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Cerebral Cortex Advance Access published online on March 27, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn040
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Locus Coeruleus {alpha}-Adrenergic–Mediated Activation of Cortical Astrocytes In Vivo

Lane K. Bekar, Wei He and Maiken Nedergaard

Division of Glial Disease and Therapeutics, Department of Neurosurgery, University of Rochester, Rochester, NY 14642, USA

Address correspondence to Lane K. Bekar, PhD, Division of Glial Disease and Therapeutics, 601 Elmwood Avenue, Rochester, New York 14642, USA. Email: Lane_Bekar{at}URMC.Rochester.edu.

The locus coeruleus (LC) provides the sole source of norepinephrine (NE) to the cortex for modulation of cortical synaptic activity in response to salient sensory information. NE has been shown to improve signal-to-noise ratios, sharpen receptive fields and function in learning, memory, and cognitive performance. Although LC-mediated effects on neurons have been addressed, involvement of astrocytes has thus far not been demonstrated in these neuromodulatory functions. Here we show for the 1st time in live mice, that astrocytes exhibit rapid Ca2+ increases in response to electrical stimulation of the LC. Additionally, robust peripheral stimulation known to result in phasic LC activity leads to Ca2+ responses in astrocytes throughout sensory cortex that are independent of sensory-driven glutamate-dependent pathways. Furthermore, the astrocytic Ca2+ transients are competitively modulated by {alpha}2-specific agonist/antagonist combinations known to impact LC output, are sensitive to the LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, and are inhibited locally by an {alpha}-adrenergic antagonist. Future investigations of LC function must therefore consider the possibility that LC neuromodulatory effects are in part derived from activation of astrocytes.

Key Words: calcium transients • footshock • somatosensory • LC • metabotropic glutamate receptor • neuromodulator


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