title: Input-specific plasticity at excitatory synapses mediated by endocannabinoids in the dentate gyrus.
abstract: Endocannabinoids (eCBs) mediate transient and long-lasting synaptic plasticity in several brain structures. In the dentate gyrus, activation of the type 1 cannabinoid receptor (CB1R) by exogenous ligands reportedly depresses excitatory synaptic transmission. However, direct evidence of eCB signaling at excitatory synapses in this region has been lacking. Here, we demonstrate that eCB release can be induced by a brief postsynaptic depolarization of dentate granule cells (DGCs), which potently and transiently suppresses glutamatergic inputs from mossy cell interneurons (MCs) but not from entorhinal cortex via the lateral and medial perforant paths. This input-specific depolarization-induced suppression of excitation (DSE) is calcium-dependent and can be modulated by agonists of cholinergic and group I metabotropic glutamate receptors. Inhibiting the synthesis of 2-arachidonoyl glycerol (2-AG), one of the most abundant eCBs in the brain, by diacyglycerol lipase (DGL) does not abolish DSE. Moreover, preventing the breakdown of anandamide, the other main eCB, does not potentiate DSE. Thus, eCB signaling underlying DSE in the dentate does not require DGL activity and is unlikely to be mediated by anandamide. Finally, we find that manipulations known to induce eCB-LTD at other central synapses do not trigger LTD at MCF-DGC synapses.
authors: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Chiayu Q
authors: CQ
authors: Chiu
authors: Pablo E
authors: PE
authors: Castillo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism; D048588:Benzoxazines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D018678:Cholinergic Agents / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology*; D004558:Electric Stimulation; D063388:Endocannabinoids; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005989:Glycerides / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D002121:Calcium Channel Blockers; D063385:Cannabinoid Receptor Modulators; D018678:Cholinergic Agents; D063388:Endocannabinoids; D005989:Glycerides; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094503:glyceryl 2-arachidonate; D002118:Calcium
references: Br J Pharmacol. 2004 May;142(1):9-19
references: 15100161
references: J Neurophysiol. 1995 Jul;74(1):179-94
references: 7472322
references: Nat Neurosci. 2004 Jul;7(7):697-8
references: 15184902
references: Biochem Pharmacol. 2004 Nov 1;68(9):1691-8
references: 15450934
references: Neuron. 2004 Sep 30;44(1):5-21
references: 15450156
references: Brain Res. 1981 May 18;212(2):287-300
references: 7225870
references: J Comp Neurol. 1985 Sep 8;239(2):237-46
references: 4044938
references: Neuroscience. 1989;31(3):571-91
references: 2687721
references: Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932-6
references: 2308954
references: Cereb Cortex. 1993 Mar-Apr;3(2):133-47
references: 8490319
references: Hippocampus. 1992 Oct;2(4):349-62
references: 1284975
references: J Neurosci. 1994 May;14(5 Pt 2):3106-21
references: 8182460
references: Ann Neurol. 1994 Jun;35(6):640-54
references: 8210220
references: J Comp Neurol. 1996 Mar 4;366(2):271-92
references: 8698887
references: J Neurophysiol. 1996 Dec;76(6):3798-806
references: 8985877
references: J Comp Neurol. 1997 Apr 14;380(3):382-94
references: 9087520
references: J Neurosci. 1997 Oct 1;17(19):7503-22
references: 9295396
references: Neuroscience. 1998 Mar;83(2):393-411
references: 9460749
references: J Comp Neurol. 1998 Oct 26;400(3):391-407
references: 9779943
references: Proc Natl Acad Sci U S A. 1999 May 11;96(10):5780-5
references: 10318961
references: J Neurosci. 1999 Nov 1;19(21):9519-29
references: 10531454
references: J Neurosci. 2001 Dec 15;21(24):RC188
references: 11734603
references: Trends Neurosci. 2002 Mar;25(3):140-4
references: 11852145
references: Eur J Neurosci. 2002 Mar;15(6):953-61
references: 11918654
references: Curr Opin Neurobiol. 2002 Jun;12(3):324-30
references: 12049940
references: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8384-8
references: 12060781
references: Mol Neurobiol. 2002 Oct-Dec;26(2-3):317-46
references: 12428763
references: J Neurosci. 2002 Dec 1;22(23):10182-91
references: 12451119
references: Prog Neurobiol. 2002 Nov;68(4):247-86
references: 12498988
references: Nat Med. 2003 Jan;9(1):76-81
references: 12461523
references: Neuron. 2003 May 8;38(3):461-72
references: 12741992
references: Physiol Rev. 2003 Jul;83(3):1017-66
references: 12843414
references: Eur J Neurosci. 2003 Jul;18(1):109-16
references: 12859343
references: Neuron. 2003 Aug 14;39(4):599-611
references: 12925275
references: Neuron. 2003 Aug 14;39(4):641-54
references: 12925278
references: J Neurophysiol. 2003 Oct;90(4):2536-47
references: 14534276
references: Br J Pharmacol. 2003 Nov;140(5):781-9
references: 14504143
references: Nat Rev Neurosci. 2003 Nov;4(11):873-84
references: 14595399
references: J Cell Biol. 2003 Nov 10;163(3):463-8
references: 14610053
references: J Neurosci. 1999 Jun 1;19(11):4544-58
references: 10341254
references: Neuroscience. 1999;92(1):61-71
references: 10392830
references: J Neurosci. 2004 Nov 3;24(44):9953-61
references: 15525780
references: Nat Neurosci. 2005 Sep;8(9):1139-41
references: 16116451
references: J Physiol. 2005 Sep 15;567(Pt 3):1001-10
references: 16037085
references: J Neurosci. 2005 Nov 9;25(45):10537-45
references: 16280591
references: Neuron. 2005 Nov 23;48(4):647-59
references: 16301180
references: J Neurophysiol. 2006 Jan;95(1):67-75
references: 16207781
references: J Neurosci. 2006 Mar 15;26(11):2991-3001
references: 16540577
references: J Neurosci. 2006 Apr 19;26(16):4166-77
references: 16624937
references: Neuroscience. 2006;139(3):795-802
references: 16527424
references: J Neurosci. 2006 May 24;26(21):5628-37
references: 16723519
references: J Neurosci. 2006 May 24;26(21):5794-9
references: 16723537
references: J Endocrinol Invest. 2006;29(3 Suppl):3-14
references: 16751705
references: Annu Rev Neurosci. 2006;29:37-76
references: 16776579
references: Neuron. 2006 Aug 17;51(4):455-66
references: 16908411
references: J Physiol. 2006 Nov 15;577(Pt 1):263-80
references: 16973696
references: J Neurosci. 2007 Jan 31;27(5):1211-9
references: 17267577
references: J Neurosci. 2007 May 9;27(19):5260-4
references: 17494712
references: J Neurosci. 2004 May 19;24(20):4865-74
references: 15152047