title: Norepinephrine controls astroglial responsiveness to local circuit activity.
abstract: Astrocytes perform crucial supportive functions, including neurotransmitter clearance, ion buffering, and metabolite delivery. They can also influence blood flow and neuronal activity by releasing gliotransmitters in response to intracellular Ca(2+) transients. However, little is known about how astrocytes are engaged during different behaviors in vivo. Here we demonstrate that norepinephrine primes astrocytes to detect changes in cortical network activity. We show in mice that locomotion triggers simultaneous activation of astrocyte networks in multiple brain regions. This global stimulation of astrocytes was inhibited by alpha-adrenoceptor antagonists and abolished by depletion of norepinephrine from the brain. Although astrocytes in visual cortex of awake mice were rarely engaged when neurons were activated by light stimulation alone, pairing norepinephrine release with light stimulation markedly enhanced astrocyte Ca(2+) signaling. Our findings indicate that norepinephrine shifts the gain of astrocyte networks according to behavioral state, enabling astrocytes to respond to local changes in neuronal activity.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, WBSB 1001, Baltimore, MD 21205, USA. Electronic address: paukertm@uthscsa.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Paukert
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, WBSB 1001, Baltimore, MD 21205, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Department of Electrical and Computer Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Jaepyeong
authors.initials: J
authors.lastname: Cha
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road Stop 9061, Grand Forks, ND 58202, USA.
authors.forename: Van A
authors.initials: VA
authors.lastname: Doze
authors.affiliation: Department of Electrical and Computer Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Jin U
authors.initials: JU
authors.lastname: Kang
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, WBSB 1001, Baltimore, MD 21205, USA. Electronic address: dbergles@jhmi.edu.
authors.forename: Dwight E
authors.initials: DE
authors.lastname: Bergles
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods*; D014793:Visual Cortex / Q000378:metabolism
chemical_list: D009638:Norepinephrine