NEUROLIGAND RECEPTOR HETEROGENEITY AMONG ASTROGLIA

Astroglia are remarkedly diverse cells with respect to their pharmacol ogical responsiveness and the processes regulated by neuroligand recep tors. The results of single cell analyses indicate that astroglia cont inue to diversify in vitro. For example, the two daughter cells of a s ingle division can exhibit qualitatively distinct responses to neuroli gand application. These findings indicate that in contrast to most cel ls that ''lock'' their neuroligand receptor phenotype early in develop ment, astroglia exhibit unusual plasticity. It is possible that this p lasticity is necessary for immature astrocytes to respond to a changin g neuronal environment during development. Interestingly, the increase in astroglial calcium following addition of neuroligands tends to ori ginate from a localized area of the cell and then spreads as a wave th at moves through the cell in a nondecremental manner. In situations in which astroglia are connected by gap junctions, the wave of calcium i n one cell readily moves into the second without any obvious decrease in magnitude. Furthermore, astroglial calcium responses occur in an '' all-or-none'' manner reminiscent of neuronal action potentials. That i s, the magnitude of an astroglial cell's calcium response appears rela tively independent of the concentration of the ligand used or the dens ity of receptors present on the cell. However, the probability of an a stroglial cell responding to a given neuroligand is related to the den sity of receptors expressed and the concentration of the neuroligand a pplied. These characteristics suggest that, like neurons, signals rece ived by an astrocyte are integrated and that when a threshold is reach ed the cell responds with a localized response that then propagates th rough that cell and into adjacent cells in a nondecremental manner. In neurons this is accomplished via depolarizations leading to action po tentials and release of neurotransmitters. In astrocytes, distant sign aling appears to occur via an ''all-or-none'' release of calcium, whic h then propagates through the cell and neighboring cells as a calcium wave. Our recent findings that neuroligands can modulate the opening a nd closing of astrocytic gap junctions suggest that specific pathways of astrocytic communication may exist. Overall, it is becoming evident that neuronal-glial signaling may be far more complex than previously imagined.