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.
1 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, WBSB 1001, Baltimore, MD 21205, USA.
2 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, WBSB 1001, Baltimore, MD 21205, USA.
3 Department of Electrical and Computer Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
4 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.
5 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, WBSB 1001, Baltimore, MD 21205, USA.