Figure 10. The mGlu₇ dependent HFS‐induced potentiation is abolished by the lack of Munc13‐2 or RIM1α proteins.

A, changes in the EPSC amplitude induced by two trains (1 s at 50 Hz, every 20 s) in control (untreated) and MSOP (200 μm, 30–60 min) treated slices from Munc13 KO (n = 11 cells/11 slices/4 mice) and WT littermates (n = 11 cells/11 mice/3 mice). B, quantification of the MSOP sensitive component of the EPSC normalized to the basal values prior to HFS. C, changes in EPSC amplitude induced by two trains (1 s at 50 Hz, every 20 s) in control (untreated) and MSOP (200 μm, 30–60 min) treated slices from RIM1α KO (n = 11 cells/11 slices/4 mice) and WT littermates (n = 9 cells/9 mice/3 mice). D, quantification of the MSOP sensitive component of the EPSC normalized to the basal values prior to HFS. Unpaired Student's t test compared to basal values. Scale bars in A and C: 50 pA and 15 ms. EPSC sample traces in A and C represent the mean of 10 consecutive EPSCs at 0.33 Hz 90 s before (basal) and 20 s after HFS (thin and thick traces in the absence and presence of MSOP, respectively). E, scheme of the proposed signalling for the bidirectional modulation of synaptic transmission by mGlu₇ receptors. The mGlu₇ receptor stimulates a PTx‐sensitive G protein that inhibits voltage dependent Ca²⁺ channels and decreases neurotransmitter release. The mGlu₇ receptors also activate a PTx‐resistant G protein to enhance PLC activity, thereby increasing PIP₂ hydrolysis and the generation of DAG. This DAG binds to and activates/translocates the non‐kinase DAG‐binding protein Munc13‐2 to promote glutamate release with the help of RIM1α. DAG, diacylglycerol; HFS, high frequency stimulation; PIP₂, phosphatidylinositol bisphosphate; PLC, phospholipase C; PTx, pertussis toxin; VDCC, voltage dependent Ca²⁺ channel. The blockade/inhibition (dashed line) of Gi/o proteins by PTx, mGlu₇ receptors by MSOP, PLC by U73122 and Munc13 by calphostin C is also indicated, as well as the activation (arrows) of mGlu₇ receptors with the agonist l‐AP4 or by HFS induced glutamate release.