Retrograde signaling

Retrograde signaling is the non-canonical neurotransmission pattern in which a signal travels from the postsynaptic neuron back to the presynaptic terminal, the reverse of the classical direction. Endocannabinoids are the best-characterized retrograde messengers in the mammalian CNS: membrane depolarization or Gq-linked receptor activation in the postsynaptic cell triggers on-demand synthesis of 2-AG (or AEA), which diffuses across the synapse and activates presynaptic CB1 receptors to inhibit neurotransmitter (glutamate or GABA) release. This mechanism underlies depolarization-induced suppression of inhibition (DSI) and excitation (DSE) (Wilson & Nicoll, 2001, Nature 410:588; Kreitzer & Regehr, 2001, Neuron 29:717; Ohno-Shosaku et al., 2001). Retrograde endocannabinoid signaling is central to short- and long-term synaptic plasticity and to the "on-demand" character of ECS activity. → See also: CB1 receptor, 2-AG, Anandamide, Tonic signaling.