Identification of the synthetic pathway producing the endocannabinoid that mediates the bulk of retrograde signaling in the brain.

Endocannabinoids serve as retrograde messengers that are released by postsynaptic cells to regulate neurotransmitter release from presynaptic boutons. A new study in this issue of Neuron by Tanimura et al. establishes that most endocannabinoid signaling in the brain is a consequence of the calcium-dependent or receptor-driven generation of the retrograde signal 2-arachidonoylglycerol (2-AG) by diacylglycerol lipase alpha (DGLalpha).