QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 15, 2006, 26(11):2991-3001; doi:10.1523/JNEUROSCI.4872-05.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (70) Citing Articles via Google Scholar Google Scholar Articles by Kawamura, Y. Articles by Kano, M. Search for Related Content PubMed PubMed Citation Articles by Kawamura, Y. Articles by Kano, M.

 Previous Article  |  Next Article 

Cellular/Molecular
The CB1 Cannabinoid Receptor Is the Major Cannabinoid Receptor at Excitatory Presynaptic Sites in the Hippocampus and Cerebellum

Yoshinobu Kawamura,^1 * Masahiro Fukaya,^2 * Takashi Maejima,³ Takayuki Yoshida,¹ Eriko Miura,² Masahiko Watanabe,² Takako Ohno-Shosaku,⁴ and Masanobu Kano¹

¹Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan, ²Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, ³Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan, and ⁴Department of Impairment Study, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0942, Japan

Correspondence should be addressed to Masanobu Kano, Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan. Email: mkano{at}cns.med.osaka-u.ac.jp

Endocannabinoids work as retrograde messengers and contribute to short-term and long-term modulation of synaptic transmission via presynaptic cannabinoid receptors. It is generally accepted that the CB1 cannabinoid receptor (CB1) mediates the effects of endocannabinoid in inhibitory synapses. For excitatory synapses, however, contributions of CB1, "CB3," and some other unidentified receptors have been suggested. In the present study we used electrophysiological and immunohistochemical techniques and examined the type(s) of cannabinoid receptor functioning at hippocampal and cerebellar excitatory synapses. Our electrophysiological data clearly demonstrate the predominant contribution of CB1. At hippocampal excitatory synapses on pyramidal neurons the cannabinoid-induced synaptic suppression was reversed by a CB1-specific antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), and was absent in CB1 knock-out mice. At climbing fiber (CF) and parallel fiber (PF) synapses on cerebellar Purkinje cells the cannabinoid-dependent suppression was absent in CB1 knock-out mice. The presence of CB1 at presynaptic terminals was confirmed by immunohistochemical experiments with specific antibodies against CB1. In immunoelectron microscopy the densities of CB1-positive signals in hippocampal excitatory terminals and cerebellar PF terminals were much lower than in inhibitory terminals but were clearly higher than the background. Along the long axis of PFs, the CB1 was localized at a much higher density on the perisynaptic membrane than on the extrasynaptic and synaptic regions. In contrast, CB1 density was low in CF terminals and was not significantly higher than the background. Despite the discrepancy between the electrophysiological and morphological data for CB1 expression on CFs, these results collectively indicate that CB1 is responsible for cannabinoid-dependent suppression of excitatory transmission in the hippocampus and cerebellum.

Key words: cannabinoid; CB1 receptor; presynaptic suppression; excitatory synapse; pyramidal cell; Purkinje cell; hippocampus; cerebellum

---

Received Nov. 12, 2005; revised Feb. 4, 2006; accepted Feb. 4, 2006.

Correspondence should be addressed to Masanobu Kano, Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan. Email: mkano{at}cns.med.osaka-u.ac.jp

This article has been cited by other articles:

				Y. M. Morozov, M. Torii, and P. Rakic Origin, Early Commitment, Migratory Routes, and Destination of Cannabinoid Type 1 Receptor-Containing Interneurons Cereb Cortex, July 1, 2009; 19(suppl_1): i78 - i89. [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]

				Y. Huang, H. Yasuda, A. Sarihi, and T. Tsumoto Roles of Endocannabinoids in Heterosynaptic Long-Term Depression of Excitatory Synaptic Transmission in Visual Cortex of Young Mice J. Neurosci., July 9, 2008; 28(28): 7074 - 7083. [Abstract] [Full Text] [PDF]

