 |
 Previous Article | Next Article 
The Journal of Neuroscience, August 15, 1999, 19(16):6795-6805
Mechanism of Cannabinoid Effects on Long-Term Potentiation and
Depression in Hippocampal CA1 Neurons
Dinah L.
Misner and
Jane M.
Sullivan
Molecular Neurobiology Laboratory, The Salk Institute, La
Jolla, California 92037
Cannabinoids, the active constituents of marijuana, are known to
impair learning and memory. Receptors for cannabinoids are highly
expressed in the hippocampus, a brain region that is believed to play
an important role in certain forms of learning and memory. To
investigate the possible contribution of cannabinoid receptor-mediated deficits in hippocampal function to the learning and memory impairments produced by marijuana, we studied the effects of cannabinoid receptor activation on two models of learning and memory, long-term potentiation (LTP) and long-term depression (LTD), in hippocampal slices. Although LTP and LTD of CA1 field potentials were blocked by cannabinoid receptor activation in the presence of Mg2+, they
could be induced after Mg2+ was removed. Similarly,
LTP and LTD of whole-cell EPSCs were unimpaired in the presence
of cannabinoid receptor agonist when the postsynaptic membrane was
depolarized during the LTP or LTD induction protocol. Cannabinoid
receptor activation also reduced EPSCs and enhanced paired-pulse
facilitation, while having no effect on the amplitude of spontaneous
miniature EPSCs. Finally, as with cannabinoid receptor activation,
inhibition of LTP by adenosine receptor activation could be overcome by
removal of Mg2+ or depolarization of the
postsynaptic membrane during tetanus. Our results indicate that
cannabinoid receptor activation does not directly inhibit the molecular
mechanisms responsible for long-term synaptic plasticity but instead
impairs LTP and LTD by reducing presynaptic neurotransmitter release to
a level below that required to depolarize the postsynaptic membrane to
relieve Mg2+ blockade of NMDA receptors.
Key words:
cannabinoids; cannabinoid receptors; hippocampus; synaptic transmission; long-term potentiation; long-term depression; learning and memory
Copyright © 1999 Society for Neuroscience 0270-6474/99/19166795-11$05.00/0
This article has been cited by other articles:
|
|
|
|
 
S. C. Azad, J. Kurz, G. Marsicano, B. Lutz, W. Zieglgansberger, and G. Rammes
Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala
Learn. Mem.,
March 5, 2008;
15(3):
143 - 152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Speed and L. E. Dobrunz
Developmental Decrease in Short-Term Facilitation at Schaffer Collateral Synapses in Hippocampus Is mGluR1 Sensitive
J Neurophysiol,
February 1, 2008;
99(2):
799 - 813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bjarnadottir, D. L. Misner, S. Haverfield-Gross, S. Bruun, V. G. Helgason, H. Stefansson, A. Sigmundsson, D. R. Firth, B. Nielsen, R. Stefansdottir, et al.
Neuregulin1 (NRG1) Signaling through Fyn Modulates NMDA Receptor Phosphorylation: Differential Synaptic Function in NRG1+/- Knock-Outs Compared with Wild-Type Mice
J. Neurosci.,
April 25, 2007;
27(17):
4519 - 4529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.-Y. Deng and S. Lei
Long-Term Depression in Identified Stellate Neurons of Juvenile Rat Entorhinal Cortex
J Neurophysiol,
January 1, 2007;
97(1):
727 - 737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. F. Hoffman, M. Oz, R. Yang, A. H. Lichtman, and C. R. Lupica
Opposing actions of chronic {Delta}9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation
Learn. Mem.,
January 1, 2007;
14(1-2):
63 - 74.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. van Beugen, R. Y. Nagaraja, and C. Hansel
Climbing fiber-evoked endocannabinoid signaling heterosynaptically suppresses presynaptic cerebellar long-term potentiation.
J. Neurosci.,
August 9, 2006;
26(32):
8289 - 8294.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Domenici, S. C. Azad, G. Marsicano, A. Schierloh, C. T. Wotjak, H.-U. Dodt, W. Zieglgansberger, B. Lutz, and G. Rammes
Cannabinoid Receptor Type 1 Located on Presynaptic Terminals of Principal Neurons in the Forebrain Controls Glutamatergic Synaptic Transmission
J. Neurosci.,
May 24, 2006;
26(21):
5794 - 5799.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yamasaki, K. Hashimoto, and M. Kano
Miniature Synaptic Events Elicited by Presynaptic Ca2+ Rise Are Selectively Suppressed by Cannabinoid Receptor Activation in Cerebellar Purkinje Cells
J. Neurosci.,
January 4, 2006;
26(1):
86 - 95.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Antonelli, M. C. Tomasini, M. Tattoli, T. Cassano, S. Tanganelli, S. Finetti, E. Mazzoni, L. Trabace, L. Steardo, V. Cuomo, et al.
