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Endocannabinoids contribute to metabotropic glutamate receptor-mediated inhibition of GABA release onto hippocampal CA3 pyramidal neurons in an isolated neuron/bouton preparation.
Neuroscience. 2010 Feb 17; 165(4):1377-89.N

Abstract

Retrograde synaptic signaling by endogenous cannabinoids (endocannabinoids) is a recently discovered form of neuromodulation in various brain regions. In hippocampus, it is well known that endocannabinoids suppress presynaptic inhibitory neurotransmitter release in CA1 region. However, endocannabinoid signaling in CA3 region remains to be examined. Here we investigated whether presynaptic inhibition can be caused by activation of postsynaptic group I metabotropic glutamate receptors (mGluRs) and following presynaptic cannabinoid receptor type 1 (CB1 receptor) using mechanically dissociated rat hippocampal CA3 pyramidal neurons with adherent functional synaptic boutons. Application of group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) reversibly suppressed spontaneous inhibitory postsynaptic currents (IPSCs). In the presence of tetrodotoxin (TTX), frequency of miniature IPSCs was significantly reduced by DHPG, while there were no significant changes in minimum quantal size and sensitivity of postsynaptic GABA(A) receptors to the GABA(A) receptor agonist muscimol, indicating that this suppression was caused by a decrease in GABA release from presynaptic nerve terminals. Application of CB1 synthetic agonist WIN55212-2 (mesylate(R)-(+)-[2,3-dihydro-5-methyl-3-[4-morpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone) or endocannabinoid 2-arachidonoylglycerol also suppressed the spontaneous IPSC. The inhibitory effect of DHPG on spontaneous IPSCs was abolished by SR-141716 (5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide), a CB1 receptor antagonist. Furthermore, postsynaptic application of GDP-betaS blocked the DHPG-induced inhibition of spontaneous IPSCs, indicating the involvement of endcannabinoid-mediated retrograde synaptic signaling. These results provide solid evidence for retrograde signaling from postsynaptic group I mGluRs to presynaptic CB1 receptors, which induces presynaptic inhibition of GABA release in rat hippocampal CA3 region.

Authors+Show Affiliations

Department of Developmental Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19961906

Citation

Inada, H, et al. "Endocannabinoids Contribute to Metabotropic Glutamate Receptor-mediated Inhibition of GABA Release Onto Hippocampal CA3 Pyramidal Neurons in an Isolated Neuron/bouton Preparation." Neuroscience, vol. 165, no. 4, 2010, pp. 1377-89.
Inada H, Maejima T, Nakahata Y, et al. Endocannabinoids contribute to metabotropic glutamate receptor-mediated inhibition of GABA release onto hippocampal CA3 pyramidal neurons in an isolated neuron/bouton preparation. Neuroscience. 2010;165(4):1377-89.
Inada, H., Maejima, T., Nakahata, Y., Yamaguchi, J., Nabekura, J., & Ishibashi, H. (2010). Endocannabinoids contribute to metabotropic glutamate receptor-mediated inhibition of GABA release onto hippocampal CA3 pyramidal neurons in an isolated neuron/bouton preparation. Neuroscience, 165(4), 1377-89. https://doi.org/10.1016/j.neuroscience.2009.11.054
Inada H, et al. Endocannabinoids Contribute to Metabotropic Glutamate Receptor-mediated Inhibition of GABA Release Onto Hippocampal CA3 Pyramidal Neurons in an Isolated Neuron/bouton Preparation. Neuroscience. 2010 Feb 17;165(4):1377-89. PubMed PMID: 19961906.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endocannabinoids contribute to metabotropic glutamate receptor-mediated inhibition of GABA release onto hippocampal CA3 pyramidal neurons in an isolated neuron/bouton preparation. AU - Inada,H, AU - Maejima,T, AU - Nakahata,Y, AU - Yamaguchi,J, AU - Nabekura,J, AU - Ishibashi,H, Y1 - 2009/12/01/ PY - 2009/04/08/received PY - 2009/11/11/revised PY - 2009/11/21/accepted PY - 2009/12/8/entrez PY - 2009/12/8/pubmed PY - 2010/3/13/medline SP - 1377 EP - 89 JF - Neuroscience JO - Neuroscience VL - 165 IS - 4 N2 - Retrograde synaptic signaling by endogenous cannabinoids (endocannabinoids) is a recently discovered form of neuromodulation in various brain regions. In hippocampus, it is well known that endocannabinoids suppress presynaptic inhibitory neurotransmitter release in CA1 region. However, endocannabinoid signaling in CA3 region remains to be examined. Here we investigated whether presynaptic inhibition can be caused by activation of postsynaptic group I metabotropic glutamate receptors (mGluRs) and following presynaptic cannabinoid receptor type 1 (CB1 receptor) using mechanically dissociated rat hippocampal CA3 pyramidal neurons with adherent functional synaptic boutons. Application of group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) reversibly suppressed spontaneous inhibitory postsynaptic currents (IPSCs). In the presence of tetrodotoxin (TTX), frequency of miniature IPSCs was significantly reduced by DHPG, while there were no significant changes in minimum quantal size and sensitivity of postsynaptic GABA(A) receptors to the GABA(A) receptor agonist muscimol, indicating that this suppression was caused by a decrease in GABA release from presynaptic nerve terminals. Application of CB1 synthetic agonist WIN55212-2 (mesylate(R)-(+)-[2,3-dihydro-5-methyl-3-[4-morpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone) or endocannabinoid 2-arachidonoylglycerol also suppressed the spontaneous IPSC. The inhibitory effect of DHPG on spontaneous IPSCs was abolished by SR-141716 (5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide), a CB1 receptor antagonist. Furthermore, postsynaptic application of GDP-betaS blocked the DHPG-induced inhibition of spontaneous IPSCs, indicating the involvement of endcannabinoid-mediated retrograde synaptic signaling. These results provide solid evidence for retrograde signaling from postsynaptic group I mGluRs to presynaptic CB1 receptors, which induces presynaptic inhibition of GABA release in rat hippocampal CA3 region. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/19961906/Endocannabinoids_contribute_to_metabotropic_glutamate_receptor_mediated_inhibition_of_GABA_release_onto_hippocampal_CA3_pyramidal_neurons_in_an_isolated_neuron/bouton_preparation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(09)01965-4 DB - PRIME DP - Unbound Medicine ER -