				S. M. Eggan, T. Hashimoto, and D. A. Lewis Reduced Cortical Cannabinoid 1 Receptor Messenger RNA and Protein Expression in Schizophrenia Arch Gen Psychiatry, July 1, 2008; 65(7): 772 - 784. [Abstract] [Full Text] [PDF]

				J. Mulder, T. Aguado, E. Keimpema, K. Barabas, C. J. Ballester Rosado, L. Nguyen, K. Monory, G. Marsicano, V. Di Marzo, Y. L. Hurd, et al. Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning PNAS, June 24, 2008; 105(25): 8760 - 8765. [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]

				S. J. Kim, Y. Jin, J. Kim, J. H. Shin, P. F. Worley, and D. J. Linden Transient Upregulation of Postsynaptic IP3-Gated Ca Release Underlies Short-Term Potentiation of Metabotropic Glutamate Receptor 1 Signaling in Cerebellar Purkinje Cells J. Neurosci., April 23, 2008; 28(17): 4350 - 4355. [Abstract] [Full Text] [PDF]

				A. Ludanyi, L. Eross, S. Czirjak, J. Vajda, P. Halasz, M. Watanabe, M. Palkovits, Z. Magloczky, T. F. Freund, and I. Katona Downregulation of the CB1 Cannabinoid Receptor and Related Molecular Elements of the Endocannabinoid System in Epileptic Human Hippocampus J. Neurosci., March 19, 2008; 28(12): 2976 - 2990. [Abstract] [Full Text] [PDF]

				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. Yasuda, Y. Huang, and T. Tsumoto Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus PNAS, February 26, 2008; 105(8): 3106 - 3111. [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]

				T. Ohno-Shosaku, Y. Hashimotodani, M. Ano, S. Takeda, H. Tsubokawa, and M. Kano Endocannabinoid signalling triggered by NMDA receptor-mediated calcium entry into rat hippocampal neurons J. Physiol., October 15, 2007; 584(2): 407 - 418. [Abstract] [Full Text] [PDF]

				M.-H. Kang-Park, W. A. Wilson, C. M. Kuhn, S. D. Moore, and H. S. Swartzwelder Differential Sensitivity of GABAA Receptor-Mediated IPSCs to Cannabinoids in Hippocampal Slices From Adolescent and Adult Rats J Neurophysiol, September 1, 2007; 98(3): 1223 - 1230. [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]

				E. L. Hill, T. Gallopin, I. Ferezou, B. Cauli, J. Rossier, P. Schweitzer, and B. Lambolez Functional CB1 Receptors Are Broadly Expressed in Neocortical GABAergic and Glutamatergic Neurons J Neurophysiol, April 1, 2007; 97(4): 2580 - 2589. [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]

				F. Crepel Developmental Changes in Retrograde Messengers Involved in Depolarization-Induced Suppression of Excitation at Parallel Fiber-Purkinje Cell Synapses in Rodents J Neurophysiol, January 1, 2007; 97(1): 824 - 836. [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. 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]

				Y. Kishimoto and M. Kano Endogenous Cannabinoid Signaling through the CB1 Receptor Is Essential for Cerebellum-Dependent Discrete Motor Learning. J. Neurosci., August 23, 2006; 26(34): 8829 - 8837. [Abstract] [Full Text] [PDF]

				I. Katona, G. M. Urban, M. Wallace, C. Ledent, K.-M. Jung, D. Piomelli, K. Mackie, and T. F. Freund Molecular Composition of the Endocannabinoid System at Glutamatergic Synapses J. Neurosci., May 24, 2006; 26(21): 5628 - 5637. [Abstract] [Full Text] [PDF]

				R. Tonini, S. Ciardo, M. Cerovic, T. Rubino, D. Parolaro, M. Mazzanti, and R. Zippel ERK-Dependent Modulation of Cerebellar Synaptic Plasticity after Chronic {Delta}9-Tetrahydrocannabinol Exposure J. Neurosci., May 24, 2006; 26(21): 5810 - 5818. [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]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help