Endocannabinoid in nonneuronal cells of the CNS

Astrocytes are currently being recognized as key regulatory cells that actively modulate neuronal activity and synaptic transmission by responding to neurotransmitters and releasing gliotransmitters. Through this bidirectional communication with neurons, they participate in many brain functions, such as learning and memory or rhythmic network activity, and influence animal behavior. Endocannabinoid (eCB) signaling, prevalent in many brain regions, plays a critical neuromodulatory role in numerous brain functions and animal behaviors. This review examines and discusses the latest evidence showing that astrocytes detect eCBs released during neuronal activity, which triggers the astrocyte calcium elevations and stimulates the release of gliotransmitters that control synaptic transmission and plasticity. The process of eCB signaling to astrocytes, along with the synaptic regulation by astrocytes triggered by eCBs, is an intricate phenomenon characterized by distinct spatial and temporal features, a multitude of downstream signaling pathways, and a broad range of functional synaptic consequences. Research in this field has uncovered new regulatory mechanisms of synaptic function, such as the distinct eCBs specifically signal to astrocytes and neurons inducing distinct and contrasting synaptic regulation and the direct participation of astrocytes in spike-timing-dependent plasticity, which was previously described as a phenomenon purely governed by neuronal mechanisms in accordance with Hebbian principles of associative learning. Finally, the review also addresses the significant impact of astrocyte-mediated eCB signaling on animal behavior.