Spencer Bell, Brigham Young University
Physiology and Developmental Biology
The hippocampus functions as the memory formation center of the brain. As memories are formed, brain cells in this area undergo changes by which connections between them are either strengthened or weakened, processes known as long-term potentiation (LTP) and long-term depression (LTD), respectively. Receptors located on these cells modulate these processes as they are activated by chemical signals known as neurotransmitters. We sought to examine the effects of a receptor known as G protein-coupled receptor 55 (GPR55) on LTP and LTD in the rodent hippocampus by applying agonists of the receptor, or chemicals that artificially activate it, to brain slices preserved in artificial cerebrospinal fluid. O-1602 is a purported synthetic agonist of GPR55. When we applied O-1602 to rat hippocampal slices during electrical induction of LTP, the magnitude of LTP was decreased when compared to controls. When LTD was induced in the rat hippocampus in the presence of O-1602, no significant difference was observed when compared to controls. Further experimentation involved the application of lysophosphatidylinositol (LPI), a naturally occurring GPR55 agonist, to genetically-engineered knock-out mice which lacked expression of GPR55. LPI is generally considered a more reliable agonist of GPR55, but caused enhanced LTP in wild-type mice which expressed GPR55 when compared with knock-out mice. This inconsistency and other inconsistencies in our data while using O-1602, while perhaps due to other physiological differences between rats and mice, may suggest the possibility that O-1602 activates a receptor other than GPR55. Our further research will seek to investigate this possibility.