The limbic and central noradrenergic systems are sensitive to stress and demonstrate pathophysiology in individuals with mood and anxiety disorders. Neurons from the central nucleus of the amygdala (CeA) form synapses onto the dendrites of noradrenergic neurons of the locus coeruleus (LC) in the rostrolateral peri-coerulear area. The CeA-LC pathway is thought to contain GABA and corticotropin-releasing hormone (CRH), both of which have opposing effects on LC activity. The current study further characterized the CeA-LC pathway in vivo by examining extracellular electrophysiological LC activity during electrical and pharmacological manipulation of the CeA in halothane-anesthetized rats.
The majority of LC neurons exhibited an excitatory response to electrical CeA stimulation, with a small group of neurons responding with pure inhibition or antidromic activation. Pharmacological activation of the CeA confirmed excitatory responses to electrical stimulation, whereas pharmacological inactivation of the CeA had no effect on LC activity. Excitatory responses to electrical CeA stimulation were partially attenuated following ventricular infusions of the CRH antagonist, D-Phe-CRH, but were completely attenuated following infusions of the excitatory amino acid antagonist, kynurenic acid. Ventricular administration of kynurenic acid during electrical CeA stimulation also revealed an inhibitory period that simultaneously occurs with excitatory responses.
This study confirms previous findings suggesting that the CeA partially mediates excitatory responses via CRH. These findings further suggest that there is a glutamatergic component to excitatory responses following activation of the CeA. In addition, these data suggest that upon activation, the CeA provides a simultaneous inhibitory drive to LC neurons.
Collectively, these data provide additional support for an excitatory limbic input to neurons of the LC. The present data also suggest that the CeA may selectively modulate LC activity across its projection sites via the simultaneous inhibitory drive from the CeA. Activation of the CeA-LC pathway, particularly during stress responses, may be critical for noradrenergic modulation of cortical and limbic areas involved in attention, emotional learning, and responses to stressful stimuli.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07082008-115333 |
| Date | 28 September 2008 |
| Creators | Ramsooksingh, Meera Devi |
| Contributors | Susan R. Sesack, Anthony A. Grace, Linda Rinaman |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-07082008-115333/ |
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