Control of synaptic transmission in the CNS through endocannabinoid-mediated retrograde signaling

Psychological and physiological effects of marijuana are caused by binding of its active component (Δ9-tetrahydrocannabinol) to cannabinoid receptors. The cannabinoid receptors belong to a family of G protein-coupled seven-transmembrane-domain receptors, and consist of type 1 (CBl) and type 2 (CB2) receptors with different distributions (Matsuda et al., 1990; Munro et al., 1993; Felder and Glass, 1998). The CBl receptor is expressed in the CNS, whereas the CB2 receptor is found in the immune system of the periphery (Klein et al., 1998). Activation of the CBl receptor induces various effects on neural functions (Di Marzo et al, 1998; Felder and Glass, 1998), including suppression of neurotransmitter release (Gifford and Ashby, 1996; Ishac et al., 1996; Shen et al., 1996; Katona et al, 1999; Hoffman and Lupica, 2000). Several molecules are identified as candidate endogenous ligands for cannabinoid receptors (endocannabinoids). Arachidonylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG), two major endocannabinoids, are reported to be synthesized from membrane phospholipids in an activity- and a Ca2+-dependent manner (Cadas et al, 1996; Stella et al, 1997; Di Marzo et al, 1998; Bisogno et al, 1999; PiomeUi et al, 2000). It is thought that they can diffuse out across the cell membrane. The released endocanabinoids are removed from the extracellular space through uptake and enzymatic degradation (Mechoulam et al, 1998). All these findings suggest that endocannabinoids can work as a diffusible and short-lived mediator that is released from activated neurons, binds to cannabinoid receptors on neighboring neurons to modulate their functions. Recent electrophysiological studies have revealed that endocannabinoids play an important role in retrograde modulation of synaptic transmission in the CNS (Kreitzer and Regehr, 2001b; Maejima et al, 2001a; Ohno-Shosaku et al, 2001; Wilson and NicoU, 2001). Endocannabinoids are released from postsynaptic neurons in response to either depolarization or activation of Gq/11-coupled receptors such as group I metabotropic glutamate receptors (mGluRs) and M1/M3 muscarinic acetylcholine receptors. The released endocannabinoids then activate presynaptic cannabinoid receptors and suppress transmitter release (Maejima et al, 2001b; Alger, 2002; Kano et al, 2002; Kreitzer and Regehr, 2002; Wilson and Nicoll, 2002; Freund et al, 2003; Kano et al., 2003; PiomelU, 2003). Thus, the endocannabinoid signaling is an important mechanism by which postsynaptic neuronal activity can retrogradely influence presynaptic functions. In this review, we introduce recent electrophysiological studies on endocannabinoidmediated retrograde modulation and discuss its possible physiological roles in the CNS.

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Dendritic neurotransmitter release, edited by Mike Ludwig, Springer, c2005, 269-281, (A part of the memoirs)

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http://purl.org/coar/version/c_ab4af688f83e57aa

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2023-07-28 00:57:29.943911

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