抄録
Upon depolarization and Gq protein-coupled receptor activation, endocannabinoids are synthesized in postsynaptic neurons and act on presynaptic CB1 receptor, causing endocannabinoid-mediated retrograde suppression (ERS) of transmitter release at activated excitatory synapses and nearby inhibitory synapses. Through immunohistochemical studies on distribution and localization of CB1, endocannabinoid synthetic enzyme diacylglycerol lipase (DAGL), and relevant receptors, the following facts are disclosed so far. In Purkinje cells, CB1 is highly expressed at both excitatory and inhibitory synapses, and DAGLa accumulates at the neck of dendritic spines. Notably, DAGLa is selectively excluded from the spine head, at which mGluR1 is exclusively concentrated. In hippocampal pyramidal cells, CB1 is expressed at much higher levels in CCK interneuron synapses than excitatory synapses, and, reciprocally, DAGLa is confined to dendritic spines forming excitatory synapses. In the striatum, CB1 is highly expressed at medium spiny neuron (MSN)-MSN neuron synapse and parvalbumin interneuron-MSN synapse, with lower levels at corticostriatal synapses. In MSNs, DAGLa and mGluR5 exhibit similar gradient-like distribution with the highest level in dendritic spines and gradual decrease toward the soma, while muscarinic acetylcholine receptor M1 is more evenly distributed. Therefore, the occurrence of physiological ERS at excitatory and inhibitory synapses are regulated, at least partly, through these different fine synaptic localization of endocannabinoid signaling molecules in given neurons forming distinct synaptic organization. [J Physiol Sci. 2007;57 Suppl:S48]
