Collaborative Research: The Role of Extracellular H+ in Processing Visual Signals

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

Proper signaling by neurons in the central nervous system is essential in enabling organisms to perceive the world around them and to respond appropriately and adeptly to challenges in their environment. Glial cells (support cells that wrap and envelop nerve cells and are at least as numerous as the neurons themselves) are known to modulate neuronal signaling, but the molecular mechanism(s) by which they exert their effects is largely unknown. This work will test the hypothesis that glial cells modify neuronal signaling by altering levels of extracellular acidity, decreasing neurotransmitter release from neurons. The research program will be conducted in the context of a unique research and teaching collaboration in which undergraduates and faculty from a primarily undergraduate institution are active participants in testing important fundamental questions in neurobiology in conjunction with students and faculty at several research-intensive universities. Using the vertebrate retina as a model system, the study will employ ultra-sensitive self-referencing H+-selective microelectrodes in conjunction with newly developed H+-imaging technologies to measure levels of extracellular H+ from isolated cells and within the intact retina. The ionic and molecular mechanisms that mediate glial cell-induced extracellular acidifications will be examined. Electrophysiological methods will be used to monitor how glial cell activation alters the flow of neuronal information processing in retinal slices. The research will help to resolve a current controversy regarding the potential role that changes in extracellular acidity play in retinal function. These findings also have the potential to answer a long-standing mystery of retinal function - why tonic depolarization of photoreceptors, which occurs in darkness, does not lead to excess release of neurotransmitter and consequent death of neurons by glutamate-induced excitotoxicity. The results of these studies are likely to have broad implications for neuroscience generally: glial modulation of neurotransmitter release via increases in extracellular H+ may be a widely used mechanism to regulate synaptic strength and prevent glutamate-induced excitotoxicity throughout the nervous system.