Neuroligand receptor heterogeneity among astroglia.

Astroglia are remarkedly diverse cells with respect to their pharmacological responsiveness and the processes regulated by neuroligand receptors. The results of single cell analyses indicate that astroglia continue to diversify in vitro. For example, the two daughter cells of a single division can exhibit qualitatively distinct responses to neuroligand application. These findings indicate that in contrast to most cells that "lock" their neuroligand receptor phenotype early in development, astroglia exhibit unusual plasticity. It is possible that this plasticity is necessary for immature astrocytes to respond to a changing neuronal environment during development. Interestingly, the increase in astroglial calcium following addition of neuroligands tends to originate from a localized area of the cell and then spreads as a wave that moves through the cell in a nondecremental manner. In situations in which astroglia are connected by gap junctions, the wave of calcium in 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 is, the magnitude of an astroglial cell's calcium response appears relatively independent of the concentration of the ligand used or the density of receptors present on the cell. However, the probability of an astroglial cell responding to a given neuroligand is related to the density of receptors expressed and the concentration of the neuroligand applied. These characteristics suggest that, like neurons, signals received by an astrocyte are integrated and that when a threshold is reached the cell responds with a localized response that then propagates through that cell and into adjacent cells in a nondecremental manner. In neurons this is accomplished via depolarizations leading to action potentials and release of neurotransmitters. In astrocytes, distant signaling appears to occur via an "all-or-none" release of calcium, which then propagates through the cell and neighboring cells as a calcium wave. Our recent findings that neuroligands can modulate the opening and 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.