Kathleen R. Zahs, Ph.D. Associate Professor of Physiology

Work in the laboratory is aimed at better understanding the functions of glial cells in the central nervous system. We are especially interested in intercellular signaling between glia and between glia and neighboring neurons. We use the mammalian retina as a model system, because retinal glial cells (astroctyes and Müller cells, specialized radial glial cells of the retina) are easily identifiable and accessible for electrophysiological recording and imaging studies.

In collaboration with Dr. Eric Newman, we have demonstrated intercellular Ca2+ waves (increases in intracellular Ca2+ concentration that are propagated to cells distant from the site of local stimulation) in astrocytes and Müller cells of the acutely isolated rat retina. There has been speculation that Ca2+ waves in astrocytes might constitute an extraneuronal signaling pathway in the brain, and we are exploring the functional consequences of intercellular calcium waves in glial cells. A major finding is that glial Ca2+ waves are correlated with changes in the light-evoked activity of neighboring retinal neurons. In collaboration with Dr. Robert Miller, we have shown that retinal glial cells contain D-serine, a co-agonist at the NMDA type of glutamate receptor, and its synthetic enzyme, serine racemase. By regulating the function of NMDA receptors, glial cells could potentially exert an important influence on synaptic transmission and synaptic plasticity.

A major goal of our current research is to understand the functional role of CD38 in the retina. CD38, an ectoenzyme originally thought to be exclusively localized to lymphocytes, is present in significant levels in the cell membranes of retinal Muller cells. We are testing the hypothesis that NAD+ released from retinal cells activates CD38 to produce second-messengers that modulate Ca2+ levels in retinal glia. Changes in the level of intracellular Ca2+ may alter the functional state of retinal glial cells, causing the release of signalling molecules or changing the expression of proteins that alter the phenotype of these cells. Such changes may contribute to the reactive nature of glial cells in responding to mechanical or traumatic insults and disease states.

Selected Publications