Endocannabinoid-Mediated Long-Term Plasticity Requires cAMP/PKA Signaling and RIM1α

Vivien Chevaleyre, Boris D. Heifets, Pascal S. Kaeser, Thomas C. Südhof, Dominick P. Purpura, Pablo E. Castillo

Research output: Contribution to journalArticle

171 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)801-812
Number of pages12
JournalNeuron
Volume54
Issue number5
DOIs
StatePublished - Jun 7 2007

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Long-Term Synaptic Depression
Cannabinoid Receptor CB1
Endocannabinoids
Hippocampus
Presynaptic Receptors
Brain
Amygdala
Proteins

Keywords

  • MOLNEURO
  • SIGNALING
  • SYSNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chevaleyre, V., Heifets, B. D., Kaeser, P. S., Südhof, T. C., Purpura, D. P., & Castillo, P. E. (2007). Endocannabinoid-Mediated Long-Term Plasticity Requires cAMP/PKA Signaling and RIM1α. Neuron, 54(5), 801-812. https://doi.org/10.1016/j.neuron.2007.05.020

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 journalArticle

Chevaleyre, V, Heifets, BD, Kaeser, PS, Südhof, TC, Purpura, DP & Castillo, PE 2007, 'Endocannabinoid-Mediated Long-Term Plasticity Requires cAMP/PKA Signaling and RIM1α', Neuron, vol. 54, no. 5, pp. 801-812. https://doi.org/10.1016/j.neuron.2007.05.020
Chevaleyre, Vivien ; Heifets, Boris D. ; Kaeser, Pascal S. ; Südhof, Thomas C. ; Purpura, Dominick P. ; Castillo, Pablo E. / Endocannabinoid-Mediated Long-Term Plasticity Requires cAMP/PKA Signaling and RIM1α. In: Neuron. 2007 ; Vol. 54, No. 5. pp. 801-812.
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