Stimulation of Endocannabinoid Formation in Brain Slice Cultures through Activation of Group I Metabotropic Glutamate Receptors

Abstract

Activation of group I metabotropic glutamate (mGlu) receptors drives the endocannabinoid system to cause both shortand long-term changes of synaptic strength in the striatum, hippocampus, and other brain areas. Although there is strong electrophysiological evidence for a role of endocannabinoid release in mGlu receptor-dependent plasticity, the identity of the endocannabinoid transmitter mediating this phenomenon remains undefined. In this 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 brain.Pharmacological studies suggest that 2-AG biosynthesis is initiated by activation of mGlu5 receptors, is catalyzed by phospholipase C (PLC) and 1,2-diacylglycerol lipase (DGL) activities, and is dependent on intracellular Ca 2ϩ ions. Realtime polymerase chain reaction and immunostaining analyses indicate that DGL-␤ is the predominant DGL isoform expressed in corticostriatal and hippocampal slices and that this enzyme is highly expressed in striatal neurons, where it is colocalized with PLC-␤1. The results suggest that 2-AG is a primary endocannabinoid mediator of mGlu receptor-dependent neuronal plasticity.

Glutamate Spillover Modulates GABAergic Synaptic Transmission in the Rat Midbrain Periaqueductal Grey via Metabotropic Glutamate Receptors and Endocannabinoid Signaling

“…In support of this, it has been shown that mGluR5 colocalizes with diacylglycerol lipase-␣, the synthetic enzyme of the endocannabinoid 2-arachidonoylglycerol (2-AG), in perisynaptic regions of striatal medium spiny neurons (Uchigashima et al, 2007). In addition, group I mGluR activation initiates 2-AG biosynthesis (Jung et al, 2005) and endocannabinoid-mediated synaptic plasticity in several other brain regions (Ohno-Shosaku et al, 2002;Zhu and Lovinger, 2005;Grueter et al, 2006;Centonze et al, 2007;Uchigashima et al, 2007). In the present study, we have not identified the endocannabinoid involved; however, anandamide and 2-AG are potential candidates, because they are both produced within the PAG under certain conditions (Walker et al, 1999;Hohmann et al, 2005).…”

Pannexin-1-mediated ATP release from area CA3 drives mGlu5-dependent neuronal oscillations

“…Slices were pre-incubated with the mGlu5 receptor antagonist MPEP (Gasparini et al, 1999) at 5 µM (Jung et al, 2005). Slices were exposed to MPEP for 10 minutes after which DHPG was applied ( Figure 2E).…”

A neuroscientist's guide to lipidomics

“…In particular, the endocannabinoid 2-AG has been directly implicated in mGlur-induced retrograde signalling in the hippocampus, cerebellum and other regions of the brain [60][61][62] . It is envisaged that 2-AG may be produced in dendritic spines, through activation of type I mGlurs and the transducing G-protein G q/11 , which are coupled to the phospholipase C/DAG lipase (DGl) pathway (fIG.…”

“…4). Glutamate (blue circles) released from excitatory axon terminals activates postsynaptic type I metabotropic glutamate receptors (mGluR), stimulating 2-AG production through the phospholipase C-β (PLC-β)/diacylglycerol lipase (DGL) pathway 60 (fIG. 4).…”