title: Activity-dependent long-term potentiation of intrinsic excitability in hippocampal CA1 pyramidal neurons.
abstract: The efficiency of neural circuits is enhanced not only by increasing synaptic strength but also by increasing intrinsic excitability. In contrast to the detailed analysis of long-term potentiation (LTP), less attention has been given to activity-dependent changes in the intrinsic neuronal excitability. By stimulating hippocampal CA1 pyramidal neurons with synaptic inputs correlating with postsynaptic neuronal spikes, we elicited an LTP of intrinsic excitability (LTP-IE) concurring with synaptic LTP. LTP-IE was manifested as a decrease in the action potential threshold that was attributable to a hyperpolarized shift in the activation curve of voltage-gated sodium channels (VGSCs) rather than activity-dependent changes in synaptic inputs or A-type K+ channels. Cell-attached patch recording of VGSC activities indicated such an activity-dependent change in VGSCs. Induction of LTP-IE was blocked by the NMDA receptor antagonist APV, intracellular BAPTA, the CaM kinase inhibitors KN-62 and autocamtide-2-related inhibitory peptide, and the protein synthesis inhibitors emetine and anisomycin. The results suggest that induction of LTP-IE shares a similar signaling pathway with the late phase of synaptic LTP and requires activation of the NMDA glutamate receptor subtype, Ca2+ influx, activity of CaM kinase II, and function of the protein synthesis. This new form of hippocampal neuronal plasticity could be a cellular correlate of learning and memory besides synaptic LTP.
authors.affiliation: Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007858:Learning / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010721:Phosphinic Acids; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010721:Phosphinic Acids; D015221:Potassium Channels; D011412:Propanolamines; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; C085075:CGP 55845A; D004533:Egtazic Acid; C063302:KN 62; D000841:Anisomycin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015761:4-Aminopyridine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D004640:Emetine; D001640:Bicuculline
references.citation: Nat Neurosci. 1998 Dec;1(8):683-92
references.pmid: 10196584
references.citation: Science. 1999 Sep 17;285(5435):1870-4
references.pmid: 10489359
references.citation: J Neurophysiol. 1999 Dec;82(6):2903-13
references.pmid: 10601428
references.citation: J Neurophysiol. 2000 Jan;83(1):70-80
references.pmid: 10634854
references.citation: Nat Neurosci. 2000 Feb;3(2):109-11
references.pmid: 10649564
references.citation: Nat Neurosci. 2000 Apr;3(4):330-6
references.pmid: 10725921
references.citation: Neuron. 2000 Apr;26(1):13-25
references.pmid: 10798388
references.citation: J Neurosci. 2000 Jul 15;20(14):5208-16
references.pmid: 10884304
references.citation: Nat Neurosci. 2000 Oct;3(10):1018-26
references.pmid: 11017175
references.citation: J Neurosci. 2001 Feb 15;21(4):1385-92
references.pmid: 11160410
references.citation: J Neurosci. 2001 Feb 15;21(4):1401-12
references.pmid: 11160412
references.citation: Neuron. 2001 May;30(2):503-13
references.pmid: 11395010
references.citation: J Neurosci. 2001 Aug 15;21(16):6413-22
references.pmid: 11487665
references.citation: Neuron. 2002 Jan 31;33(3):439-52
references.pmid: 11832230
references.citation: Neuron. 2002 Mar 28;34(1):107-14
references.pmid: 11931745
references.citation: J Neurophysiol. 2002 Jul;88(1):107-16
references.pmid: 12091536
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14512-7
references.pmid: 12391303
references.citation: Neuron. 2003 Feb 6;37(3):463-72
references.pmid: 12575953
references.citation: J Neurophysiol. 2003 Oct;90(4):2171-9
references.pmid: 12815013
