precursor lineages, even within the same lamina, are imparted with specific functional properties and that the multiple IPC groups therefore directly underlie neuron and circuit complexity in the neocortex. Morphological and electrophysiological parameters will be quantitatively examined using a multidisciplinary approach and a two-laboratory collaboration.
The complex circuitry of the brain is formed by neurons which are born from many distinct precursor cells during development, but whether the diverse origins of these neurons leads to functional differences has not been determined. Changes in neural precursor cells have been found in several developmental disorders causing cognitive disability. Thus, understanding how proper circuits are formed will lead to advances in diagnosis and treatment. We have developed molecular techniques which enable simultaneous tracking and functional testing of multiple neuron lineages in vivo. These studies address how circuit complexity is influenced by the diverse population of neural precursor cells.
|Tyler, William A; Medalla, Maria; Guillamon-Vivancos, Teresa et al. (2015) Neural precursor lineages specify distinct neocortical pyramidal neuron types. J Neurosci 35:6142-52|