Norepinephrine Controls Astroglial Responsiveness to Local Circuit Activity

• Published in: Neuron (Cambridge, Mass.) Vol. 82; no. 6; pp. 1263 - 1270
• Main Authors: Paukert, Martin, Agarwal, Amit, Cha, Jaepyeong, Doze, Van A., Kang, Jin U., Bergles, Dwight E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18-06-2014; Elsevier Limited
• Subjects: Action Potentials - physiology; Animals; Astrocytes - secretion; Behavior; Medical research; Mice; Mice, Transgenic; Nerve Net - secretion; Norepinephrine - secretion; Optics; Photic Stimulation - methods; Rodents; Visual Cortex - secretion
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2014.04.038

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 Ca2+ 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 Ca2+ 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.
•Ca2+ transients in Bergmann glia during locomotion depend on animal state of arousal•Norepinephrine induces Ca2+ elevations in Bergmann glia during locomotion•Locomotion-induced norepinephrine release activates astrocytes in visual cortex•Norepinephrine enhances the sensitivity of astrocytes to local circuit activity
Paukert et al. show that norepinephrine release during locomotion triggers widespread activation of astroglia in the brain. In visual cortex, this modulation enables astrocytes to respond to visual stimulation, indicating that norepinephrine controls the sensitivity of astrocytes to sensory input.