Journal
CEREBRAL CORTEX
Volume 25, Issue 10, Pages 3699-3712Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhu231
Keywords
astrocytes; endocannabinoid signaling; LTP; mGluRs; nitric oxide
Categories
Funding
- Ministerio de Economia y Competitividad, Spain (MINECO) [BFU2010-15832]
- European Union [HEALTH-F2-2007-202167]
- Cajal Blue Brain
- Spain (MINECO) [BFU-2009-08404, CSD2008-00005, CSD2010-00045]
- Ramon y Cajal Program [RYC-2012-12014, BFU2013-47265]
Ask authors/readers for more resources
Endocannabinoids (eCBs) play key roles in brain function, acting as modulatory signals in synaptic transmission and plasticity. They are recognized as retrograde messengers that mediate long-term synaptic depression (LTD), but their ability to induce long-term potentiation (LTP) is poorly known. We show that eCBs induce the long-term enhancement of transmitter release at single hippocampal synapses through stimulation of astrocytes when coincident with postsynaptic activity. This LTP requires the coordinated activity of the 3 elements of the tripartite synapse: 1) eCB-evoked astrocyte calcium signal that stimulates glutamate release; 2) postsynaptic nitric oxide production; and 3) activation of protein kinase C and presynaptic group I metabotropic glutamate receptors, whose location at presynaptic sites was confirmed by immunoelectron microscopy. Hence, while eCBs act as retrograde signals to depress homoneuronal synapses, they serve as lateral messengers to induce LTP in distant heteroneuronal synapses through stimulation of astrocytes. Therefore, eCBs can trigger LTP through stimulation of astrocyte-neuron signaling, revealing novel cellular mechanisms of eCB effects on synaptic plasticity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available