Neuron–Glia Signaling via α₁Adrenoceptor-Mediated Ca²⁺Release in Bergmann Glial CellsIn Situ

Abstract

Adrenoceptors were among the first neurotransmitter receptors identified in glial cells, but it is not known whether these receptors meditate glial responses during neuronal activity. We show that repetitive nerve activity evoked a rise of intracellular calcium in Bergmann glia and neighboring Purkinje neurons of cerebellar slices of mice. The glial but not the neuronal calcium transient persisted during block of ionotropic and metabotropic glutamate receptors. In contrast, the glial calcium response was abolished by cyclopiazonic acid and prazosin; however, prazosin affected neither the inward current nor the resulting depolarization that accompanied the stimulus-induced glial calcium transients. The glial depolarization was attenuated by 38% by the mixture of glutamate receptor blockers, which abolished the evoked neuronal depolarization and afterhyperpolarization. Ba(2+) reduced the glial currents by 66% without affecting the concomitant calcium transients. In the presence of Ba(2+), the mixture of glutamate receptor blockers exerted no effect on the glial inward current or calcium rise. Furthermore, Ba(2+) greatly 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) adrenoceptor that promotes calcium release from intracellular stores. Glial calcium rises are known to stimulate a diversity of processes such as transmitter release, energy metabolism, or proliferation. Thus the adrenoceptor-mediated mechanism described here is well suited for feedback modulation of neuronal function that is independent of glutamate.

Brief Bursts of Parallel Fiber Activity Trigger Calcium Signals in Bergmann Glia

“…We found that blocking ␣1 adrenoceptors does not alter BG calcium signals, suggesting that the release of noradrenaline by locus ceruleus fibers is not required for BG calcium signals (Kulik et al, 1999). Similarly, the insensitivity of BG calcium signals to the blockade of NO synthase indicates that BG calcium signals do not require NO release (Matyash et al, 2001).…”

“…One study reported that BG calcium increases evoked by granule layer stimulation were blocked by the ␣1 adrenoceptor antagonist prazosin (Kulik et al, 1999), suggesting that activity in afferent fibers from the locus ceruleus trigger BG calcium signals. In contrast to these studies, calcium signals evoked by PF stimulation were not affected by prazosin (Fig.…”

“…BGs express high levels of glutamate transporters (Chaudhry et al, 1995;Ottersen et al, 1997) and are therefore particularly effective in confining glutamate to activated synapses (Bergles et al, 1997;Clark and Barbour, 1997;Huang and Bordey, 2004). In addition, exogenous agonist application (Muller et al, 1992;Kirischuk et al, 1995;Kirischuk et al, 1996) and synaptic activation (Grosche et al, 1999) via the release of nitric oxide (NO) (Matyash et al, 2001) or noradrenaline (Kulik et al, 1999) can lead to calcium increases in BGs. Although activation of metabotropic glutamate receptors (mGluRs) and purinergic receptors (P2Rs) via synaptically released glutamate and ATP are mediators of calcium signaling in other types of glia (Porter and McCarthy, 1996;Pasti et al, 1997;Newman, 2005), no such role has been has been described in BGs.…”

Stress Impairs α1A Adrenoceptor-Mediated Noradrenergic Facilitation of GABAergic Transmission in the Basolateral Amygdala

“…Studies in other brain regions or cell types have shown that a 1 adrenoceptors are coupled to PLC via a G-protein, and can increase the intracellular calcium concentration [Ca 2+ ] i by mobilizing Ca 2+ from intracellular stores, as well as by increasing the Ca 2+ influx (Schwinn et al, 1991;Wu et al, 1992;Cohen and Almazan, 1993;Lepretre et al, 1994;Kulik et al, 1999). However, certain effects of a 1A activation involve signaling pathways that are independent of PLC activation and intracellular Ca 2+ rise (Berts et al, 1999).…”

Mice expressing the α1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

“…a 1 -AR activation can increase the action potential-dependent inhibitory postsynaptic potentials in pyramidal neurons of the hippocampus by depolarizing surrounding inhibitory interneurons (Bergles et al 1996). a 1 -ARs may also affect many brain functions via non-neuronal mechanisms since they may be localized to glial cells (Kulik et al 1999). However, the lack of specific antibodies has also prohibited the determination of exact cell types that express a 1 -ARs.…”