Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-04, Vol.24 (7), p.1306
• Main Authors: Friend, Lindsey N, Williamson, Ryan C, Merrill, Collin B, Newton, Scott T, Christensen, Michael T, Petersen, Jake, Wu, Bridget, Ostlund, Isaac, Edwards, Jeffrey G
• Format: Article
• Language: English
• Subjects: 12-lipoxygenase; Anandamide; Animals; Biomarkers; Calcium; Cannabinoid CB1 receptors; DAGLα; Diglycerides; eCB; Endocannabinoids - biosynthesis; Enzymes; Fatty acids; Fatty-acid amide hydrolase; Gene expression; Gene Expression Regulation, Enzymologic; Genes, Reporter; Glutamate receptors; Glutamic acid receptors (metabotropic); Glycerol; Hippocampal plasticity; Hippocampus; Hippocampus - physiology; Hydrolase; Immunohistochemistry; Information processing; Interneurons; Lipase; Lipids; Lipoprotein lipase; Long-Term Potentiation; LTP; mGluR1; mGluR5; Mice; Mice, Knockout; Neuropeptides; Physiology; Plasticity; Polymerase chain reaction; Pyramidal cells; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - metabolism; Reverse transcription; Somatostatin; Somatostatin - metabolism; Stratum radiatum; Synaptic strength
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24071306

The hippocampus is thought to encode information by altering synaptic strength via synaptic plasticity. Some forms of synaptic plasticity are induced by lipid-based endocannabinoid signaling molecules that act on cannabinoid receptors (CB1). Endocannabinoids modulate synaptic plasticity of hippocampal pyramidal cells and stratum radiatum interneurons; however, the role of endocannabinoids in mediating synaptic plasticity of stratum oriens interneurons is unclear. These feedback inhibitory interneurons exhibit presynaptic long-term potentiation (LTP), but the exact mechanism is not entirely understood. We examined whether oriens interneurons produce endocannabinoids, and whether endocannabinoids are involved in presynaptic LTP. Using patch-clamp electrodes to extract single cells, we analyzed the expression of endocannabinoid biosynthetic enzyme mRNA by reverse transcription and then real-time PCR (RT-PCR). The cellular expression of calcium-binding proteins and neuropeptides were used to identify interneuron subtype. RT-PCR results demonstrate that stratum oriens interneurons express mRNA for both endocannabinoid biosynthetic enzymes and the type I metabotropic glutamate receptors (mGluRs), necessary for endocannabinoid production. Immunohistochemical staining further confirmed the presence of diacylglycerol lipase alpha, an endocannabinoid-synthesizing enzyme, in oriens interneurons. To test the role of endocannabinoids in synaptic plasticity, we performed whole-cell experiments using high-frequency stimulation to induce long-term potentiation in somatostatin-positive cells. This plasticity was blocked by AM-251, demonstrating CB1-dependence. In addition, in the presence of a fatty acid amide hydrolase inhibitor (URB597; 1 µM) and MAG lipase inhibitor (JZL184; 1 µM) that increase endogenous anandamide and 2-arachidonyl glycerol, respectively, excitatory current responses were potentiated. URB597-induced potentiation was blocked by CB1 antagonist AM-251 (2 µM). Collectively, this suggests somatostatin-positive oriens interneuron LTP is CB1-dependent.