Prenatal Exposure to the CB1 Receptor Agonist WIN 55,212-2 Causes Learning Disruption Associated with Impaired Cortical NMDA Receptor Function and Emotional Reactivity Changes in Rat Offspring
Cereb Cortex,
December 1, 2005;
15(12):
2013 - 2020.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Lozovaya, N. Yatsenko, A. Beketov, T. Tsintsadze, and N. Burnashev
Glycine Receptors in CNS Neurons as a Target for Nonretrograde Action of Cannabinoids
J. Neurosci.,
August 17, 2005;
25(33):
7499 - 7506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. D. Nosyreva and K. M. Huber
Developmental Switch in Synaptic Mechanisms of Hippocampal Metabotropic Glutamate Receptor-Dependent Long-Term Depression
J. Neurosci.,
March 16, 2005;
25(11):
2992 - 3001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Bayatti, H. Hermann, B. Lutz, and C. Behl
Corticotropin-Releasing Hormone-Mediated Induction of Intracellular Signaling Pathways and Brain-Derived Neurotrophic Factor Expression Is Inhibited by the Activation of the Endocannabinoid System
Endocrinology,
March 1, 2005;
146(3):
1205 - 1213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Cristiani, N. D. Pukay-Martin, and R. A. Bornstein
Marijuana Use and Cognitive Function in HIV-Infected People
J Neuropsychiatry Clin Neurosci,
August 1, 2004;
16(3):
330 - 335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Lei, K. A. Pelkey, L. Topolnik, P. Congar, J.-C. Lacaille, and C. J. McBain
Depolarization-Induced Long-Term Depression at Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses
J. Neurosci.,
October 29, 2003;
23(30):
9786 - 9795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. L. Colgin, E. A. Kramar, C. M. Gall, and G. Lynch
Septal Modulation of Excitatory Transmission in Hippocampus
J Neurophysiol,
October 1, 2003;
90(4):
2358 - 2366.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. F. FREUND, I. KATONA, and D. PIOMELLI
Role of Endogenous Cannabinoids in Synaptic Signaling
Physiol Rev,
July 1, 2003;
83(3):
1017 - 1066.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Mereu, M. Fa, L. Ferraro, R. Cagiano, T. Antonelli, M. Tattoli, V. Ghiglieri, S. Tanganelli, G. L. Gessa, and V. Cuomo
Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release
PNAS,
April 15, 2003;
100(8):
4915 - 4920.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Derkinderen, E. Valjent, M. Toutant, J.-C. Corvol, H. Enslen, C. Ledent, J. Trzaskos, J. Caboche, and J.-A. Girault
Regulation of Extracellular Signal-Regulated Kinase by Cannabinoids in Hippocampus
J. Neurosci.,
March 15, 2003;
23(6):
2371 - 2382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Azad, M. Eder, G. Marsicano, B. Lutz, W. Zieglgansberger, and G. Rammes
Activation of the Cannabinoid Receptor Type 1 Decreases Glutamatergic and GABAergic Synaptic Transmission in the Lateral Amygdala of the Mouse
Learn. Mem.,
March 1, 2003;
10(2):
116 - 128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Howlett, F. Barth, T. I. Bonner, G. Cabral, P. Casellas, W. A. Devane, C. C. Felder, M. Herkenham, K. Mackie, B. R. Martin, et al.
International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Pharmacol. Rev.,
June 1, 2002;
54(2):
161 - 202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ohno-Shosaku, H. Tsubokawa, I. Mizushima, N. Yoneda, A. Zimmer, and M. Kano
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]
|
|
|
|
|
|
|
R. I. Wilson and R. A. Nicoll
Endocannabinoid Signaling in the Brain
Science,
April 26, 2002;
296(5568):
678 - 682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Straiker, C. R. Borden, and J. M. Sullivan
G-Protein alpha Subunit Isoforms Couple Differentially to Receptors that Mediate Presynaptic Inhibition at Rat Hippocampal Synapses
J. Neurosci.,
April 1, 2002;
22(7):
2460 - 2468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-C. Huang, S.-W. Lo, and K.-S. Hsu
Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons
J. Physiol.,
May 1, 2001;
532(3):
731 - 748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. F. Hoffman and C. R. Lupica
Direct Actions of Cannabinoids on Synaptic Transmission in the Nucleus Accumbens: A Comparison With Opioids
J Neurophysiol,
January 1, 2001;
85(1):
72 - 83.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Hampson and S. A. Deadwyler
Cannabinoids Reveal the Necessity of Hippocampal Neural Encoding for Short-Term Memory in Rats
J. Neurosci.,
December 1, 2000;
20(23):
8932 - 8942.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Hampson, J. Mu, and S. A. Deadwyler
Cannabinoid and Kappa Opioid Receptors Reduce Potassium K Current via Activation of Gs Proteins in Cultured Hippocampal Neurons
J Neurophysiol,
November 1, 2000;
84(5):
2356 - 2364.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. KITTLER, E. V. GRIGORENKO, C. CLAYTON, S.-Y. ZHUANG, S. C. BUNDEY, M. M. TROWER, D. WALLACE, R. HAMPSON, and S. DEADWYLER
Large-scale analysis of gene expression changes during acute and chronic exposure to {Delta}9-THC in rats
Physiol Genomics,
September 8, 2000;
3(3):
175 - 185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Sullivan
Cellular and Molecular Mechanisms Underlying Learning and Memory Impairments Produced by Cannabinoids
Learn. Mem.,
May 1, 2000;
7(3):
132 - 139.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. F. Hoffman and C. R. Lupica
Mechanisms of Cannabinoid Inhibition of GABAA Synaptic Transmission in the Hippocampus
J. Neurosci.,
April 1, 2000;
20(7):
2470 - 2479.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Sullivan
Mechanisms of Cannabinoid-Receptor-Mediated Inhibition of Synaptic Transmission in Cultured Hippocampal Pyramidal Neurons
J Neurophysiol,
September 1, 1999;
82(3):
1286 - 1294.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Derkinderen, M. Toutant, G. Kadare, C. Ledent, M. Parmentier, and J.-A. Girault
Dual Role of Fyn in the Regulation of FAK+6,7 by Cannabinoids in Hippocampus
J. Biol. Chem.,
October 5, 2001;
276(41):
38289 - 38296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Kim and S. A. Thayer
Cannabinoids Inhibit the Formation of New Synapses between Hippocampal Neurons in Culture
J. Neurosci.,
May 15, 2001;
21(10):
RC146 - RC146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
