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. 2023 Jun 2;80(6):173. doi: 10.1007/s00018-023-04814-8

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — The role of astrocytic surface and mitochondrial CB1 receptors in lateral synaptic potentiation in the hippocampus. Following high-frequency stimulation of a synapse (A), the plasma membrane-associated CB1 receptors in a contacting astrocyte elicit Ca²⁺ release from the endoplasmic reticulum (B); concomitant stimulation of mitochondrial CB1R (mtCB1R) allows the entry of Ca²⁺ into the mitochondria (B), via the mitochondrial calcium uniporter and using MERCS. It was proposed that the uptake of Ca²⁺ into the mitochondria determines the dynamics of the [Ca²⁺]_i changes in astrocytes, to induce lateral synaptic potentiation (C). The activation of the mtCB1R, which is located in the outer mitochondrial membrane, leads to the inhibition of the sAC (soluble adenylyl cyclase), in turn resulting in a decrease of mitochondrial respiration (D) and consequently in a decrease in energy production. Moreover, the synaptic transmission leads to a stop in mitochondrial trafficking/recruiting in the pre-synaptic compartment (E). The membrane CB1R in the pre-synaptic neuron additionally signals an inhibition in neurotransmitter release (F). (Created with BioRender.com)