 |
 Previous Article | Next Article 
The Journal of Neuroscience, December 1, 2002, 22(23):10182-10191
Activation of Muscarinic Acetylcholine Receptors Enhances the
Release of Endogenous Cannabinoids in the Hippocampus
Jimok
Kim1, 2,
Masako
Isokawa1, 2,
Catherine
Ledent3, and
Bradley E.
Alger1, 2
1 Program in Neuroscience and 2 Department
of Physiology, University of Maryland School of Medicine, Baltimore,
Maryland 21201, and 3 Institut de Recherche
Interdisciplinaire en Biologie Humaine et Nucléaire,
Université Libre de Bruxelles, B-1070 Brussels, Belgium
Endogenous cannabinoids (endocannabinoids) are endogenous compounds
that resemble the active ingredient of marijuana and activate the
cannabinoid receptor in the brain. They mediate retrograde signaling
from principal cells to both inhibitory ["depolarization-induced suppression of inhibition" (DSI)] and excitatory
("depolarization-induced suppression of excitation") afferent
fibers. Transient endocannabinoid release is triggered by
voltage-dependent Ca2+ influx and is upregulated by
group I metabotropic glutamate receptor activation. Here we show that
muscarinic acetylcholine receptor (mAChR) activation also enhances
transient endocannabinoid release (DSI) and induces persistent release.
Inhibitory synapses in the rat hippocampal CA1 region of acute slices
were studied using whole-cell patch-clamp techniques. We found that low
concentrations (0.2-0.5 µM) of carbachol (CCh) enhanced
DSI without affecting basal evoked IPSCs (eIPSCs) by activating mAChRs
on postsynaptic cells. Higher concentrations of CCh ( 1
µM) enhanced DSI and also persistently depressed basal
eIPSCs, mainly by releasing endocannabinoids. Persistent CCh-induced
endocannabinoid release did not require an increase in
[Ca2+]i but was dependent on
G-proteins. Although they were independent at the receptor level,
muscarinic and glutamatergic mechanisms of endocannabinoid release
shared intracellular machinery. Replication of the effects of CCh by
blocking acetylcholinesterase with eserine suggests that mAChR-mediated
endocannabinoid release is physiologically relevant. This study reveals
a new role of the muscarinic cholinergic system in mammalian brain.
Key words:
GABAergic IPSC; mAChR; DSI; retrograde messenger; retrograde signaling; mGluR
Copyright © 2002 Society for Neuroscience 0270-6474/02/222310182-10$05.00/0
This article has been cited by other articles:
|
|
|
|
 
Y.-J. Won, H. L. Puhl III, and S. R. Ikeda
Molecular Reconstruction of mGluR5a-Mediated Endocannabinoid Signaling Cascade in Single Rat Sympathetic Neurons
J. Neurosci.,
October 28, 2009;
29(43):
13603 - 13612.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Turu, P. Varnai, P. Gyombolai, L. Szidonya, L. Offertaler, G. Bagdy, G. Kunos, and L. Hunyady
Paracrine Transactivation of the CB1 Cannabinoid Receptor by AT1 Angiotensin and Other Gq/11 Protein-coupled Receptors
J. Biol. Chem.,
June 19, 2009;
284(25):
16914 - 16921.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kano, T. Ohno-Shosaku, Y. Hashimotodani, M. Uchigashima, and M. Watanabe
Endocannabinoid-Mediated Control of Synaptic Transmission
Physiol Rev,
January 1, 2009;
89(1):
309 - 380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Marinelli, S. Pacioni, T. Bisogno, V. Di Marzo, D. A. Prince, J. R. Huguenard, and A. Bacci
The Endocannabinoid 2-Arachidonoylglycerol Is Responsible for the Slow Self-Inhibition in Neocortical Interneurons
J. Neurosci.,
December 10, 2008;
28(50):
13532 - 13541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K. Lau and C. W. Vaughan
Muscarinic Modulation of Synaptic Transmission via Endocannabinoid Signalling in the Rat Midbrain Periaqueductal Gray
Mol. Pharmacol.,
November 1, 2008;
74(5):
1392 - 1398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Galarreta, F. Erdelyi, G. Szabo, and S. Hestrin
Cannabinoid Sensitivity and Synaptic Properties of 2 GABAergic Networks in the Neocortex
Cereb Cortex,
October 1, 2008;
18(10):
2296 - 2305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sheinin, G. Talani, M. I. Davis, and D. M. Lovinger
Endocannabinoid- and mGluR5-Dependent Short-Term Synaptic Depression in an Isolated Neuron/Bouton Preparation From the Hippocampal CA1 Region
J Neurophysiol,
August 1, 2008;
100(2):
1041 - 1052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Best and W. G. Regehr
Serotonin Evokes Endocannabinoid Release and Retrogradely Suppresses Excitatory Synapses
J. Neurosci.,
June 18, 2008;
28(25):
6508 - 6515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Edwards, L. Zhang, and B. E. Alger
