DOES TBI ALTER EXTRINSIC AND INTRINSIC CONNECTIVITY IN SENSORY CORTEX?

Our overall hypothesis states that a simple CNS circuit can be repaired after TBI using neural progenitor cells. We use the barrel cortex as our primary model of a cortical circuit. The barrel cortex is a region in the rodent CNS that contains a distinct representation of the whiskers. Each whisker is represented by a discrete anatomical structure in the neocortex called a barrel. The cellular structure of a barrel differs slightly from species to species, but basically consists of a ring of cells in layer 4 in the neocortex that connects structurally and functionally to the layers above and below. Each layer within a barrel column has distinct cell types and functions. The task of this proposal will be to reconstruct as closely as possible the distribution of cell types in a brain injured slice in the barrel cortex. Because this region contains a confined iterative architecture it should be possible to reconstruct a circuit responsive to stimulation. Similar possibilities also relate to the olfactory bulb, which contains a simple circuit composed of several well characterized cell types: principal cells receiving afferents from olfactory sensory neurons and interneurons. In addition, cells populating the olfactory bulb are generated throughout life and therefore provide a potential supply of newly differentiated progenitor cells to use for circuit reconstruction after TBI.