Synaptic endocannabinoid signaling

Retrograde Endocannabinoid Signaling in Short-Term Synaptic Depression.447... 

Zhu PJ, Lovinger DM (2005) Retrograde endocannabinoid signaling in a postsynaptic neu-ron/synaptic bouton preparation from basolateral amygdala. J Neurosci 25(26) 6199-6207... 

While the structural bases of COX-2 interaction with AEA have been thoroughly examined (Kozak et al. 2003), indirect evidence for the participation of this enzyme in the inactivation of the endocannabinoid signal in the hippocampus has been reported. In fact, in this brain area, inhibitors of COX-2, but not FAAH, potentiate both short-term and long-term endocannabinoid-mediated synaptic plasticity (Kim and Alger 2004 Slanina and Schweitzer 2005). 

Parkas 1, KaUo 1, DeH L et al (2010) Retrograde endocannabinoid signaling reduces GABAergic synaptic transmission to gonadotropin-releasing hormone neurons. Endocrinology 151 5818-5829... 

Endocannabinoids serve as retrograde messengers. They are released by postsynaptic neurons and act on presynaptic CB1 receptors on neighboring nerve terminals. Retrograde signaling by endocannabinoids is essential for many forms of synaptic plasticity that are initiated by postsynaptic depolarization and increased postsynaptic intracellular Ca2+> but expressed as a presynaptic decrease in the probability of transmitter release. Examples include some forms of long-term depression (LTD see Ch. 53) at GABA... 

Alger, B.E., Retrograde signaling in the regulation of synaptic transmission focus on endocannabinoids. Prog. Neurobiol., 68, 247-286, 2002. 

Presynaptic G-protein coupled receptors for a large number of neurotransmitters, both autoreceptors and receptors for extrinsic signals, suppress Ca2+-channel gating in response to an action potential. This mechanism of action appears to be the dominant mechanism involved in short-term plasticity mediated by presynaptic receptors. A typical example is depolarization-induced suppression of inhibition (DSI), which is the short-term suppression of presynaptic GABA-release induced by the depolarization of the postsynaptic cell (Diana and Marty, 2004). DSI is caused when the postsynaptic depolarization causes the release of endocannabinoids from the postsynaptic cell, and the endocannabinoids then bind to presynaptic CB1 receptors whose activation suppresses presynaptic Ca2+-channels. Like many other forms of presynaptic suppression mediated by activation of presynaptic receptors, this effect is short-lasting (in the millisecond range). The precise mechanisms by which Ca2+-channels are suppressed appear to vary between receptors, but the outcome is always a very effective short-term decrease in synaptic signaling. 

Mackie K. (2006) Mechanisms of CB1 receptor signaling endocannabinoid modulation of synaptic strength. Int. J. Obes. (Lond.) 30 Suppl 1 S 19-23 Mckinney MK, Cravatt, BP (2005) Structure and function of fatty acid amide hydrolase. Annu Rev Biochem 74 411-32... 

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