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The Journal of Neuroscience, November 7, 2007, 27(45):12358-12366; doi:10.1523/JNEUROSCI.2007-07.2007

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Behavioral/Systems/Cognitive
Noradrenergic Modulation of Basolateral Amygdala Neuronal Activity: Opposing Influences of -2 and ß Receptor Activation

Deanne M. Buffalari¹ and Anthony A. Grace^1,2

¹Department of Neuroscience and ²Departments of Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Correspondence should be addressed to Anthony A. Grace, Department of Neuroscience, A210 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260. Email: graceaa{at}pitt.edu

Substantial data exists demonstrating the importance of the amygdala and the locus ceruleus (LC) in responding to stress, aversive memory formation, and the development of stress-related disorders; however, little is known about the effects of norepinephrine (NE) on amygdala neuronal activity in vivo. The basolateral nucleus of the amygdala (BLA) receives dense NE projections from the LC, NE increases in the BLA in response to stress, and the BLA can also modulate the LC via reciprocal projections. These experiments examined the effects of noradrenergic agents on spontaneous and evoked responses of BLA neurons. NE iontophoresis inhibited spontaneous firing and decreased the responsiveness of BLA neurons to electrical stimulation of entorhinal cortex and sensory association cortex (Te3). Confirmed BLA projection neurons exhibited exclusively inhibitory responses to NE. Systemic administration of propranolol, a ß-receptor antagonist, decreased the spontaneous firing rate and potentiated the NE-evoked inhibition of BLA neurons. In addition, iontophoresis of the -2 agonist clonidine, footshock administration, and LC stimulation mimicked the effects of NE iontophoresis on spontaneous activity. Furthermore, the effects of LC stimulation were partially blocked by systemic administration of 2 and ß receptor antagonists. This is the first study to demonstrate the actions of directly applied and stimulus-evoked NE in the BLA in vivo, and provides a mechanism by which ß receptors can mediate the important behavioral consequences of NE within the BLA. The interaction between these two structures is particularly relevant with regard to their known involvement in stress responses and stress-related disorders.

Key words: amygdala; norepinephrine; footshock; locus ceruleus; ß receptors; -2 receptors

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Received Nov. 20, 2006; revised Sept. 11, 2007; accepted Sept. 11, 2007.

Correspondence should be addressed to Anthony A. Grace, Department of Neuroscience, A210 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260. Email: graceaa{at}pitt.edu

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