title: Short- and long-term plasticity in CA1 neurons from mice lacking h-channel auxiliary subunit TRIP8b.
abstract: Hyperpolarization-activated cyclic nucleotide-gated nonselective cation channels (HCN or h-channels) are important regulators of neuronal physiology contributing to passive membrane properties, such as resting membrane potential and input resistance (R(N)), and to intrinsic oscillatory activity and synaptic integration. The correct membrane targeting of h-channels is regulated in part by the auxiliary h-channel protein TRIP8b. The genetic deletion of TRIP8b results in a loss of functional h-channels, which affects the postsynaptic integrative properties of neurons. We investigated the impact of TRIP8b deletion on long-term potentiation (LTP) at the two major excitatory inputs to CA1 pyramidal neurons: Schaffer collateral (SC) and perforant path (PP). We found that SC LTP was not significantly different between neurons from wild-type and TRIP8b-knockout mice. There was, however, significantly more short-term potentiation in knockout neurons. We also found that the persistent increase in h-current (I(h)) that normally occurs after LTP induction was absent in knockout neurons. The lack of I(h) plasticity was not restricted to activity-dependent induction, because the depletion of intracellular calcium stores also failed to produce the expected increase in I(h). Interestingly, pairing of SC and PP inputs resulted in a form of LTP in knockout neurons that did not occur in wild-type neurons. These results suggest that the physiological impact of TRIP8b deletion is not restricted to the integrative properties of neurons but also includes both synaptic and intrinsic plasticity.
authors: Center for Learning and Memory, University of Texas at Austin, Austin, Texas;
authors: Darrin H
authors: DH
authors: Brager
authors: Alan S
authors: AS
authors: Lewis
authors: Dane M
authors: DM
authors: Chetkovich
authors: Daniel
authors: D
authors: Johnston
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000378:metabolism*; D017774:Long-Term Potentiation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019580:Perforant Pathway / Q000502:physiology; D000074401:Peroxins; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008565:Membrane Proteins; D000074401:Peroxins; C501732:Pex5l protein, mouse; D021122:Protein Subunits
keywords: Ih; Schaffer collateral; hippocampus; intrinsic plasticity; perforant path
references: J Neurophysiol. 2009 Oct;102(4):2288-302
references: 19675296
references: Curr Opin Neurobiol. 2000 Jun;10(3):358-64
references: 10851171
references: J Neurosci. 2012 Oct 17;32(42):14835-48
references: 23077068
references: Nature. 1993 Jan 7;361(6407):31-9
references: 8421494
references: Neuron. 2010 Dec 9;68(5):921-35
references: 21145005
references: Neuron. 2007 Dec 20;56(6):1076-89
references: 18093528
references: J Neurosci. 2004 Nov 24;24(47):10750-62
references: 15564593
references: J Neurosci. 2007 Apr 25;27(17):4697-706
references: 17460082
references: Neuron. 2009 Jun 25;62(6):802-13
references: 19555649
references: PLoS One. 2012;7(2):e32181
references: 22363812
references: J Neurosci. 2009 Sep 2;29(35):10979-88
references: 19726656
references: J Comp Neurol. 2004 Apr 5;471(3):241-76
references: 14991560
references: Nat Neurosci. 2005 Nov;8(11):1542-51
references: 16234810
references: J Neurosci. 2008 May 28;28(22):5846-60
references: 18509046
references: Neuron. 2007 Dec 6;56(5):866-79
references: 18054862
references: Nat Neurosci. 2011 Apr;14(4):478-86
references: 21358644
references: Nat Neurosci. 2002 Aug;5(8):767-74
references: 12118259
references: Cell. 2004 Nov 24;119(5):719-32
references: 15550252
references: Nat Neurosci. 2002 Nov;5(11):1185-93
references: 12389030
references: J Neurosci. 2011 May 18;31(20):7424-40
references: 21593326
references: Neuron. 2011 May 12;70(3):495-509
references: 21555075
references: Nat Neurosci. 1999 Sep;2(9):848
references: 10461231
references: J Neurosci. 2009 May 13;29(19):6250-65
references: 19439603
references: Neuron. 2012 Aug 9;75(3):503-16
references: 22884333
references: Neuroscience. 1989;31(3):571-91
references: 2687721
references: Nat Neurosci. 2004 Feb;7(2):126-35
references: 14730307
references: J Neurosci. 1998 Oct 1;18(19):7613-24
references: 9742133
references: J Comp Neurol. 1976 Jun 1;167(3):285-314
references: 1270625
references: Neuron. 2007 Dec 20;56(6):1061-75
references: 18093527
references: Neurobiol Dis. 2008 Oct;32(1):26-36
references: 18657617
references: Neuron. 2009 Jun 25;62(6):814-25
references: 19555650
references: J Neurosci. 2011 Mar 16;31(11):4074-86
references: 21411649
references: Learn Mem. 2003 Jul-Aug;10(4):247-52
references: 12888542
references: Cell Rep. 2012 Mar 29;1(3):225-33
references: 22662315
references: J Neurosci. 2007 Dec 19;27(51):13926-37
references: 18094230
references: Nature. 1983 Oct 20-26;305(5936):719-21
references: 6415483
references: Brain Res. 1993 Mar 19;606(1):87-91
references: 8462007
references: Neuron. 2009 Apr 16;62(1):102-11
references: 19376070