Journal: eLife
Article Title: Oxytocin functions as a spatiotemporal filter for excitatory synaptic inputs to VTA dopamine neurons
doi: 10.7554/eLife.33892
Figure Lengend Snippet: ( A ) Left: example traces of evoked EPSCs from one VTA DA neuron during baseline and following 5 μM CB1R agonist WIN55212-2 application. Right: summary data for EPSC amplitude over time, normalized to baseline. ( B ) Left: example traces of evoked EPSCs from one VTA DA neuron during baseline and following 1 μM oxytocin application in the presence of CB1R agonist WIN55212-2. Right: summary data for EPSC amplitude over time, normalized to baseline. ( C ) Same as ( B ), but in the presence of CB1R inverse agonist AM251. ( D ) Same as ( B ), but in the presence of orlistat (THL), a blocker of 2-AG synthesizing enzyme diacylglycerol lipase α (DGLα). ( E ) Same as ( B ), but with THL in the internal solution to block 2-AG synthesis. ( F ) Same as ( B ), but with U73122 in the internal solution to inhibit PLC activity. ( G ) Summary data for EPSC amplitude changes induced by CB1R agonist WIN55212-2 and oxytocin in the presence of WIN55212-2, CB1R inverse agonist AM251, CB1R antagonist CP945598, orlistat (THL), intracellular THL, and intracellular U73122, separately. **p<0.01, Wilcoxon signed rank test vs. baseline. For each condition respectively, n = 7 neurons from five mice, six neurons from four mice, six neurons from three mice, six neurons from four mice, six neurons from four mice, seven neurons from four mice, and seven neurons from four mice. Error bars reflect SEM. ( H ) Schematic summary of the mechanism underlying direct oxytocinergic regulation of excitatory synaptic transmission in VTA DA neurons. Oxytocin binds to G q -coupled OxtR, activating the phospholipase C (PLC) pathway. PLC cleaves phosphatidylinositol 1,4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate, and DAG is subsequently converted into 2-AG by DAG lipase (DGL). 2-AG released by VTA DA neurons binds to presynaptic G i/o -coupled CB1R, decreasing glutamate release. 10.7554/eLife.33892.013 Figure 3—source data 1. Summary tables of evoked EPSC amplitudes in response to endocannabinoid-signaling related pharmacological agents.
Article Snippet: chemical compound, drug , CP945598 hydrochloride , Tocris , Cat#4236; CAS 686347-12-6 , .
Techniques: Blocking Assay, Activity Assay, Transmission Assay