references.citation: Neuron. 2003 Aug 28;39(5):831-42
references.pmid: 12948449
references.citation: J Neurosci. 1992 Feb;12(2):607-18
references.pmid: 1311034
references.citation: Nat Rev Neurosci. 2003 Nov;4(11):885-900
references.pmid: 14595400
references.citation: J Neurosci. 2003 Nov 12;23(32):10238-48
references.pmid: 14614082
references.citation: Hippocampus. 2003;13(7):801-5
references.pmid: 14620875
references.citation: Nat Neurosci. 2004 Feb;7(2):126-35
references.pmid: 14730307
references.citation: J Neurophysiol. 2004 Jul;92(1):341-8
references.pmid: 14973317
references.citation: Nat Neurosci. 2004 May;7(5):518-24
references.pmid: 15048122
references.citation: J Neurosci. 2004 May 12;24(19):4530-4
references.pmid: 15140923
references.citation: Methods Enzymol. 1992;207:123-31
references.pmid: 1528115
references.citation: Neuron. 1991 Jan;6(1):53-60
references.pmid: 1670922
references.citation: Exp Brain Res. 1990;79(3):633-41
references.pmid: 2340880
references.citation: Science. 1989 Aug 25;245(4920):862-6
references.pmid: 2549638
references.citation: J Physiol. 1987 Dec;394:367-80
references.pmid: 3443970
references.citation: Behav Neural Biol. 1985 Sep;44(2):278-300
references.pmid: 4062781
references.citation: J Physiol. 1973 Jul;232(2):331-56
references.pmid: 4727084
references.citation: Pflugers Arch. 1981 Aug;391(2):85-100
references.pmid: 6270629
references.citation: J Physiol. 1983 Jan;334:33-46
references.pmid: 6306230
references.citation: J Physiol. 1983 Mar;336:285-300
references.pmid: 6875910
references.citation: J Physiol. 1980 May;302:463-82
references.pmid: 7411464
references.citation: J Physiol. 1995 Aug 15;487(1):67-90
references.pmid: 7473260
references.citation: Trends Neurosci. 1993 Dec;16(12):521-7
references.pmid: 7509523
references.citation: J Physiol. 1995 May 1;484 ( Pt 3):689-705
references.pmid: 7623285
references.citation: Biochem Biophys Res Commun. 1995 Jul 26;212(3):806-12
references.pmid: 7626114
references.citation: Annu Rev Physiol. 1995;57:417-45
references.pmid: 7778873
references.citation: Neuroscience. 1994 Oct;62(4):1021-32
references.pmid: 7845583
references.citation: J Biol Chem. 1994 Jun 3;269(22):15520-7
references.pmid: 8195196
references.citation: Science. 1993 Jun 11;260(5114):1661-4
references.pmid: 8389057
references.citation: Nature. 1993 Jan 7;361(6407):31-9
references.pmid: 8421494
references.citation: Brain Res Brain Res Rev. 1993 Jan-Apr;18(1):115-22
references.pmid: 8467347
references.citation: J Biol Chem. 1996 Oct 4;271(40):24329-32
references.pmid: 8798683
references.citation: J Neurosci. 1996 Nov 1;16(21):6676-86
references.pmid: 8824308
references.citation: J Neurophysiol. 1996 Nov;76(5):3126-35
references.pmid: 8930260
references.citation: Science. 1997 Jan 10;275(5297):209-13
references.pmid: 8985013
references.citation: Science. 1997 Jan 10;275(5297):213-5
references.pmid: 8985014
references.citation: Cell. 1997 Mar 7;88(5):615-26
references.pmid: 9054501
references.citation: J Neurophysiol. 1997 Jan;77(1):86-92
references.pmid: 9120599
references.citation: Science. 1997 Jun 27;276(5321):2001-2
references.pmid: 9221509
references.citation: J Biol Chem. 1997 Aug 1;272(31):19103-6
references.pmid: 9235897
references.citation: J Physiol. 1998 Feb 15;507 ( Pt 1):237-47
references.pmid: 9490845
references.citation: J Neurosci. 1998 Jul 15;18(14):5498-507
references.pmid: 9651230
references.citation: J Neurosci. 1998 Aug 1;18(15):5988-98
references.pmid: 9671684
references.citation: Eur J Neurosci. 1998 Apr;10(4):1518-23
references.pmid: 9749805
references.citation: J Neurosci. 1998 Dec 15;18(24):10464-72
references.pmid: 9852584
references.citation: J Neurophysiol. 1999 Jan;81(1):277-87
references.pmid: 9914288