The authors first showed that in hippocampal slices, neuronal depolarization could evoke both suppression of excitation (depolarization-induced suppression of excitation (DSE)) and potentiation of transmitter release at synapses in an adjacent neuron. Both effects were blocked by inhibition of endocannabinoid release from the postsynaptic neuron with BAPTA or by perfusing hippocampal slices with a CB1R antagonist, indicating that endocannabinoids mediate both DSE and synaptic potentiation (endocannabinoid-mediated synaptic potentiation (eSP)).
The authors next examined whether DSE and eSP are mediated by neuronal and/or astrocytic CB1Rs. Activation of CB1Rs on astrocytes is known to increase intracellular Ca2+ levels, and depleting intracellular Ca2+ from astrocytes abolished eSP but not DSE. In astrocytes, Ca2+ elevation induces glutamate release, which subsequently activates mGluRs on presynaptic neurons and so potentiates neurotransmitter release. The authors showed that perfusing hippocampal slices with an antagonist of group I mGluRs blocked eSP, indicating that this pathway also underlies endocannabinoid-mediated synaptic potentiation. Activation of neuronal CB1Rs activates Gi/o proteins, which are sensitive to pertussis toxin. Treating hippocampal slices with this toxin inhibited endocannabinoid-mediated DSE but increased eSP. Together, these findings show that neuronal CB1Rs mediate DSE, whereas astrocytic CB1Rs — and subsequently neuronal mGluRs — mediate eSP.
This is a preview of subscription content, access via your institution
