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The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(11)
- Publication Year :
- 2006
-
Abstract
- 金沢大学医薬保健研究域保健学系<br />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. Copyright © 2006 Society for Neuroscience.
- Subjects :
- Male
CB1 receptor
erebellum
Patch-Clamp Techniques
medicine.medical_treatment
Action Potentials
excitatory synapse
Hippocampus
Membrane Potentials
Mice
Purkinje Cells
Piperidines
Receptor, Cannabinoid, CB1
Microscopy, Immunoelectron
6-Cyano-7-nitroquinoxaline-2,3-dione
Mice, Knockout
General Neuroscience
musculoskeletal, neural, and ocular physiology
Pyramidal Cells
food and beverages
Climbing fiber
Articles
cannabinoid
medicine.anatomical_structure
lipids (amino acids, peptides, and proteins)
Female
Rimonabant
psychological phenomena and processes
medicine.drug
Subcellular Fractions
AM251
presynaptic suppression
Morpholines
Purkinje cell
Presynaptic Terminals
Synaptic Membranes
Parallel fiber
Biology
Neurotransmission
Naphthalenes
Depolarization-induced suppression of inhibition
Inhibitory postsynaptic potential
Cerebellar Cortex
Excitatory synapse
Species Specificity
medicine
Animals
Rats, Wistar
pyramidal cell
Benzoxazines
Rats
Mice, Inbred C57BL
nervous system
Pyrazoles
Cannabinoid
Neuroscience
Subjects
Details
- ISSN :
- 15292401
- Volume :
- 26
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....34ac5bf406b7552dcd004f62f40a85ad