Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes
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 hippocamp...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-04-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/24/7/1306 |
| _version_ | 1818199479621255168 |
|---|---|
| author | Lindsey N. Friend Ryan C. Williamson Collin B. Merrill Scott T. Newton Michael T. Christensen Jake Petersen Bridget Wu Isaac Ostlund Jeffrey G. Edwards |
| author_facet | Lindsey N. Friend Ryan C. Williamson Collin B. Merrill Scott T. Newton Michael T. Christensen Jake Petersen Bridget Wu Isaac Ostlund Jeffrey G. Edwards |
| author_sort | Lindsey N. Friend |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T02:22:25Z |
| format | Article |
| id | doaj.art-4db8509799eb459ab62329b7c0cc5726 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T02:22:25Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4db8509799eb459ab62329b7c0cc57262022-12-22T00:41:38ZengMDPI AGMolecules1420-30492019-04-01247130610.3390/molecules24071306molecules24071306Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic EnzymesLindsey N. Friend0Ryan C. Williamson1Collin B. Merrill2Scott T. Newton3Michael T. Christensen4Jake Petersen5Bridget Wu6Isaac Ostlund7Jeffrey G. Edwards8Neuroscience Center, Brigham Young University, Provo, UT 84602, USANeuroscience Center, Brigham Young University, Provo, UT 84602, USADepartment of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USANeuroscience Center, Brigham Young University, Provo, UT 84602, USADepartment of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USADepartment of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USADepartment of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USADepartment of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USANeuroscience Center, Brigham Young University, Provo, UT 84602, USAThe 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.https://www.mdpi.com/1420-3049/24/7/1306anandamideLTPeCBmGluR5mGluR1hippocampusDAGLα12-lipoxygenase |
| spellingShingle | Lindsey N. Friend Ryan C. Williamson Collin B. Merrill Scott T. Newton Michael T. Christensen Jake Petersen Bridget Wu Isaac Ostlund Jeffrey G. Edwards Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes Molecules anandamide LTP eCB mGluR5 mGluR1 hippocampus DAGLα 12-lipoxygenase |
| title | Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes |
| title_full | Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes |
| title_fullStr | Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes |
| title_full_unstemmed | Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes |
| title_short | Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes |
| title_sort | hippocampal stratum oriens somatostatin positive cells undergo cb1 dependent long term potentiation and express endocannabinoid biosynthetic enzymes |
| topic | anandamide LTP eCB mGluR5 mGluR1 hippocampus DAGLα 12-lipoxygenase |
| url | https://www.mdpi.com/1420-3049/24/7/1306 |
| work_keys_str_mv | AT lindseynfriend hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes AT ryancwilliamson hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes AT collinbmerrill hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes AT scotttnewton hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes AT michaeltchristensen hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes AT jakepetersen hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes AT bridgetwu hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes AT isaacostlund hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes AT jeffreygedwards hippocampalstratumorienssomatostatinpositivecellsundergocb1dependentlongtermpotentiationandexpressendocannabinoidbiosyntheticenzymes |