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00216 Author: Christopher J. Stapleton Mentor: Daniele Piomelli, Kwang-Mook Jung Title: Activation of Group I Metabotropic Glutamate Receptors Stimulates Endocannabinoid Formation in Brain Slice Cultures Activation of group I metabotropic glutamate (mGlu) receptors causes the endocannabinoid system to induce both short- and long-term changes in synaptic strength in the striatum, the hippocampus, and other regions of the brain. Although current electrophysiological evidence suggests a role for the release of endocannabinoids in mGlu receptor-dependent plasticity, the identity of the specific endocannabinoid transmitter mediating this phenomenon remains ill-defined. In the present study, we show that activation of group I mGlu receptors triggers the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG), but not anandamide, in primary cultures of corticostriatal and hippocampal slices prepared from early postnatal rat brains. Pharmacological studies suggest that the formation of 2-AG requires activation of mGlu5 receptors, is mediated by phospholipase C (PLC) and diacylglycerol lipase (DGL), and is dependent upon the increase of intracellular calcium. Real-time PCR and immunostaining analyses indicate that DGL- is the predominant isoform expressed in corticostriatal slices and is co-localized with PLC- in striatal neurons. These results support a role for 2-AG in mGlu receptor-mediated neuronal plasticity.