Date of Award
Doctor of Philosophy
Zoology and Genetics
Philip G. Haydon
Drena L. Dobbs
The traditional view of the central nervous system (CNS) in which only neurons are capable of active intercellular signaling while glial cells merely provide structural and trophic support to neurons, has been challenged by a number of new findings. Recent evidence shows that astrocytes, a subtype of glial cells, participate in inter-astrocyte signaling by using variations in their cytosolic Ca2+ levels (Cornell-Beil et al., 1990; Charles et al., 1991; Finkbeiner et al., 1992; Duffy and MacVicar, 1995). Neuronal activity can trigger these Ca2+ increases in astrocytes indicating that neurons can signal to astrocytes (Dani et al., 1992; Porter and McCarthy, 1996; Pasti et al., 1997). Finally, the demonstration that Ca2+ elevations in astrocytes evoke glutamate release from them and subsequent glutamate-dependent Ca2+ elevations in adjacent neurons, have raised the exciting possibility that astrocytes may in turn, signal back to neurons (Nedergaard et al., 1994; Parpura et al., 1994; Charles et al., 1994; Hassinger et al., 1995; Pasti et al., 1997; Bezzi et al., 1998);Although the existence of astrocyte to neuron signaling has been firmly established by these Ca2+ imaging studies, the physiological consequences of this signaling have not been elucidated. The work presented in this dissertation, provides electrophysiological evidence for the astrocyte-neuron signaling and demonstrates that stimulation of astrocytes leads to Ca2+ increases in astrocytes which modulates neuronal currents and synaptic transmission in hippocampal cultured new-ons (Araque et al., 1998a,b). A variety of stimuli that increase the intracellular Ca2+ levels in astrocytes, such as mechanical or electrical stimulation and application of the neuroligand prostaglandin E2, generate a glutamate-dependent slow inward current (SIC) mediated through the NMDA and non-NMDA glutamate receptors and/or an increase in the frequency of the miniature synaptic currents through the NMDA receptors in adjacent neurons. Additionally, stimulation of astrocytes transiently reduces the amplitude of the action potential-evoked postsynaptic current mediated through the metabotropic glutamate receptors;This work proposes a new view of the nervous system in which neurons and astrocytes exist as a network in which bidirectional communication takes place.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Rita Prabhakar Sanzgiri
Sanzgiri, Rita Prabhakar, "Physiological consequences of astrocyte-to-neuron signaling " (1998). Retrospective Theses and Dissertations. 11888.