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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

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 ISI 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 ISI Web of Science (77) Citing Articles via Google Scholar Google Scholar Articles by Feng, J. Articles by Yan, Z. Search for Related Content PubMed PubMed Citation Articles by Feng, J. Articles by Yan, Z.

 Previous Article  |  Next Article 

The Journal of Neuroscience, September 1, 2001, 21(17):6502-6511

Serotonin Receptors Modulate GABA_A Receptor Channels through Activation of Anchored Protein Kinase C in Prefrontal Cortical Neurons

Jian Feng, Xiang Cai, Jinghui Zhao, and Zhen Yan

Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214

Serotonergic neurotransmission in prefrontal cortex (PFC) has long been known to play a key role in regulating emotion and cognition under normal and pathological conditions. However, the cellular mechanisms by which this regulation occurs are unclear. In this study, we examined the impact of serotonin on GABA_A receptor channels in PFC pyramidal neurons using combined patch-clamp recording, biochemical, and molecular approaches. Application of serotonin produced a reduction of postsynaptic GABA_A receptor currents. Although multiple 5-HT receptors were coexpressed in PFC pyramidal neurons, the serotonergic modulation of GABA-evoked currents was mimicked by the 5-HT₂-class agonist ()-2,5-dimethoxy-4-iodoamphetamine and blocked by 5-HT₂ antagonists risperidone and ketanserin, indicating the mediation by 5-HT₂ receptors. Inhibiting phospholipase C blocked the 5-HT₂ inhibition of GABA_A currents, as did dialysis with protein kinase C (PKC) inhibitory peptide. Moreover, activation of 5-HT₂ receptors in PFC slices increased the in vitro kinase activity of PKC toward GABA_A receptor 2 subunits. Disrupting the interaction of PKC with its anchoring protein RACK1 (receptor for activated C kinase) eliminated the 5-HT₂ modulation of GABA_A currents, suggesting that RACK1-mediated targeting of PKC to the vicinity of GABA_A receptors is required for the serotonergic signaling. Together, our results show that activation of 5-HT₂ receptors in PFC pyramidal neurons inhibits GABA_A currents through phosphorylation of GABA_A receptors by the activation of anchored PKC. The suppression of GABAergic signaling provides a novel mechanism for serotonergic modulation of PFC neuronal activity, which may underlie the actions of many antidepressant drugs.

Key words: prefrontal cortex; serotonin receptors; GABA_A receptors; phosphorylation; anchoring proteins; RACK1; patch-clamp; single-cell mRNA profiling

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/21176502-10$05.00/0

This article has been cited by other articles:

				N. Wanaverbecq, A. Semyanov, I. Pavlov, M. C. Walker, and D. M. Kullmann Cholinergic Axons Modulate GABAergic Signaling among Hippocampal Interneurons via Postsynaptic {alpha}7 Nicotinic Receptors J. Neurosci., May 23, 2007; 27(21): 5683 - 5693. [Abstract] [Full Text] [PDF]

				Z. Gu, Q. Jiang, and Z. Yan RGS4 Modulates Serotonin Signaling in Prefrontal Cortex and Links to Serotonin Dysfunction in a Rat Model of Schizophrenia Mol. Pharmacol., April 1, 2007; 71(4): 1030 - 1039. [Abstract] [Full Text] [PDF]

				E. A. Hackler, G. H. Turner, P. J. Gresch, S. Sengupta, A. Y. Deutch, M. J. Avison, J. C. Gore, and E. Sanders-Bush 5-Hydroxytryptamine2C Receptor Contribution to m-Chlorophenylpiperazine and N-Methyl-beta-carboline-3-carboxamide-Induced Anxiety-Like Behavior and Limbic Brain Activation J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1023 - 1029. [Abstract] [Full Text] [PDF]

				G. Chen, J. T. Kittler, S. J. Moss, and Z. Yan Dopamine D3 Receptors Regulate GABAA Receptor Function through a Phospho-Dependent Endocytosis Mechanism in Nucleus Accumbens J. Neurosci., March 1, 2006; 26(9): 2513 - 2521. [Abstract] [Full Text] [PDF]

				J. T. Kittler, G. Chen, S. Honing, Y. Bogdanov, K. McAinsh, I. L. Arancibia-Carcamo, J. N. Jovanovic, M. N. Pangalos, V. Haucke, Z. Yan, et al. Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission PNAS, October 11, 2005; 102(41): 14871 - 14876. [Abstract] [Full Text] [PDF]

				E. Y. Yuen, Q. Jiang, J. Feng, and Z. Yan Microtubule Regulation of N-Methyl-D-aspartate Receptor Channels in Neurons J. Biol. Chem., August 19, 2005; 280(33): 29420 - 29427. [Abstract] [Full Text] [PDF]

				E. Y. Yuen, Q. Jiang, P. Chen, Z. Gu, J. Feng, and Z. Yan Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism J. Neurosci., June 8, 2005; 25(23): 5488 - 5501. [Abstract] [Full Text] [PDF]

				H.-Y. Wu, E. Y. Yuen, Y.-F. Lu, M. Matsushita, H. Matsui, Z. Yan, and K. Tomizawa Regulation of N-Methyl-D-aspartate Receptors by Calpain in Cortical Neurons J. Biol. Chem., June 3, 2005; 280(22): 21588 - 21593. [Abstract] [Full Text] [PDF]

				J. P. Tyszkiewicz and Z. Yan {beta}-Amyloid Peptides Impair PKC-Dependent Functions of Metabotropic Glutamate Receptors in Prefrontal Cortical Neurons J Neurophysiol, June 1, 2005; 93(6): 3102 - 3111. [Abstract] [Full Text] [PDF]

