Neuron-glia signaling via alpha(1) adrenoceptor-mediated Ca2+ release in Bergmann glial cells in situ

Adrenoceptors were among the first neurotransmitter receptors identified in glial cells, but it is not known whether these receptors meditate glial re sponses during neuronal activity. We show that repetitive nerve activity ev oked a rise of intracellular calcium in Bergmann glia and neighboring Purki nje neurons of cerebellar slices of mice. The glial but not the neuronal ca lcium transient persisted during block of ionotropic and metabotropic gluta mate receptors. In contrast, the glial calcium response was abolished by cy clopiazonic acid and prazosin; however, prazosin affected neither the inwar d current nor the resulting depolarization that accompanied the stimulus-in duced glial calcium transients. The glial depolarization was attenuated by 38% by the mixture of glutamate receptor blockers, which abolished the evok ed neuronal depolarization and afterhyperpolarization. Ba2+ reduced the gli al currents by 66% without affecting the concomitant calcium transients. In the presence of Ba2+, the mixture of glutamate receptor blockers exerted n o effect on the glial inward current or calcium rise. Furthermore, Ba2+ gre atly potentiated both the activity-related Purkinje cell inward current and the accompanying neuronal calcium rises. The results indicate that release of noradrenaline from afferent fibers activates a glial alpha(1) adrenocep tor that promotes calcium release from intracellular stores. Glial calcium rises are known to stimulate a diversity of processes such as transmitter r elease, energy metabolism, or proliferation. Thus the adrenoceptor-mediated mechanism described here is well suited for feedback modulation of neurona l function that is independent of glutamate.