Ashley Markham; Lindsey Friend; Ryan Williamson; Collin Merrill; Scott Newton, Brigham Young University
The hippocampus is thought to mediate learning and memory by altering the strength of synapses within its circuitry. In many cases, synaptic plasticity can be induced by signaling molecules. Lipid-based signaling molecules called endocannabinoids, can modulate synaptic plasticity among hippocampal pyramidal cells and stratum radiatum interneurons; however, the role of endocannabinoids in mediating synaptic plasticity among interneurons in the stratum oriens is still unclear. Using patch-clamp electrodes to extract single cells we analyzed the expression of endocannabinoid biosynthetic enzymes’ mRNA using RT-PCR. In this analysis, we examined cellular expression of several calcium-binding proteins and neuropeptides to determine interneuron subtype. We analyzed cellular expression of several endocannabinoid biosynthetic enzymes, including N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), diacylglycerol lipase alpha, and 12-lipoxygenase, as well as type 1 mGluRs. Preliminary data suggests that stratum oriens interneurons express mRNA necessary for endocannabinoid biosynthetic enzymes. To test the role of endocannabinoids in synaptic plasticity, stratum oriens interneurons were patched and glutamate currents were recorded in the presence of a fatty acid amide hydrolase inhibitor (URB597) to increase endogenous anandamide. URB597 potentiated stratum oriens interneurons in a CB1-dependent manner. We have seen a CB1 receptor antagonist (AM-251) abolish the potentiation effect, despite URB597 being present. This implicates CB1 to be mediating the long-term potentiation observed in the stratum oriens interneurons. We suspect that if the CB1 receptor were to be genetically knocked out in rats, whole cell patch-clamp electrophysiology tests would show an abolishment of the observed potentiation. These results demonstrate a novel endocannabinoid-mediated mechanism for synaptic plasticity in stratum oriens interneurons.