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The Journal of Neuroscience, May 3, 2006, 26(18):4740-4751; doi:10.1523/JNEUROSCI.0054-06.2006

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Cellular/Molecular
Localization of Diacylglycerol Lipase- around Postsynaptic Spine Suggests Close Proximity between Production Site of an Endocannabinoid, 2-Arachidonoyl-glycerol, and Presynaptic Cannabinoid CB1 Receptor

Takayuki Yoshida,^1,2,3 Masahiro Fukaya,¹ Motokazu Uchigashima,¹ Eriko Miura,¹ Haruyuki Kamiya,² Masanobu Kano,³ and Masahiko Watanabe¹

Departments of ¹Anatomy or ²Molecular Neuroanatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, and ³Department of Cellular Neuroscience, Graduate School of Medical Science, Osaka University, Suita 565-0871, Japan

Correspondence should be addressed to Masahiko Watanabe, Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan. Email: watamasa{at}med.hokudai.ac.jp

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. To understand the mechanisms of the 2-AG-mediated retrograde modulation, we investigated subcellular localization of a major 2-AG biosynthetic enzyme, diacylglycerol lipase- (DAGL), by using immunofluorescence and immunoelectron microscopy in the mouse brain. In the cerebellum, DAGL was predominantly expressed in Purkinje cells. DAGL was detected on the dendritic surface and occasionally on the somatic surface, with a distal-to-proximal gradient from spiny branchlets toward somata. DAGL was highly concentrated at the base of spine neck and also accumulated with much lower density on somatodendritic membrane around the spine neck. However, DAGL was excluded from the main body of spine neck and head. In hippocampal pyramidal cells, DAGL was also accumulated in spines. In contrast to the distribution in Purkinje cells, DAGL was distributed in the spine head, neck, or both, whereas somatodendritic membrane was labeled very weakly. These results indicate that DAGL 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. The preferential spine targeting should enable efficient 2-AG production on excitatory synaptic activity and its swift retrograde modulation onto nearby presynaptic terminals expressing CB1. Furthermore, different fine localization within and around spines suggests that the distance between postsynaptic 2-AG production site and presynaptic CB1 is differentially controlled depending on neuron types.

Key words: endocannabinoid; 2-arachidonoyl-glycerol; 2-AG; diacylglycerol lipase; DAGL; CB1; immunohistochemistry; Purkinje cell; hippocampal pyramidal cell; mouse

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Received Jan. 6, 2006; revised March 18, 2006; accepted March 20, 2006.

Correspondence should be addressed to Masahiko Watanabe, Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan. Email: watamasa{at}med.hokudai.ac.jp

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