Grant: Operating Grant

There are two main types of cells in the central nervous system, glial cells and neurons. Until recently, glial cells were primarily considered to play a supportive role, maintaining a stable environment and supplying nutrients and essential metabolites for the neurons, which were considered to be solely responsible for the integrative, information processing functions of the brain. However, we are now learning that glial cells, which greatly outnumber neurons, can receive and send chemical signals called gliotransmitters to other glia cells and neurons and are actively involved in determining how information is processed. ATP features prominently in glial signaling. A significant challenge facing efforts to understand the functional significance of glia for neuronal networks in health and disease is the difficulty of selectively manipulating and measuring the activity of neuronal vs glial cell populations. The aim of this proposal is to understand the respective roles of neurons and glia, and the transmitter ATP, in producing adaptive breathing responses to periods of low oxygen (hypoxia), which are common in many types of sleep-disordered breathing, and potentially life threatening in premature and newborn infants.We will apply high resolution electrophysiological, pharmacological and imaging methodologies to discretely monitor the responses of neurons and glia to specific stimuli in a region of the brain critical for generating breathing. Importantly, we will also employ novel optogenetic approaches (which combine genetic engineering with light to control specific groups of cells) to selectively activate glial cells to understand how these previously neglected cells contribute to such basic homeostatic processes. These studies will provide invaluable insight into the role of ATP signaling, neurons and glia in modulating respiratory network activity, and how these different elements might be manipulated to stimulate breathing during periods of low oxygen.