				H. Tan, P. Zhong, and Z. Yan Corticotropin-Releasing Factor and Acute Stress Prolongs Serotonergic Regulation of GABA Transmission in Prefrontal Cortical Pyramidal Neurons J. Neurosci., May 26, 2004; 24(21): 5000 - 5008. [Abstract] [Full Text] [PDF]

				R. DeLong Autism and Familial Major Mood Disorder: Are They Related? J Neuropsychiatry Clin Neurosci, May 1, 2004; 16(2): 199 - 213. [Abstract] [Full Text] [PDF]

				G. Chen, P. Greengard, and Z. Yan Potentiation of NMDA receptor currents by dopamine D1 receptors in prefrontal cortex PNAS, February 24, 2004; 101(8): 2596 - 2600. [Abstract] [Full Text] [PDF]

				J. P. Tyszkiewicz, Z. Gu, X. Wang, X. Cai, and Z. Yan Group II metabotropic glutamate receptors enhance NMDA receptor currents via a protein kinase C-dependent mechanism in pyramidal neurones of rat prefrontal cortex J. Physiol., February 1, 2004; 554(3): 765 - 777. [Abstract] [Full Text] [PDF]

				J. N. Jovanovic, P. Thomas, J. T. Kittler, T. G. Smart, and S. J. Moss Brain-Derived Neurotrophic Factor Modulates Fast Synaptic Inhibition by Regulating GABAA Receptor Phosphorylation, Activity, and Cell-Surface Stability J. Neurosci., January 14, 2004; 24(2): 522 - 530. [Abstract] [Full Text] [PDF]

				X. Wang, P. Zhong, Z. Gu, and Z. Yan Regulation of NMDA Receptors by Dopamine D4 Signaling in Prefrontal Cortex J. Neurosci., October 29, 2003; 23(30): 9852 - 9861. [Abstract] [Full Text] [PDF]

				P. Zhong, Z. Gu, X. Wang, H. Jiang, J. Feng, and Z. Yan Impaired Modulation of GABAergic Transmission by Muscarinic Receptors in a Mouse Transgenic Model of Alzheimer's Disease J. Biol. Chem., July 11, 2003; 278(29): 26888 - 26896. [Abstract] [Full Text] [PDF]

				Z. Gu, P. Zhong, and Z. Yan Activation of Muscarinic Receptors Inhibits beta -Amyloid Peptide-induced Signaling in Cortical Slices J. Biol. Chem., May 2, 2003; 278(19): 17546 - 17556. [Abstract] [Full Text] [PDF]

				X.-H. Ma, P. Zhong, Z. Gu, J. Feng, and Z. Yan Muscarinic Potentiation of GABAA Receptor Currents Is Gated by Insulin Signaling in the Prefrontal Cortex J. Neurosci., February 15, 2003; 23(4): 1159 - 1168. [Abstract] [Full Text] [PDF]

				J.-J. Koksma, R. E. van Kesteren, T. W. Rosahl, R. Zwart, A. B. Smit, H. Luddens, and A. B. Brussaard Oxytocin Regulates Neurosteroid Modulation of GABAA Receptors in Supraoptic Nucleus around Parturition J. Neurosci., February 1, 2003; 23(3): 788 - 797. [Abstract] [Full Text] [PDF]

				K. R. Birikh, E. H. Sklan, S. Shoham, and H. Soreq Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCbeta II correlates with intensified fear-induced conflict behavior PNAS, January 7, 2003; 100(1): 283 - 288. [Abstract] [Full Text] [PDF]

				A. McCahill, J. Warwicker, G. B. Bolger, M. D. Houslay, and S. J. Yarwood The RACK1 Scaffold Protein: A Dynamic Cog in Cell Response Mechanisms Mol. Pharmacol., December 1, 2002; 62(6): 1261 - 1273. [Full Text] [PDF]

				X. Wang, P. Zhong, and Z. Yan Dopamine D4 Receptors Modulate GABAergic Signaling in Pyramidal Neurons of Prefrontal Cortex J. Neurosci., November 1, 2002; 22(21): 9185 - 9193. [Abstract] [Full Text] [PDF]

				X. Cai, Z. Gu, P. Zhong, Y. Ren, and Z. Yan Serotonin 5-HT1A Receptors Regulate AMPA Receptor Channels through Inhibiting Ca2+/Calmodulin-dependent Kinase II in Prefrontal Cortical Pyramidal Neurons J. Biol. Chem., September 20, 2002; 277(39): 36553 - 36562. [Abstract] [Full Text] [PDF]

				D. B. Carr, D. C. Cooper, S. L. Ulrich, N. Spruston, and D. J. Surmeier Serotonin Receptor Activation Inhibits Sodium Current and Dendritic Excitability in Prefrontal Cortex via a Protein Kinase C-Dependent Mechanism J. Neurosci., August 15, 2002; 22(16): 6846 - 6855. [Abstract] [Full Text] [PDF]

				N. J. Brandon, J. N. Jovanovic, T. G. Smart, and S. J. Moss Receptor for Activated C Kinase-1 Facilitates Protein Kinase C-Dependent Phosphorylation and Functional Modulation of GABAA Receptors with the Activation of G-Protein-Coupled Receptors J. Neurosci., August 1, 2002; 22(15): 6353 - 6361. [Abstract] [Full Text] [PDF]

				X. Cai, J. Flores-Hernandez, J. Feng, and Z. Yan Activity-dependent bidirectional regulation of GABAA receptor channels by the 5-HT4 receptor-mediated signalling in rat prefrontal cortical pyramidal neurons J. Physiol., May 1, 2002; 540(3): 743 - 759. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help