Grant: Project Grant

The wiring of the brain initially relies on molecular guidance cues that tell cells in one part of the brain where to form connections in other parts of the brain. This is followed by a critical step for fine-tuning of connectivity that relies on specific patterns of activity in brain cells to improve the precision of connections. Because neurons are the only electrically excitable brain cells, the participation of surrounding glial cells in these activity-dependent processes had not been well appreciated until quite recently. This grant proposal aims to use a classic vertebrate brain circuit, the retinotectal system of the Xenopus tadpole, to begin to systematically dissect the signaling between neurons and glia, and the role that these interactions play in circuit refinement during normal development. We will break this problem down into three key questions. The first question is how glial cells detect and respond to activity in sensory inputs. While neuronal responses are well known, the responses of glial cells to stimuli are less well understood. We have novel and unexpected findings explaining how glia in the retinotectal system are able to detect sensory input which we would like to investigate further. In addition once activated it is widely believed that glia release substances called "gliotransmitters" that then act back on neurons. We intend to investigate the nature of these substances and the mechanisms that regulate how they are released. The second outstanding question is how gliotransmitters alter neuronal function and form, modulating intercelluar communication and neuronal growth processes. Finally, we seek to understand the global consequences of glial modulation on the ability of the circuit to process information and to self-organize during development. Thus, this project will expand our understanding of activity-dependent brain circuit development by adding new knowledge of the roles played by these previously under-emphasized glial cells.