Metaplastic control of the endocannabinoid system at inhibitory synapses in hippocampus
PNAS,
June 10, 2008;
105(23):
8142 - 8147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kyriakatos and A. El Manira
Long-Term Plasticity of the Spinal Locomotor Circuitry Mediated by Endocannabinoid and Nitric Oxide Signaling
J. Neurosci.,
November 14, 2007;
27(46):
12664 - 12674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Remy and N. Spruston
Dendritic spikes induce single-burst long-term potentiation
PNAS,
October 23, 2007;
104(43):
17192 - 17197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Hashimotodani, T. Ohno-Shosaku, M. Watanabe, and M. Kano
Roles of phospholipase Cbeta and NMDA receptor in activity-dependent endocannabinoid release
J. Physiol.,
October 15, 2007;
584(2):
373 - 380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. K. Makara, I. Katona, G. Nyiri, B. Nemeth, C. Ledent, M. Watanabe, J. de Vente, T. F. Freund, and N. Hajos
Involvement of Nitric Oxide in Depolarization-Induced Suppression of Inhibition in Hippocampal Pyramidal Cells during Activation of Cholinergic Receptors
J. Neurosci.,
September 19, 2007;
27(38):
10211 - 10222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Henneberger, S. J. Redman, and R. Grantyn
Cortical Efferent Control of Subcortical Sensory Neurons by Synaptic Disinhibition
Cereb Cortex,
September 1, 2007;
17(9):
2039 - 2049.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Uchigashima, M. Narushima, M. Fukaya, I. Katona, M. Kano, and M. Watanabe
Subcellular Arrangement of Molecules for 2-Arachidonoyl-Glycerol-Mediated Retrograde Signaling and Its Physiological Contribution to Synaptic Modulation in the Striatum
J. Neurosci.,
April 4, 2007;
27(14):
3663 - 3676.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Hashimotodani, T. Ohno-Shosaku, and M. Kano
Endocannabinoids and Synaptic Function in the CNS
Neuroscientist,
April 1, 2007;
13(2):
127 - 137.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Straiker and K. Mackie
Metabotropic suppression of excitation in murine autaptic hippocampal neurons
J. Physiol.,
February 1, 2007;
578(3):
773 - 785.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Narushima, M. Uchigashima, M. Fukaya, M. Matsui, T. Manabe, K. Hashimoto, M. Watanabe, and M. Kano
Tonic Enhancement of Endocannabinoid-Mediated Retrograde Suppression of Inhibition by Cholinergic Interneuron Activity in the Striatum
J. Neurosci.,
January 17, 2007;
27(3):
496 - 506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Chen, A. Neu, A. L. Howard, C. Foldy, J. Echegoyen, L. Hilgenberg, M. Smith, K. Mackie, and I. Soltesz
Prevention of Plasticity of Endocannabinoid Signaling Inhibits Persistent Limbic Hyperexcitability Caused by Developmental Seizures
J. Neurosci.,
January 3, 2007;
27(1):
46 - 58.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Fortin and E. S. Levine
Differential Effects of Endocannabinoids on Glutamatergic and GABAergic Inputs to Layer 5 Pyramidal Neurons
Cereb Cortex,
January 1, 2007;
17(1):
163 - 174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Neu, C. Foldy, and I. Soltesz
Postsynaptic origin of CB1-dependent tonic inhibition of GABA release at cholecystokinin-positive basket cell to pyramidal cell synapses in the CA1 region of the rat hippocampus
J. Physiol.,
January 1, 2007;
578(1):
233 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Szabo, M. J. Urbanski, T. Bisogno, V. D. Marzo, A. Mendiguren, W. U. Baer, and I. Freiman
Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol
J. Physiol.,
November 15, 2006;
577(1):
263 - 280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Hofmann, B. Nahir, and C. J. Frazier
Endocannabinoid-Mediated Depolarization-Induced Suppression of Inhibition in Hilar Mossy Cells of the Rat Dentate Gyrus
J Neurophysiol,
November 1, 2006;
96(5):
2501 - 2512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Pacher, S. Batkai, and G. Kunos
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pharmacol. Rev.,
September 1, 2006;
58(3):
389 - 462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Wettschureck, M. van der Stelt, H. Tsubokawa, H. Krestel, A. Moers, S. Petrosino, G. Schutz, V. Di Marzo, and S. Offermanns
Forebrain-Specific Inactivation of Gq/G11 Family G Proteins Results in Age-Dependent Epilepsy and Impaired Endocannabinoid Formation
Mol. Cell. Biol.,
August 1, 2006;
26(15):
5888 - 5894.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yoshida, M. Fukaya, M. Uchigashima, E. Miura, H. Kamiya, M. Kano, and M. Watanabe
Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor.
