QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 27, 2004, 24(43):9703-9713; doi:10.1523/JNEUROSCI.2830-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Jedema, H. P. Articles by Grace, A. A. Search for Related Content PubMed PubMed Citation Articles by Jedema, H. P. Articles by Grace, A. A.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Corticotropin-Releasing Hormone Directly Activates Noradrenergic Neurons of the Locus Ceruleus Recorded In Vitro

Hank P. Jedema¹ and Anthony A. Grace^1,2,3

Departments of ¹Neuroscience, ²Psychiatry, and ³Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

The neuropeptide corticotropin-releasing hormone (CRH) activates locus ceruleus (LC) neurons, thereby increasing norepinephrine levels throughout the CNS. Despite anatomical and physiological evidence for CRH innervation of the LC, the mechanism of CRH-evoked activation of LC neurons is unknown. Moreover, given the apparent absence of mRNA for CRH receptors in LC neurons, the exact location of action of CRH within the cerulear region is debated. Using in vitro intracellular recordings from rat brainstem, we examined whether CRH exerts a direct effect on LC neurons and which ionic currents are likely affected by CRH. We demonstrate that CRH dose-dependently increases the firing rate of LC neurons through a direct (TTX- and cadmium-insensitive) mechanism by decreasing a potassium conductance. The CRH-evoked activation of LC neurons is, at least in part, mediated by CRH₁ receptors and a cAMP-dependent second messenger system. These data provide additional support that CRH functions as an excitatory neurotransmitter in the LC and the hypothesis that dysfunction of the CRH peptidergic and noradrenergic systems observed in patients with mood and anxiety disorders are functionally related.

Key words: cathecholamine; ceruleus; corticotropin; CRF; intracellular; norepinephrine (noradrenaline)

---

Received July 14, 2004; revised August 27, 2004; accepted September 8, 2004.

This article has been cited by other articles:

				L. G. Kirby, E. Freeman-Daniels, J. C. Lemos, J. D. Nunan, C. Lamy, A. Akanwa, and S. G. Beck Corticotropin-Releasing Factor Increases GABA Synaptic Activity and Induces Inward Current in 5-Hydroxytryptamine Dorsal Raphe Neurons J. Neurosci., November 26, 2008; 28(48): 12927 - 12937. [Abstract] [Full Text] [PDF]

				B. Roozendaal, G. Schelling, and J. L. McGaugh Corticotropin-Releasing Factor in the Basolateral Amygdala Enhances Memory Consolidation via an Interaction with the {beta}-Adrenoceptor-cAMP Pathway: Dependence on Glucocorticoid Receptor Activation J. Neurosci., June 25, 2008; 28(26): 6642 - 6651. [Abstract] [Full Text] [PDF]

				M. J. Wanat, F. W. Hopf, G. D. Stuber, P. E. M. Phillips, and A. Bonci Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih J. Physiol., April 15, 2008; 586(8): 2157 - 2170. [Abstract] [Full Text] [PDF]

				B. A. S. Reyes, R. J. Valentino, and E. J. Van Bockstaele Stress-Induced Intracellular Trafficking of Corticotropin-Releasing Factor Receptors in Rat Locus Coeruleus Neurons Endocrinology, January 1, 2008; 149(1): 122 - 130. [Abstract] [Full Text] [PDF]

				K. L. Smith, M. Patterson, W. S. Dhillo, S. R. Patel, N. M. Semjonous, J. V. Gardiner, M. A. Ghatei, and S. R. Bloom Neuropeptide S Stimulates the Hypothalamo-Pituitary-Adrenal Axis and Inhibits Food Intake Endocrinology, July 1, 2006; 147(7): 3510 - 3518. [Abstract] [Full Text] [PDF]

				S. Traver, M. Marien, E. Martin, E. C. Hirsch, and P. P. Michel The Phenotypic Differentiation of Locus Ceruleus Noradrenergic Neurons Mediated by Brain-Derived Neurotrophic Factor Is Enhanced by Corticotropin Releasing Factor through the Activation of a cAMP-Dependent Signaling Pathway Mol. Pharmacol., July 1, 2006; 70(1): 30 - 40. [Abstract] [Full Text] [PDF]

				E. W. Hillhouse and D. K. Grammatopoulos The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology Endocr. Rev., May 1, 2006; 27(3): 260 - 286. [Abstract] [Full Text] [PDF]

				M.-H. Han, C. A. Bolanos, T. A. Green, V. G. Olson, R. L. Neve, R.-J. Liu, G. K. Aghajanian, and E. J. Nestler Role of cAMP response element-binding protein in the rat locus ceruleus: regulation of neuronal activity and opiate withdrawal behaviors. J. Neurosci., April 26, 2006; 26(17): 4624 - 4629. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help