These results indicate that DAGLα is essentially targeted to postsynaptic spines in cerebellar and hippocampal neurons, but its fine distribution within and around spines is differently regulated between the two neurons. ![]() ![]() In contrast to the distribution in Purkinje cells, DAGLα was distributed in the spine head, neck, or both, whereas somatodendritic membrane was labeled very weakly. In hippocampal pyramidal cells, DAGLα was also accumulated in spines. However, DAGLα was excluded from the main body of spine neck and head. DAGLα was highly concentrated at the base of spine neck and also accumulated with much lower density on somatodendritic membrane around the spine neck. DAGLα was detected on the dendritic surface and occasionally on the somatic surface, with a distal-to-proximal gradient from spiny branchlets toward somata. ![]() In the cerebellum, DAGLα was predominantly expressed in Purkinje cells. To understand the mechanisms of the 2-AG-mediated retrograde modulation, we investigated subcellular localization of a major 2-AG biosynthetic enzyme, diacylglycerol lipase-α (DAGLα), by using immunofluorescence and immunoelectron microscopy in the mouse brain. 2-Arachidonoyl-glycerol (2-AG) is an endocannabinoid that is released from postsynaptic neurons, acts retrogradely on presynaptic cannabinoid receptor CB1, and induces short- and long-term suppression of transmitter release.
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