Chloe Jensen; Thomas Jarman, Brigham Young University
The hippocampus, a location in the brain associated with learning and memory, has been shown to be a site for synaptic plasticity (the strengthening and weakening of synapses over time based on activity levels). Synaptic plasticity mechanisms such as hippocampal long-term potentiation (LTP) and long-term depression appear to be essential in memory formation. While most classical plasticity studies examined the NMDA receptor, the first receptor identified to mediate LTP, other receptors including cannabinoid receptor CB1 are also involved in various types of hippocampal plasticity. As plasticity is so critical to memory, it is necessary to understand these additional mediators of plasticity in order to provide tools to mitigate memory disorders such as Alzheimer’s disease and dementia, which still lack effective treatments. We previously identified plasticity modification by endocannabinoid pathways that were independent of canonical CB1. Therefore, we examined novel orphan G protein-coupled receptors, GPR18 and GPR119. Both GPR18 and GPR119 can be activated by the endocannabinoid anandamide; GPR18 is also activated by THC and endogenous lipid N-arachidonyl-glycine. Using reverse transcription real-time PCR we identified GPR18 and GPR119 expression in mouse hippocampus. PCR products were isolated by gel electrophoresis to demonstrate the appropriate sized amplicon, which was cut from the gel and sequenced to validate them as GPR18 or GPR 119. To confirm PCR data, we used immunohistochemistry to examine GPR18 and GPR119 protein expression and location. We note antibody labeling of GPR18 in cell bodies of CA1, CA3 and dentate gyrus pyramidal cells. Collectively, our data indicate that GPR18 and GPR119 are expressed in the hippocampus. To determine the potential physiological roles of hippocampal GPR18 and GPR119, we performed field electrophysiology experiments. We found no differences in baseline transmission or in LTP. However, we did find significant differences in post-tetanic potentiation (PTP). We have yet to perform field electrophysiology experiments on GPR119, and also hope to look at CA3 interneuron transmission for both proteins. We then intend to use hippocampal slices from GPR18 and GPR119 knockout mice for field electrophysiology experiments. We believe our research will give important insight as to the location and possible functions of GPR18 and GPR119 in hippocampus function and memory.