title: Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex.
abstract: Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This priming effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex.
authors.affiliation: Department of Pharmacology, School of Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan; Keio Advanced Research Center for Water Biology and Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan; Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Kanagawa, 240-8501, Japan. Electronic address: mnuriya@z2.keio.jp.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Nuriya
authors.affiliation: Department of Pharmacology, School of Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan.
authors.forename: Miyabi
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Pharmacology, School of Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan; Keio Advanced Research Center for Water Biology and Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yasui
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine
keywords: Astrocyte; Calcium; Cerebral cortex; Norepinephrine