Endocannabinoid signaling in synaptic function

Abstract

In the last decades, astrocytes have emerged as important regulatory cells actively involved in brain function by exchanging signaling with neurons. The endocannabinoid (eCB) signaling is widely present in many brain areas, being crucially involved in multiple brain functions and animal behaviors. The present review presents and discusses current evidence demonstrating that astrocytes sense eCBs released during neuronal activity and subsequently release gliotransmitters that regulate synaptic transmission and plasticity. The eCB signaling to astrocytes and the synaptic regulation mediated by astrocytes activated by eCBs are complex phenomena that exhibit exquisite spatial and temporal properties, a wide variety of downstream signaling mechanisms, and a large diversity of functional synaptic outcomes. Studies investigating this topic have revealed novel regulatory processes of synaptic function, like the lateral regulation of synaptic transmission and the active involvement of astrocytes in the spike-timing dependent plasticity, originally thought to be exclusively mediated by the coincident activity of pre-and postsynaptic neurons, following Hebbian rules for associative learning. Finally, the critical influence of astrocyte-mediated eCB signaling on animal behavior is also discussed.

Astrocytes gate long-term potentiation in hippocampal interneurons

“…Accumulating evidence indicates that neuronal depolarization in the hippocampus induces astrocytic Ca 2+ transients, which are mediated by the activation of astroglial CB1Rs (Eraso-Pichot et al . 2023; Noriega-Prieto et al . 2023; Navarrete & Araque 2008; Navarrete & Araque 2010; Navarrete et al .…”

“…Several independent groups have provided compelling evidence suggesting that astroglial CB1R-mediated signaling pathways regulate excitatory synapses formed by excitatory neurons rather than excitatory synapses between excitatory neurons and interneurons (Fernandez-Moncada & Marsicano 2023; Eraso-Pichot et al . 2023; Noriega-Prieto et al . 2023; Kano et al .…”

“…, intracellular organelles(Jimenez-Blasco et al 2020;Gutierrez-Rodriguez et al 2018) and astrocytes(Ramon-Duaso et al 2023;Noriega-Prieto et al 2023;Eraso-Pichot et al 2023;Fernandez-Moncada & Marsicano 2023;Robin et al 2018;Han et al 2012;Navarrete & Araque 2010;Navarrete & Araque 2008). However, the effects of astroglial CB1R-mediated signaling on synaptic transmission and plasticity are highly debated.…”

rTMS ameliorates depressive‐like behaviors and regulates the gut microbiome and medium‐ and long‐chain fatty acids in mice exposed to chronic unpredictable mild stress

“…Meanwhile, rTMS treatment also increased EPA in the plasma of CUMS‐treated mice effectively, suggesting that these N3 PUFAs were involved in the protective effect of rTMS. Furthermore, AA, a precursor for two main endocannabinoids‐ anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG), plays a key role in modulating synaptic plasticity and neurotransmitter release in the brain 91,92 . Previous work found that serum AA was decreased in childhood and adolescent patients with depression, 93 and a dysfunctional endocannabinoid system (ECS) in the CNS has also been increasingly implicated in the pathophysiology of depression 94 .…”

Modulation of Astroglial Glutamate Transporters by CB1 Receptor Shapes Endocannabinoid-Mediated Long-Term Depression in the Medial Prefrontal Cortex

“…This functional neuro-glial communication relies on calcium (Ca 2+ )-dependent sensing, and gliotransmitter release mechanisms by astrocytes. Endocannabinoids (eCBs) are widespread neuromodulatory molecules that act in the CNS through the activation of the cannabinoid type one receptor (CB1R) 10,11 . In astrocytes, the activation of CB1R induces intracellular Ca 2+ elevations 12 , modulating long-term alterations in synaptic plasticity, namely hippocampal long-term potentiation (LTP) 13 and hippocampal long-term depression (LTD) 14 .…”