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Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step.
Proc Natl Acad Sci U S A. 2007 Dec 18; 104(51):20564-9.PN

Abstract

Endocannabinoids (eCBs) mediate short- and long-term depression of synaptic strength by retrograde transsynaptic signaling. Previous studies have suggested that an eCB mobilization or release step in the postsynaptic neuron is involved in this retrograde signaling. However, it is not known whether this release process occurs automatically upon eCB synthesis or whether it is regulated by other synaptic factors. To address this issue, we loaded postsynaptic striatal medium spiny neurons (MSNs) with the eCBs anandamide (AEA) or 2-arachidonoylglycerol and determined the conditions necessary for presynaptic inhibition. We found that presynaptic depression of glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) induced by postsynaptic eCB loading required a certain level of afferent activation that varied between the different synaptic types. Synaptic depression at excitatory synapses was temperature-dependent and blocked by the eCB membrane transport blockers, VDM11 and UCM707, but did not require activation of metabotropic glutamate receptors, l-calcium channels, nitric oxide, voltage-activated Na(+) channels, or intracellular calcium. Application of the CB(1)R antagonist, AM251, after depression was established, reversed the decrease in EPSC, but not in IPSC, amplitude. Direct activation of the CB(1) receptor by WIN 55,212-2 initiated synaptic depression that was independent of afferent stimulation. These findings indicate that retrograde eCB signaling requires a postsynaptic release step involving a transporter or carrier that is activated by afferent stimulation/synaptic activation.

Authors+Show Affiliations

Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health, Bethesda, MD 20892, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18077376

Citation

Adermark, Louise, and David M. Lovinger. "Retrograde Endocannabinoid Signaling at Striatal Synapses Requires a Regulated Postsynaptic Release Step." Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 51, 2007, pp. 20564-9.
Adermark L, Lovinger DM. Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step. Proc Natl Acad Sci U S A. 2007;104(51):20564-9.
Adermark, L., & Lovinger, D. M. (2007). Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step. Proceedings of the National Academy of Sciences of the United States of America, 104(51), 20564-9.
Adermark L, Lovinger DM. Retrograde Endocannabinoid Signaling at Striatal Synapses Requires a Regulated Postsynaptic Release Step. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20564-9. PubMed PMID: 18077376.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step. AU - Adermark,Louise, AU - Lovinger,David M, Y1 - 2007/12/11/ PY - 2007/12/14/pubmed PY - 2008/1/29/medline PY - 2007/12/14/entrez SP - 20564 EP - 9 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 104 IS - 51 N2 - Endocannabinoids (eCBs) mediate short- and long-term depression of synaptic strength by retrograde transsynaptic signaling. Previous studies have suggested that an eCB mobilization or release step in the postsynaptic neuron is involved in this retrograde signaling. However, it is not known whether this release process occurs automatically upon eCB synthesis or whether it is regulated by other synaptic factors. To address this issue, we loaded postsynaptic striatal medium spiny neurons (MSNs) with the eCBs anandamide (AEA) or 2-arachidonoylglycerol and determined the conditions necessary for presynaptic inhibition. We found that presynaptic depression of glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) induced by postsynaptic eCB loading required a certain level of afferent activation that varied between the different synaptic types. Synaptic depression at excitatory synapses was temperature-dependent and blocked by the eCB membrane transport blockers, VDM11 and UCM707, but did not require activation of metabotropic glutamate receptors, l-calcium channels, nitric oxide, voltage-activated Na(+) channels, or intracellular calcium. Application of the CB(1)R antagonist, AM251, after depression was established, reversed the decrease in EPSC, but not in IPSC, amplitude. Direct activation of the CB(1) receptor by WIN 55,212-2 initiated synaptic depression that was independent of afferent stimulation. These findings indicate that retrograde eCB signaling requires a postsynaptic release step involving a transporter or carrier that is activated by afferent stimulation/synaptic activation. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/18077376/Retrograde_endocannabinoid_signaling_at_striatal_synapses_requires_a_regulated_postsynaptic_release_step_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=18077376 DB - PRIME DP - Unbound Medicine ER -