Download 00216 - UROP

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.