Endocannabinoids Induce Lateral Long-Term Potentiation of Transmitter Release by Stimulation of Gliotransmission.
Cereb. Cortex. 2014-09-26; 25(10): 3699-3712
DOI: 10.1093/cercor/bhu231
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Gómez-Gonzalo M(1), Navarrete M(2), Perea G(1), Covelo A(3), Martín-Fernández M(3), Shigemoto R(4), Luján R(5), Araque A(6).
Author information:
(1)Instituto Cajal, CSIC, Madrid 28002, Spain.
(2)Instituto Cajal, CSIC, Madrid 28002, Spain Current address: Department of
Neurobiology, Centro de Biología Molecular « Severo Ochoa, » (CSIC/UAM), Madrid,
Spain.
(3)Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455,
USA.
(4)Division of Cerebral Structure, National Institute for Physiological
Sciences, Okazaki 444-8787, Japan.
(5)Instituto de Investigación en Discapacidades Neurológicas (IDINE),
Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La
Mancha, Albacete 02006, Spain.
(6)Instituto Cajal, CSIC, Madrid 28002, Spain Department of Neuroscience,
University of Minnesota, Minneapolis, MN 55455, USA.
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.
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