title: Persistent receptor activity underlies group I mGluR-mediated cellular plasticity in CA3 neuron.
abstract: Plastic changes in cortical activities induced by group I metabotropic glutamate receptor (mGluR) stimulation include epileptogenesis, expressed in vitro as the conversion of normal neuronal activity to persistent, prolonged synchronized (ictal) discharges. At present, the mechanism that maintains group I mGluR-induced plasticity is not known. We examined this issue using hippocampal slices from guinea pigs and mice. Agonist [(S)-3,5-dihydroxyphenylglycine (DHPG), 30-50 μm)] stimulation of group I mGluRs induces persistent prolonged synchronized (ictal-like) discharges in CA3 that are associated with three identified excitatory cellular responses-suppression of spike afterhyperpolarizations, activation of a voltage-dependent cationic current, and increase in neuronal input resistance. Persistent prolonged synchronized discharges and the underlying excitatory cellular responses maintained following induction were reversibly blocked by mGluR1 antagonists [(S)-+-α-amino-4-carboxy-2-methylbenzeneacetic acid (LY 367385), 50, 100 μm; CPCCOEt (hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester, 100 μm], and to a lesser extent by the mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride, 50 μm]. Activation of persistent cellular responses to DHPG were unaffected by tetrodotoxin (0.5-1 μm) or perfusion with low Ca(2+)(0.2 mm)-Mn(2+)(0.5 mm) media-conditions that suppress endogenous glutamate release. The pharmacological profile of the blocking action of the group I mGluR antagonist MCPG [(RS)-α-methyl-4-carboxyphenylglycine, 50-500 μm] on persistent cellular responses was different from that on cellular responses directly activated by DHPG. These data indicate that transient stimulation of group I mGluRs alters receptor properties, rendering them persistently active in the absence of applied agonist or endogenous glutamate activation. Persistent receptor activities, primarily involving mGluR1, maintain excitatory cellular responses and emergent prolonged synchronized discharges.
authors: Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA.
authors: Steven R
authors: SR
authors: Young
authors: Shih-Chieh
authors: SC
authors: Chuang
authors: Wangfa
authors: W
authors: Zhao
authors: Robert K S
authors: RK
authors: Wong
authors: Riccardo
authors: R
authors: Bianchi
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D008734:Methoxyhydroxyphenylglycol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C010117:3,4-dihydroxyphenylglycol
references: Annu Rev Pharmacol Toxicol. 2010;50:295-322
references: 20055706
references: Neuron. 2004 Sep 2;43(5):729-43
references: 15339653
references: Trends Pharmacol Sci. 2002 Jun;23(6):268-74
references: 12084632
references: J Neurophysiol. 2002 Jan;87(1):621-5
references: 11784776
references: J Neurophysiol. 1997 Jul;78(1):539-44
references: 9242303
references: Nature. 2001 Jun 21;411(6840):962-5
references: 11418862
references: J Neurophysiol. 2003 Mar;89(3):1308-16
references: 12626613
references: J Physiol. 2004 Jan 15;554(Pt 2):371-85
references: 14578486
references: Mol Pharmacol. 2003 Oct;64(4):823-32
references: 14500738
references: Neuropharmacology. 2011 Jan;60(1):82-92
references: 20713070
references: Brain. 2009 Oct;132(Pt 10):2805-21
references: 19755519
references: Nat Neurosci. 2012 Jan 22;15(3):431-40, S1
references: 22267161
references: J Physiol. 1995 Sep 15;487 ( Pt 3):663-76
references: 8544129
references: Proc Natl Acad Sci U S A. 1989 Oct;86(19):7321-5
references: 2552439
references: FASEB J. 1987 Nov;1(5):365-74
references: 3315805
references: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2660-5
references: 11867751
references: Semin Cell Dev Biol. 2004 Jun;15(3):289-98
references: 15125892
references: J Neurosci. 2010 Nov 17;30(46):15616-27
references: 21084617
references: J Neurosci. 1997 May 15;17(10):3445-54
references: 9133370
references: Nat Neurosci. 2009 May;12(5):593-601
references: 19377472
references: J Neurosci. 2009 Mar 18;29(11):3497-507
references: 19295155
references: J Neurochem. 2006 Jan;96(1):179-94
references: 16277605
references: Biophys J. 1990 May;57(5):1085-90
references: 1692749
references: J Neurosci. 1995 Dec;15(12):8039-52
references: 8613741
references: Neuron. 2007 Dec 20;56(6):955-62
references: 18093519
references: Nature. 1997 Mar 20;386(6622):284-8
references: 9069287
references: Epilepsia. 2012 Jan;53(1):157-67
references: 22150629
references: Mol Pharmacol. 2007 Mar;71(3):638-43
references: 17167032
references: Sci STKE. 2006 Oct 10;2006(356):re12
references: 17033045
references: Adv Neurol. 1999;79:685-98
references: 10514855
references: J Neurosci. 2004 Jan 7;24(1):76-84
references: 14715940
references: J Neurophysiol. 2000 May;83(5):2844-53
references: 10805682
references: J Neurosci. 2005 Aug 31;25(35):8048-55
references: 16135762
references: J Neurosci. 2011 May 25;31(21):7637-47
references: 21613477
references: Neuropharmacology. 1997 Nov-Dec;36(11-12):1517-32
references: 9517422
references: Nat Rev Mol Cell Biol. 2009 Dec;10(12):819-30
references: 19935667
references: J Neurosci. 2006 Mar 8;26(10):2673-83
references: 16525046
references: Trends Neurosci. 2004 Jul;27(7):370-7
references: 15219735
references: Science. 2000 May 19;288(5469):1254-7
references: 10818003
references: Nature. 2000 Oct 26;407(6807):971-7
references: 11069170
references: Mol Pharmacol. 2003 Dec;64(6):1271-6
references: 14645655
references: Mol Pharmacol. 2009 Jul;76(1):201-7
references: 19398535
references: J Neurophysiol. 2008 Mar;99(3):1105-18
references: 18184892
references: J Biol Chem. 1967 Feb 25;242(4):665-71
references: 6017735
references: J Neurosci. 2011 Jan 12;31(2):725-34
references: 21228181
references: Seizure. 2001 Jan;10(1):60-3
references: 11181100
references: J Physiol. 2002 May 15;541(Pt 1):113-21
references: 12015424
references: J Neurosci. 2004 Jul 14;24(28):6352-61
references: 15254091
references: Epilepsia. 1999 Aug;40(8):1092-9
references: 10448821
references: Epilepsy Curr. 2002 May;2(3):81-85
references: 15309152
references: Neuropharmacology. 2010 Jul-Aug;59(1-2):86-92
references: 20385148
references: J Neurosci. 2001 Aug 15;21(16):6387-94
references: 11487662
references: J Biol Chem. 2003 Mar 7;278(10):8340-7
references: 12509432
references: Trends Pharmacol Sci. 2007 Aug;28(8):431-7
references: 17644194
references: J Neurophysiol. 1999 Jun;81(6):2903-13
references: 10368407