Presynaptic Specificity of Endocannabinoid Signaling in the Hippocampus
Endocannabinoids are retrograde messengers released by neurons to modulate the strength of their synaptic inputs. Endocannabinoids are thought to mediate the suppression of GABA release that follows depolarization of a hippocampal CA1 pyramidal neuron—termed “depolarization-induced suppression of in...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2001-08, Vol.31 (3), p.453-462 |
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| creator | Wilson, Rachel I. Kunos, George Nicoll, Roger A. |
| description | Endocannabinoids are retrograde messengers released by neurons to modulate the strength of their synaptic inputs. Endocannabinoids are thought to mediate the suppression of GABA release that follows depolarization of a hippocampal CA1 pyramidal neuron—termed “depolarization-induced suppression of inhibition” (DSI). Here, we report that DSI is absent in mice which lack cannabinoid receptor-1 (CB1). Pharmacological and kinetic evidence suggests that CB1 activation inhibits presynaptic Ca
2+ channels through direct G protein inhibition. Paired recordings show that endocannabinoids selectively inhibit a subclass of synapses distinguished by their fast kinetics and large unitary conductance. Furthermore, cannabinoid-sensitive inputs are unusual among central nervous system synapses in that they use N- but not P/Q-type Ca
2+ channels for neurotransmitter release. These results indicate that endocannabinoids are highly selective, rapid modulators of hippocampal inhibition. |
| doi_str_mv | 10.1016/S0896-6273(01)00372-5 |
| format | Article |
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2+ channels through direct G protein inhibition. Paired recordings show that endocannabinoids selectively inhibit a subclass of synapses distinguished by their fast kinetics and large unitary conductance. Furthermore, cannabinoid-sensitive inputs are unusual among central nervous system synapses in that they use N- but not P/Q-type Ca
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2+ channels through direct G protein inhibition. Paired recordings show that endocannabinoids selectively inhibit a subclass of synapses distinguished by their fast kinetics and large unitary conductance. Furthermore, cannabinoid-sensitive inputs are unusual among central nervous system synapses in that they use N- but not P/Q-type Ca
2+ channels for neurotransmitter release. These results indicate that endocannabinoids are highly selective, rapid modulators of hippocampal inhibition.</description><subject>Animals</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channels - physiology</subject><subject>Cannabinoid Receptor Modulators</subject><subject>Cannabinoids - metabolism</subject><subject>Colforsin - pharmacology</subject><subject>Endocannabinoids</subject><subject>Female</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>Hippocampus - physiology</subject><subject>In Vitro Techniques</subject><subject>Interneurons - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Patch-Clamp Techniques</subject><subject>Presynaptic Terminals - drug effects</subject><subject>Presynaptic Terminals - physiology</subject><subject>Pyramidal Cells - drug effects</subject><subject>Pyramidal Cells - physiology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Cannabinoid</subject><subject>Receptors, Drug - deficiency</subject><subject>Receptors, Drug - genetics</subject><subject>Receptors, Drug - physiology</subject><subject>Receptors, Presynaptic - drug effects</subject><subject>Receptors, Presynaptic - physiology</subject><subject>Signal Transduction</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF1LwzAYhYMobk5_gtIr0Ytq3rRJmyuRMTdhoDC9Dmnydka2tDatsH9v94FeenVunnMOPIRcAr0DCuJ-QXMpYsGy5IbCLaVJxmJ-RIZAZRanIOUxGf4iA3IWwielkHIJp2QAwEGkFIZk-tpg2Hhdt85EixqNK51x7SaqymjibWW097pwvnI2Wril1yvnl5HzUfuB0czVdU-s6y6ck5NSrwJeHHJE3p8mb-NZPH-ZPo8f57HhPGtjjtyIvACjs1RgItOCW0GBohQlsyaxAIxZBizFxEhZFAgyTwFLyRlHbZMRud7v1k311WFo1doFg6uV9lh1QWXQL_Ak_xeEvJdAmehBvgdNU4XQYKnqxq11s1FA1Va12qlWW4-KgtqpVrzvXR0OumKN9q91cNsDD3sAex_fDhsVjENv0LoGTats5f65-AHnVY2W</recordid><startdate>20010816</startdate><enddate>20010816</enddate><creator>Wilson, Rachel I.</creator><creator>Kunos, George</creator><creator>Nicoll, Roger A.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20010816</creationdate><title>Presynaptic Specificity of Endocannabinoid Signaling in the Hippocampus</title><author>Wilson, Rachel I. ; Kunos, George ; Nicoll, Roger A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-5e5c68b1ca746e394b5d6010e96f2dc3d1122d2124e3c99bbe19841ef9525ead3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channels - physiology</topic><topic>Cannabinoid Receptor Modulators</topic><topic>Cannabinoids - metabolism</topic><topic>Colforsin - pharmacology</topic><topic>Endocannabinoids</topic><topic>Female</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>Hippocampus - physiology</topic><topic>In Vitro Techniques</topic><topic>Interneurons - physiology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Patch-Clamp Techniques</topic><topic>Presynaptic Terminals - drug effects</topic><topic>Presynaptic Terminals - physiology</topic><topic>Pyramidal Cells - drug effects</topic><topic>Pyramidal Cells - physiology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Cannabinoid</topic><topic>Receptors, Drug - deficiency</topic><topic>Receptors, Drug - genetics</topic><topic>Receptors, Drug - physiology</topic><topic>Receptors, Presynaptic - drug effects</topic><topic>Receptors, Presynaptic - physiology</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wilson, Rachel I.</creatorcontrib><creatorcontrib>Kunos, George</creatorcontrib><creatorcontrib>Nicoll, Roger A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wilson, Rachel I.</au><au>Kunos, George</au><au>Nicoll, Roger A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Presynaptic Specificity of Endocannabinoid Signaling in the Hippocampus</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2001-08-16</date><risdate>2001</risdate><volume>31</volume><issue>3</issue><spage>453</spage><epage>462</epage><pages>453-462</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>Endocannabinoids are retrograde messengers released by neurons to modulate the strength of their synaptic inputs. Endocannabinoids are thought to mediate the suppression of GABA release that follows depolarization of a hippocampal CA1 pyramidal neuron—termed “depolarization-induced suppression of inhibition” (DSI). Here, we report that DSI is absent in mice which lack cannabinoid receptor-1 (CB1). Pharmacological and kinetic evidence suggests that CB1 activation inhibits presynaptic Ca
2+ channels through direct G protein inhibition. Paired recordings show that endocannabinoids selectively inhibit a subclass of synapses distinguished by their fast kinetics and large unitary conductance. Furthermore, cannabinoid-sensitive inputs are unusual among central nervous system synapses in that they use N- but not P/Q-type Ca
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| source | MEDLINE; Cell Press Free Archives; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Calcium Channel Blockers - pharmacology Calcium Channels - physiology Cannabinoid Receptor Modulators Cannabinoids - metabolism Colforsin - pharmacology Endocannabinoids Female GTP-Binding Proteins - metabolism Hippocampus - physiology In Vitro Techniques Interneurons - physiology Male Mice Mice, Inbred C57BL Mice, Knockout Patch-Clamp Techniques Presynaptic Terminals - drug effects Presynaptic Terminals - physiology Pyramidal Cells - drug effects Pyramidal Cells - physiology Rats Rats, Sprague-Dawley Receptors, Cannabinoid Receptors, Drug - deficiency Receptors, Drug - genetics Receptors, Drug - physiology Receptors, Presynaptic - drug effects Receptors, Presynaptic - physiology Signal Transduction |
| title | Presynaptic Specificity of Endocannabinoid Signaling in the Hippocampus |
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