Ann Cornell-Bell

Noise sustained waves in subexcitable media: From chemical waves to brain waves

We discuss a novel type of spatiotemporal pattern that can be observed in subexcitable media when coupled to a thermal environment. These patterns have been recently observed in several different types of systems: a subexcitable photosensitive Belousov-Zhabotinsky reaction, hippocampal slices of rat brains, and astrocyte syncytium. In this paper, we introduce the basic concepts of subexcitable media, describe recent experimental observations in chemistry and neurophysiology, and put these observation into context with computer simulations. (c) 1998 American Institute of Physics.

Increased phase synchronization of spontaneous calcium oscillations in epileptic human versus normal rat astrocyte cultures

Stochastic synchronization analysis is applied to intracellular calcium oscillations in astrocyte cultures prepared from epileptic human temporal lobe. The same methods are applied to astrocyte cultures prepared from normal rat hippocampus. Our results indicate that phase-repulsive coupling in epileptic human astrocyte cultures is stronger, leading to an increased synchronization in epileptic human compared to normal rat astrocyte cultures.

Calcium signaling induced by adhesion mediates protein tyrosine phosphorylation and is independent of pHi.

Our goal was to evaluate early signaling events that occur as epithelial cells make initial contact with a substrate and to correlate them with phosphorylation. The corneal epithelium was chosen to study signaling events that occur with adhesion because it represents a simple system in which the tissue adheres to a basal lamina, is avascular, and is bathed by a tear film in which changes in the local environment are hypothesized to alter signaling. To perform these experiments we developed a novel adhesion assay to capture the changes in intracellular Ca2+ and pH that occur as a cell makes its initial contact with a substrate. The first transient cytosolic Ca2+ peak was detected only as the cell made contact with the substrate and was demonstrated using fluorimetric assays combined with live cell imaging. We demonstrated that this transient Ca2+ peak always preceded a cytoplasmic alkalization. When the intracellular environment was modified, the initial response was altered. Pretreatment with 1,2‐bis(o‐aminophenoxy)ethane‐N,N,N′N′‐tetraacetic acid (BAPTA), an intracellular chelator, inhibited Ca2+ mobilization, whereas benzamil altered the duration of the oscillations. Thapsigargin caused an initial Ca2+ release followed by a long attenuated response. An inositol triphosphate analog induced a large initial response, whereas heparin inhibited Ca2+ oscillations. Inhibitors of tyrosine phosphorylation did not alter the initial mobilization of cytosolic Ca2 but clearance of cytosolic Ca2+ was inhibited. Exposing corneal epithelial cells to BAPTA, benzamil, or thapsigargin also attenuated the phosphorylation of the focal adhesion protein paxillin. However, although heparin inhibited Ca2+ oscillations, it did not alter phosphorylation of paxillin. These studies demonstrate that the initial contact that a cell makes with a substrate modulates the intracellular environment, and that changes in Ca2+ mobilization can alter later signaling events such as the phosphorylation of specific adhesion proteins. These findings may have implications for wound repair and development. J. Cell. Physiol. 184:385–399, 2000.

Decoding calcium wave signaling

Publisher Summary This chapter reviews that intercellular calcium waves in astrocytes represent a phenomenon whereby a wave of increases in free cytosolic calcium concentration ([Ca 2+ ] i ) spreads from an initially stimulated cell across an astrocytic syncytium. Three key factors merged to trigger the discovery of calcium waves in the astrocyte syncytium. The first was finding that astrocytes possessed a full array of neurotransmitter receptors that operated on a millisecond time frame similar to that expected by neurons. The second contribution was the many technological advances made in time-lapse video microscopy, particularly involving the newly marketed confocal scanning laser microscope, which allowed longer recording periods free of phototoxicity. Lastly, most critical was the development of Ca 2+ sensitive fluorescent probes that were ion-specific that allowed precise quantification of changes in intracellular Ca 2+ . The chapter also explores that nitric oxide (NO)-mediated signaling mechanisms are involved, but only in some types of calcium waves, especially those triggered by mechanical stimulation. Neuronal activity also induces astrocytic calcium waves by stimulation of metabotropic glutamate receptors on astrocytes. In turn, glutamate release from astrocytes sustaining a calcium wave is capable of triggering neuronal activity.

Mathematical modeling of intracellular and intercellular calcium signaling

Publisher Summary This chapter reviews that billions of neurons, interconnected to a large network, perform numerous cognitive and regulatory tasks. Most work on the modeling of brain functions is based on the modelling of neuronal networks. The vast majority of cells in the brain, however, are nonneuronal cells or glial cells; about 90% of all brain cells are glial cells. Among the several types of glial cells, the astrocytes are known to carry out many important functions; several of them in interactions with neurons. The chapter highlights that astrocytes listen to neuronal chatter at the synapses and in turn can modulate neuronal dynamics at the same synapse or over some distance. As neurons fire, glutamate is released into the synaptic cleft that is partially lined by the metabotropic glutamate receptors of the synaptic astrocytes. Upon binding of glutamate to the astrocyte, inositol 1,4,5-triphosphate (IP 3 ) is released into the intracellular space. IP 3 in turn binds to the IP 3 receptor of the endoplasmic reticulum (ER) and Ca2 + is released from the ER into the cytosol. As described in more detail below, such Ca2 + release can occur in forms of intracellular Ca2 + waves. The Ca2 + wave can propagate across the cell membrane, through the extracellular space into adjacent astrocytes. Elevated Ca2 + concentrations in synaptic astrocytes generate extracellular glutamate that can modulate the neuronal synapse by generating additional inward currents. The chapter also reviews recent progress in mathematical modeling of intracellular and intercellular Ca2 + signaling in general, and in the context of astrocytes and their control of synaptic plasticity.