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The Journal of Neuroscience, 2001, 21:RC188:1-5
RAPID COMMUNICATION
Metabotropic Glutamate Receptors Drive the Endocannabinoid System
in Hippocampus
Namita
Varma1,
Gregory
C.
Carlson1,
Catherine
Ledent2, and
Bradley E.
Alger1
1 Department of Physiology and Program in Neuroscience,
University of Maryland School of Medicine, Baltimore, Maryland 21201, and 2 Institut de Recherche Interdisciplinaire en Biologie
Humaine et Nucléaire, Université libre de Bruxelles,
B-1070 Brussels, Belgium
Endocannabinoids are key intercellular signaling molecules in the
brain, but the physiological regulation of the endocannabinoid system
is not understood. We used the retrograde signal process called
depolarization-induced suppression of inhibition (DSI) to study the
regulation of this system. DSI is produced when an endocannabinoid
released from pyramidal cells suppresses IPSCs by activating
CB1R cannabinoid receptors located on inhibitory interneurons. We now
report that activation of group I metabotropic glutamate receptors
(mGluRs) enhances DSI and that this effect is blocked by antagonists of
both mGluRs and of CB1R. We also found that DSI is absent in CB1R
knock-out (CB1R / ) mice, and, strikingly, that
mGluR agonists have no effect on IPSCs in these mice. We conclude that
group I mGluR-induced enhancement of DSI, and suppression of IPSCs, is
actually mediated by endocannabinoids. This surprising result opens up
new approaches to the investigation of cannabinoid actions in the brain.
Key words:
DSI; IPSCs; retrograde; transmitter release; cannabinoid; CB1; mGluR; CA1; presynaptic; disinhibition
Copyright © Society for Neuroscience 0270-6474//$05.00/0
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|
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|
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|

|
 |

|
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|
 |
|

|
 |

|
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|
 |
|

|
 |

|
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[Full Text]
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|
 |
|

|
 |

|
 |
 
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[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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92(3):
1558 - 1565.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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310(3):
1152 - 1160.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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September 1, 2004;
559(2):
611 - 624.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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24(26):
5955 - 5965.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Harkany, C. Holmgren, W. Hartig, T. Qureshi, F. A. Chaudhry, J. Storm-Mathisen, M. B. Dobszay, P. Berghuis, G. Schulte, K. M. Sousa, et al.
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May 26, 2004;
24(21):
4978 - 4988.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Galante and M. A. Diana
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24(20):
4865 - 4874.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Losonczy, A. A. Biro, and Z. Nusser
Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons
PNAS,
February 3, 2004;
101(5):
1362 - 1367.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Melis, M. Pistis, S. Perra, A. L. Muntoni, G. Pillolla, and G. L. Gessa
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J. Neurosci.,
January 7, 2004;
24(1):
53 - 62.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Oz, A. Ravindran, O. Diaz-Ruiz, L. Zhang, and M. Morales
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306(3):
1003 - 1010.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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August 20, 2003;
23(20):
7659 - 7669.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. D. Brenowitz and W. G. Regehr
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J. Neurosci.,
July 16, 2003;
23(15):
6373 - 6384.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. F. FREUND, I. KATONA, and D. PIOMELLI
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Physiol Rev,
July 1, 2003;
83(3):
1017 - 1066.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Trettel and E. S. Levine
Endocannabinoids Mediate Rapid Retrograde Signaling At Interneuron right-arrow Pyramidal Neuron Synapses of the Neocortex
J Neurophysiol,
April 1, 2003;
89(4):
2334 - 2338.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Kim, M. Isokawa, C. Ledent, and B. E. Alger
Activation of Muscarinic Acetylcholine Receptors Enhances the Release of Endogenous Cannabinoids in the Hippocampus
J. Neurosci.,
December 1, 2002;
22(23):
10182 - 10191.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Robbe, M. Kopf, A. Remaury, J. Bockaert, and O. J. Manzoni
Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens
PNAS,
June 11, 2002;
99(12):
8384 - 8388.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Presynaptic Cannabinoid Sensitivity Is a Major Determinant of Depolarization-Induced Retrograde Suppression at Hippocampal Synapses
J. Neurosci.,
May 15, 2002;
22(10):
3864 - 3872.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|