GABAB receptors modulate NMDA receptor calcium signals in dendritic spines.
Metabotropic GABA(B) receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABA(B) receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABA(B) receptors strongly inhibit NMDA receptor calcium signals. This postsynaptic modulation occurs via the PKA pathway and does not affect synaptic currents mediated by AMPA or NMDA receptors. This form of GABA(B) receptor modulation has widespread implications for the control of calcium-dependent neuronal function.
Chalifoux
Jason R
JR
Center for Neural Science, New York University, New York, NY 10003, USA.
Carter
Adam G
AG
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D051379:Mice; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology*; D018080:Receptors, GABA-B / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D055366:Synaptic Potentials / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D017868:Cyclic AMP-Dependent Protein Kinases
Nature. 1999 May 13;399(6732):151-5
10335844
Neuron. 1994 Jan;12(1):97-107
8292363
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14859-64
9405704
Science. 1999 Mar 19;283(5409):1923-7
10082466
Proc Natl Acad Sci U S A. 1985 Mar;82(5):1558-62
2983351
Neuron. 1996 Apr;16(4):825-33
8608000
Mol Neurobiol. 1996 Aug;13(1):23-32
8892334
Nat Neurosci. 2001 Nov;4(11):1086-92
11687814
Curr Opin Neurobiol. 1997 Jun;7(3):419-29
9232807
Nature. 2000 Nov 30;408(6812):589-93
11117746
Science. 2000 Oct 27;290(5492):750-4
11052931
Curr Opin Neurobiol. 1999 Jun;9(3):305-13
10395573
Curr Opin Neurobiol. 1995 Jun;5(3):268-77
7580148
Neuron. 1992 Nov;9(5):919-27
1358131
Neuron. 1993 Feb;10(2):165-75
7679913
Neuron. 2007 Jan 18;53(2):249-60
17224406
J Neurosci. 1998 May 1;18(9):3138-46
9547222
J Comp Neurol. 1991 Apr 8;306(2):332-43
1711059
Prog Neurobiol. 1991;36(1):35-92
1847747
Nature. 1999 May 6;399(6731):66-70
10331391
Neuron. 1997 Sep;19(3):687-95
9331358
J Neurosci. 1997 Dec 1;17(23):9048-59
9364051
Nat Neurosci. 2002 Jul;5(7):657-64
12055631
J Neurophysiol. 2004 Oct;92(4):2027-39
15163674
J Physiol. 1991 Dec;444:669-86
1668352
Eur J Neurosci. 1990;2(4):296-303
12106036
J Biol Chem. 1997 May 2;272(18):12107-15
9115280
J Neurosci. 2007 Aug 15;27(33):8967-77
17699678
Nature. 1988 Mar 10;332(6160):156-8
2831457
Nat Neurosci. 2009 Sep;12(9):1121-8
19668198
Neuron. 2001 Oct 25;32(2):301-13
11683999
Neuron. 1996 Feb;16(2):415-21
8789956
J Neurosci. 1991 Jan;11(1):203-9
1846009
J Neurosci. 2006 Apr 19;26(16):4289-97
16624949
J Physiol. 1985 Mar;360:161-85
3989713
J Physiol. 1984 Mar;348:239-54
6716285
Nature. 1994 May 19;369(6477):230-2
8183343
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4363-7
1350090
Pharmacol Rev. 2002 Jun;54(2):247-64
12037141
Nature. 1998 Dec 17;396(6712):683-7
9872317
Science. 1999 Jul 2;285(5424):93-6
10390370
Sci STKE. 2004 Feb 03;2004(219):pl5
14872098
J Neurosci. 2000 Mar 1;20(5):1791-9
10684880
J Neurosci. 2007 Aug 22;27(34):8999-9008
17715337
J Neurosci. 1996 Mar 1;16(5):1623-33
8774431
Annu Rev Neurosci. 1994;17:31-108
8210177
Neuron. 1993 Jul;11(1):133-43
7687849
J Neurosci. 1996 Oct 15;16(20):6374-85
8815916
Neuron. 2007 Jan 4;53(1):17-24
17196527
Curr Opin Neurobiol. 2003 Jun;13(3):366-71
12850222
Int Rev Neurobiol. 1994;36:97-223
7822122
Curr Opin Neurobiol. 1998 Jun;8(3):345-50
9687348
Physiol Rev. 2004 Jul;84(3):835-67
15269338
Neuron. 2004 Oct 28;44(3):483-93
15504328
J Physiol. 1995 Jun 15;485 ( Pt 3):649-57
7562607
Neuron. 2006 May 18;50(4):603-16
16701210
Neuron. 2006 May 18;50(4):589-601
16701209
J Biol Chem. 1997 Feb 21;272(8):5157-66
9030583
J Neurophysiol. 1984 Nov;52(5):892-910
6096520
Neuron. 2002 Dec 19;36(6):1115-26
12495626
Nature. 2003 Aug 14;424(6950):775-8
12917685
Neuron. 1998 Jul;21(1):13-26
9697848
J Physiol. 1994 Apr 15;476(2):203-15
7913968
Nat Neurosci. 2006 Apr;9(4):501-10
16531999
J Physiol. 1996 Mar 15;491 ( Pt 3):757-72
8815209
J Physiol. 1983 Jan;334:33-46
6306230
Neuron. 1993 May;10(5):889-98
8388225
Prog Neurobiol. 1995 Jul;46(4):423-62
8532848