We investigated the effects of the endocannabinoid-mediated neuron-astrocyte signalling on synaptic transmission in mouse hippocampal slices.
We recorded from CA1 pyramidal neurons and monitored astrocyte Ca2+ levels. We stimulated Schaffer collateral single synapses. Endocannabinoids (ECBs) were released by neuron depolarization (ND) while EPSCs were monitored in an adjacent neuron. We found:
ND transiently increased the probability of transmitter release (Pr) in 40% of the synapses, without affecting EPSC amplitudes, which resulted in a short-term synaptic potentiation (e-SP). These effects were abolished by AM251, and were absent in CB1R-/- mice.
In 27% of the synapses, ND transiently decreased Pr without changing EPSC amplitudes. This was blocked by AM251 and was absent in CB1R-/- mice, like depolarization-induced suppression of excitation (DSE).
ND elevated Ca2+ in astrocytes, which was abolished by AM251 and were absent in CB1R-/- mice.
ND-evoked ECB-mediated e-SP and astrocyte Ca2+ signal were unaffected by pertussis toxin, but were blocked by phospholipase-C antagonists and thapsigargin, indicating that they were not mediated by Gi/o proteins, but by Gq/11 proteins and phospholipase-C-mediated Ca2+ mobilization from internal stores.
After loading astrocytes with BAPTA, DSE was unaffected, but ND failed to induce e-STP.
The ND-evoked e-SP was abolished by the type I mGluR antagonists.
Synapses that showed ND-evoked synaptic potentiation were depressed by CB1R agonists.
When pairing the ND-evoked ECB-mediated astrocytic Ca2+ signal with a mild postsynaptic depolarization, the transient potentiation became persistent.
We conclude that endocannabinoids potentiate excitatory synaptic transmission through stimulation of Ca2+-dependent release of glutamate from astrocytes.
Funded by MICINN (BFU2007-064764) Spain, Cjal Blue Brain, and EU (HEALTH-F2-2007-202167).