J. Neurosci.,
May 3, 2006;
26(18):
4740 - 4751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Edwards, J. Kim, and B. E. Alger
Multiple Mechanisms of Endocannabinoid Response Initiation in Hippocampus
J Neurophysiol,
January 1, 2006;
95(1):
67 - 75.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Di, C. Boudaba, I. R. Popescu, F.-J. Weng, C. Harris, V. L. Marcheselli, N. G. Bazan, and J. G. Tasker
Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus
J. Physiol.,
December 15, 2005;
569(3):
751 - 760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. G. Reich, M. A. Karson, S. V. Karnup, L. M. Jones, and B. E. Alger
Regulation of IPSP Theta Rhythm by Muscarinic Receptors and Endocannabinoids in Hippocampus
J Neurophysiol,
December 1, 2005;
94(6):
4290 - 4299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Thompson, J. P. Y. Kao, R. H. Kramer, K. E. Poskanzer, R. A. Silver, D. Digregorio, and S. S.-H. Wang
Flashy Science: Controlling Neural Function with Light
J. Neurosci.,
November 9, 2005;
25(45):
10358 - 10365.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. E. Alger
Endocannabinoid Identification in the Brain: Studies of Breakdown Lead to Breakthrough, and There May Be NO Hope
Sci. Signal.,
November 8, 2005;
2005(309):
pe51 - pe51.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-M. Jung, R. Mangieri, C. Stapleton, J. Kim, D. Fegley, M. Wallace, K. Mackie, and D. Piomelli
Stimulation of Endocannabinoid Formation in Brain Slice Cultures through Activation of Group I Metabotropic Glutamate Receptors
Mol. Pharmacol.,
November 1, 2005;
68(5):
1196 - 1202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Heinbockel, D. H. Brager, C. G. Reich, J. Zhao, S. Muralidharan, B. E. Alger, and J. P. Y. Kao
Endocannabinoid Signaling Dynamics Probed with Optical Tools
J. Neurosci.,
October 12, 2005;
25(41):
9449 - 9459.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Maejima, S. Oka, Y. Hashimotodani, T. Ohno-Shosaku, A. Aiba, D. Wu, K. Waku, T. Sugiura, and M. Kano
Synaptically Driven Endocannabinoid Release Requires Ca2+-Assisted Metabotropic Glutamate Receptor Subtype 1 to Phospholipase C {beta}4 Signaling Cascade in the Cerebellum
J. Neurosci.,
July 20, 2005;
25(29):
6826 - 6835.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Bodor, I. Katona, G. Nyiri, K. Mackie, C. Ledent, N. Hajos, and T. F. Freund
Endocannabinoid Signaling in Rat Somatosensory Cortex: Laminar Differences and Involvement of Specific Interneuron Types
J. Neurosci.,
July 20, 2005;
25(29):
6845 - 6856.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Haj-Dahmane and R.-Y. Shen
The Wake-Promoting Peptide Orexin-B Inhibits Glutamatergic Transmission to Dorsal Raphe Nucleus Serotonin Neurons through Retrograde Endocannabinoid Signaling
J. Neurosci.,
January 26, 2005;
25(4):
896 - 905.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. RODRIGUEZ de FONSECA, I. DEL ARCO, F. J. BERMUDEZ-SILVA, A. BILBAO, A. CIPPITELLI, and M. NAVARRO
THE ENDOCANNABINOID SYSTEM: PHYSIOLOGY AND PHARMACOLOGY
Alcohol Alcohol.,
January 1, 2005;
40(1):
2 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Fortin, J. Trettel, and E. S. Levine
Brief Trains of Action Potentials Enhance Pyramidal Neuron Excitability Via Endocannabinoid-Mediated Suppression of Inhibition
J Neurophysiol,
October 1, 2004;
92(4):
2105 - 2112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Galante and M. A. Diana
Group I Metabotropic Glutamate Receptors Inhibit GABA Release at Interneuron-Purkinje Cell Synapses through Endocannabinoid Production
J. Neurosci.,
May 19, 2004;
24(20):
4865 - 4874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Trettel, D. A. Fortin, and E. S. Levine
Endocannabinoid signalling selectively targets perisomatic inhibitory inputs to pyramidal neurones in juvenile mouse neocortex
J. Physiol.,
April 1, 2004;
556(1):
95 - 107.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
S. D. Brenowitz and W. G. Regehr
Calcium Dependence of Retrograde Inhibition by Endocannabinoids at Synapses onto Purkinje Cells
J. Neurosci.,
July 16, 2003;
23(15):
6373 - 6384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Hampson, S.-y. Zhuang, J. L. Weiner, and S. A. Deadwyler
Functional Significance of Cannabinoid-Mediated, Depolarization-Induced Suppression of Inhibition (DSI) in the Hippocampus
J Neurophysiol,
July 1, 2003;
90(1):
55 - 64.
[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]
|
|
|
|
|
