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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 26, 2008, 28(48):12927-12937; doi:10.1523/JNEUROSCI.2887-08.2008

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 Google Scholar Google Scholar Articles by Kirby, L. G. Articles by Beck, S. G. Search for Related Content PubMed PubMed Citation Articles by Kirby, L. G. Articles by Beck, S. G.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Corticotropin-Releasing Factor Increases GABA Synaptic Activity and Induces Inward Current in 5-Hydroxytryptamine Dorsal Raphe Neurons

Lynn G. Kirby,¹ Emily Freeman-Daniels,¹ Julia C. Lemos,² John D. Nunan,¹ Christophe Lamy,² Adaure Akanwa,² and Sheryl G. Beck²

¹Department of Anatomy and Cell Biology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and ²Department of Anesthesiology, University of Pennsylvania School of Medicine and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104

Correspondence should be addressed to Dr. Lynn G. Kirby, Department of Anatomy and Cell Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140. Email: lkirby{at}temple.edu

Stress-related psychiatric disorders such as anxiety and depression involve dysfunction of the serotonin [5-hydroxytryptamine (5-HT)] system. Previous studies have found that the stress neurohormone corticotropin-releasing factor (CRF) inhibits 5-HT neurons in the dorsal raphe nucleus (DRN) in vivo. The goals of the present study were to characterize the CRF receptor subtypes (CRF-R1 and -R2) and cellular mechanisms underlying CRF–5-HT interactions. Visualized whole-cell patch-clamp recording techniques in brain slices were used to measure spontaneous or evoked GABA synaptic activity in DRN neurons of rats and CRF effects on these measures. CRF-R1 and -R2-selective agonists were bath applied alone or in combination with receptor-selective antagonists. CRF increased presynaptic GABA release selectively onto 5-HT neurons, an effect mediated by the CRF-R1 receptor. CRF increased postsynaptic GABA receptor sensitivity selectively in 5-HT neurons, an effect to which both receptor subtypes contributed. CRF also had direct effects on DRN neurons, eliciting an inward current in 5-HT neurons mediated by the CRF-R2 receptor and in non-5-HT neurons mediated by the CRF-R1 receptor. These results indicate that CRF has direct membrane effects on 5-HT DRN neurons as well as indirect effects on GABAergic synaptic transmission that are mediated by distinct receptor subtypes. The inhibition of 5-HT DRN neurons by CRF in vivo may therefore be primarily an indirect effect via stimulation of inhibitory GABA synaptic transmission. These results regarding the cellular mechanisms underlying the complex interaction between CRF, 5-HT, and GABA systems could contribute to the development of novel treatments for stress-related psychiatric disorders.

Key words: serotonin; stress; urocortin II; antalarmin; antisauvagine-30; IPSC

---

Received June 23, 2008; revised Oct. 6, 2008; accepted Oct. 9, 2008.

Correspondence should be addressed to Dr. Lynn G. Kirby, Department of Anatomy and Cell Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140. Email: lkirby{at}temple.edu

This article has been cited by other articles:

				J. R. Homberg and C. Contet Deciphering the Interaction of the Corticotropin-Releasing Factor and Serotonin Brain Systems in Anxiety-Related Disorders J. Neurosci., November 4, 2009; 29(44): 13743 - 13745. [Full Text] [PDF]

				J. M. Leitch, L. T. Jensen, S. D. Bouldin, C. E. Outten, P. J. Hart, and V. C. Culotta Activation of Cu,Zn-Superoxide Dismutase in the Absence of Oxygen and the Copper Chaperone CCS J. Biol. Chem., August 14, 2009; 284(33): 21863 - 21871. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help