Abstract
It is well-established that astrocytes respond to norepinephrine with cytosolic calcium rises in various brain areas, such as hippocampus or neocortex. However, less is known about the effect of norepinephrine on olfactory bulb astrocytes. In the present study, we used confocal calcium imaging and immunohistochemistry in mouse brain slices of the olfactory bulb, a brain region with a dense innervation of noradrenergic fibers, to investigate the calcium signaling evoked by norepinephrine in astrocytes. Our results show that application of norepinephrine leads to a cytosolic calcium rise in astrocytes which is independent of neuronal activity and mainly mediated by PLC/IP3-dependent internal calcium release. In addition, store-operated calcium entry (SOCE) contributes to the late phase of the response. Antagonists of both α1- and α2-adrenergic receptors, but not β-receptors, largely reduce the adrenergic calcium response, indicating that both α-receptor subtypes mediate norepinephrine-induced calcium transients in olfactory bulb astrocytes, whereas β-receptors do not contribute to the calcium transients.
Highlights
Norepinephrine is one of the major neuromodulators in the mammalian central nervous system
We showed that norepinephrine induced a rise in cytosolic calcium concentration in mouse olfactory bulb astrocytes in situ
The study was performed on brain slices obtained from animals at an age of 1–3 weeks and we cannot exclude changes in adrenergic calcium signaling in olfactory bulb astrocytes during adolescent development and aging
Summary
Norepinephrine is one of the major neuromodulators in the mammalian central nervous system It is involved in a variety of vital cognitive functions such as memory and attention (Berridge and Waterhouse, 2003; Aston-Jones and Cohen, 2005). Its widespread neuronal projections innervate many different brain regions such as the neocortex, amygdala, hippocampus, and hypothalamus. They reach the main olfactory bulb, where ≈40% of LC neurons project to (Shipley et al, 1985). Noradrenergic input to the main olfactory bulb is part of the centrifugal innervation and plays a key role in odor learning, recognition, and recall (Linster et al, 2011). In accordance with the noradrenergic fiber distribution, each of the three major subtypes, α1-, α2-, and β-receptors, are expressed in multiple layers of the olfactory bulb, and distinct main olfactory bulb neurons seem to express
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