Norepinephrine from the Locus Coeruleus Regulates Microglia Dynamics During Wakefulness

  • Yaling Hu
  • Peng Shi
  • Zhihua GaoEmail author

Microglia, the brain’s “busy bees”, continuously survey the microenvironment by extending and retracting their ramified processes to maintain brain homeostasis [1, 2]. Upon disease or injury, microglia quickly transform their morphology and extend their processes towards the disease/injury sites to clear damage [2]. The mechanisms underlying the high motility of microglial processes and the rapid morphological transformation of microglia have been extensively investigated. However, studies on microglial dynamics in vivo have predominantly been carried out in anesthetized animals, and how microglia behave under awake conditions remained unknown. Using two-photon microscopy to track microglia dynamics in awake mice, two independent studies published recently [3, 4] have demonstrated that during wakefulness, microglia exhibit shorter arborization, reduced motility, and diminished responsiveness to injury compared to those under anesthesia. Moreover, both studies showed that...



This work was supported by the National Natural Science Foundation of China (31671057) and the Fundamental Research Funds for the Central Universities (2019FZA7009).


  1. 1.
    Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005, 308: 1314–1318.PubMedCrossRefGoogle Scholar
  2. 2.
    Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 2005, 8: 752–758.PubMedCrossRefGoogle Scholar
  3. 3.
    Stowell RD, Sipe GO, Dawes RP, Batchelor HN, Lordy KA, Whitelaw BS, et al. Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex. Nat Neurosci 2019, 22: 1782–1792.PubMedCrossRefGoogle Scholar
  4. 4.
    Liu YU, Ying Y, Li Y, Eyo UB, Chen T, Zheng J, et al. Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nat Neurosci 2019, 22: 1771–1781.PubMedCrossRefGoogle Scholar
  5. 5.
    Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O’Keeffe S, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 2014, 34: 11929–11947.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Gyoneva S, Traynelis SF. Norepinephrine modulates the motility of resting and activated microglia via different adrenergic receptors. J Biol Chem 2013, 288: 15291–15302.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Wu Y, Dissing-Olesen L, MacVicar BA, Stevens B. Microglia: dynamic mediators of synapse development and plasticity. Trends Immunol 2015, 36: 605–613.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Pocock JM, Kettenmann H. Neurotransmitter receptors on microglia. Trends Neurosci 2007, 30: 527–535.PubMedCrossRefGoogle Scholar
  9. 9.
    Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D, et al. Locus ceruleus controls Alzheimer’s disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci U S A 2010, 107: 6058–6063.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Kvetnansky R, Sabban EL, Palkovits M. Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev 2009, 89: 535–606.PubMedCrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2020

Authors and Affiliations

  1. 1.Neuroscience Research Center and Department of Neurology, The Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhouChina
  2. 2.Department of Cardiology, The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina

Personalised recommendations