Abstract
Endocannabinoids (eCBs) have emerged as key activity-dependent signals that, by activating presynaptic cannabinoid receptors (i.e., CB1) coupled to Gi/o protein, can mediate short-term and long-term synaptic depression (LTD). While the presynaptic mechanisms underlying eCB-dependent short-term depression have been identified, the molecular events linking CB1 receptors to LTD are unknown. Here we show in the hippocampus that long-term, but not short-term, eCB-dependent depression of inhibitory transmission requires presynaptic cAMP/PKA signaling. We further identify the active zone protein RIM1α as a key mediator of both CB1 receptor effects on the release machinery and eCB-dependent LTD in the hippocampus. Moreover, we show that eCB-dependent LTD in the amygdala and hippocampus shares major mechanistic features. These findings reveal the signaling pathway by which CB1 receptors mediate long-term effects of eCBs in two crucial brain structures. Furthermore, our results highlight a conserved mechanism of presynaptic plasticity in the brain.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 801-812 |
| Number of pages | 12 |
| Journal | Neuron |
| Volume | 54 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jun 7 2007 |
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Keywords
- MOLNEURO
- SIGNALING
- SYSNEURO
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Endocannabinoid-Mediated Long-Term Plasticity Requires cAMP/PKA Signaling and RIM1α. / Chevaleyre, Vivien; Heifets, Boris D.; Kaeser, Pascal S.; Südhof, Thomas C.; Purpura, Dominick P.; Castillo, Pablo E.
In: Neuron, Vol. 54, No. 5, 07.06.2007, p. 801-812.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endocannabinoid-Mediated Long-Term Plasticity Requires cAMP/PKA Signaling and RIM1α
AU - Chevaleyre, Vivien
AU - Heifets, Boris D.
AU - Kaeser, Pascal S.
AU - Südhof, Thomas C.
AU - Purpura, Dominick P.
AU - Castillo, Pablo E.
PY - 2007/6/7
Y1 - 2007/6/7
N2 - Endocannabinoids (eCBs) have emerged as key activity-dependent signals that, by activating presynaptic cannabinoid receptors (i.e., CB1) coupled to Gi/o protein, can mediate short-term and long-term synaptic depression (LTD). While the presynaptic mechanisms underlying eCB-dependent short-term depression have been identified, the molecular events linking CB1 receptors to LTD are unknown. Here we show in the hippocampus that long-term, but not short-term, eCB-dependent depression of inhibitory transmission requires presynaptic cAMP/PKA signaling. We further identify the active zone protein RIM1α as a key mediator of both CB1 receptor effects on the release machinery and eCB-dependent LTD in the hippocampus. Moreover, we show that eCB-dependent LTD in the amygdala and hippocampus shares major mechanistic features. These findings reveal the signaling pathway by which CB1 receptors mediate long-term effects of eCBs in two crucial brain structures. Furthermore, our results highlight a conserved mechanism of presynaptic plasticity in the brain.
AB - Endocannabinoids (eCBs) have emerged as key activity-dependent signals that, by activating presynaptic cannabinoid receptors (i.e., CB1) coupled to Gi/o protein, can mediate short-term and long-term synaptic depression (LTD). While the presynaptic mechanisms underlying eCB-dependent short-term depression have been identified, the molecular events linking CB1 receptors to LTD are unknown. Here we show in the hippocampus that long-term, but not short-term, eCB-dependent depression of inhibitory transmission requires presynaptic cAMP/PKA signaling. We further identify the active zone protein RIM1α as a key mediator of both CB1 receptor effects on the release machinery and eCB-dependent LTD in the hippocampus. Moreover, we show that eCB-dependent LTD in the amygdala and hippocampus shares major mechanistic features. These findings reveal the signaling pathway by which CB1 receptors mediate long-term effects of eCBs in two crucial brain structures. Furthermore, our results highlight a conserved mechanism of presynaptic plasticity in the brain.
KW - MOLNEURO
KW - SIGNALING
KW - SYSNEURO
UR - http://www.scopus.com/inward/record.url?scp=34249691285&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249691285&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2007.05.020
DO - 10.1016/j.neuron.2007.05.020
M3 - Article
C2 - 17553427
AN - SCOPUS:34249691285
VL - 54
SP - 801
EP - 812
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 5
ER -