Endocannabinoid Signaling and Synaptic Function

• Published in: Neuron (Cambridge, Mass.) Vol. 76; no. 1; pp. 70 - 81
• Main Authors: Castillo, Pablo E., Younts, Thomas J., Chávez, Andrés E., Hashimotodani, Yuki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.10.2012; Elsevier Limited
• Subjects: Animals; Brain; Brain - physiology; Endocannabinoids - metabolism; Humans; Ligands; Lipids; Medical research; Neuronal Plasticity - physiology; Proteins; Receptors, Cannabinoid - physiology; Signal Transduction - physiology; Synaptic Transmission - physiology
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2012.09.020

Endocannabinoids are key modulators of synaptic function. By activating cannabinoid receptors expressed in the central nervous system, these lipid messengers can regulate several neural functions and behaviors. As experimental tools advance, the repertoire of known endocannabinoid-mediated effects at the synapse, and their underlying mechanism, continues to expand. Retrograde signaling is the principal mode by which endocannabinoids mediate short- and long-term forms of plasticity at both excitatory and inhibitory synapses. However, growing evidence suggests that endocannabinoids can also signal in a nonretrograde manner. In addition to mediating synaptic plasticity, the endocannabinoid system is itself subject to plastic changes. Multiple points of interaction with other neuromodulatory and signaling systems have now been identified. In this Review, we focus on new advances in synaptic endocannabinoid signaling in the mammalian brain. The emerging picture not only reinforces endocannabinoids as potent regulators of synaptic function but also reveals that endocannabinoid signaling is mechanistically more complex and diverse than originally thought. Endocannabinoids are key modulators of synaptic function, and endocannabinoid signaling is more mechanistically complex and diverse than originally thought. In this Review, Castillo et al. focus on new advances in endocannabinoid signaling and highlight the role of endocannabinoids as potent regulators of synaptic function.