Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance
The endogenous cannabinoid, 2-arachidonoylglycerol (2-AG), plays a key role in the regulation of anxiety- and stress-related behavioral phenotypes and may represent a novel target for the treatment of anxiety disorders. However, recent studies have suggested a more complex role for 2-AG signaling in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Neurobiology of Stress |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289522000856 |
| _version_ | 1811173418590011392 |
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| author | Veronika Kondev Rebecca Bluett Mustafa Najeed Luis E. Rosas-Vidal Brad A. Grueter Sachin Patel |
| author_facet | Veronika Kondev Rebecca Bluett Mustafa Najeed Luis E. Rosas-Vidal Brad A. Grueter Sachin Patel |
| author_sort | Veronika Kondev |
| collection | DOAJ |
| description | The endogenous cannabinoid, 2-arachidonoylglycerol (2-AG), plays a key role in the regulation of anxiety- and stress-related behavioral phenotypes and may represent a novel target for the treatment of anxiety disorders. However, recent studies have suggested a more complex role for 2-AG signaling in the regulation of stress responsivity, including increases in acute fear responses after 2-AG augmentation under some conditions. Thus, 2-AG signaling within distinct brain regions and circuits could regulate anxiety-like behavior and stress responsivity in opposing manners. The ventral hippocampus (vHPC) is a critical region for emotional processing, anxiety-like behaviors, and stress responding. Here, we use a conditional knock-out of the 2-AG synthesis enzyme, diacylglycerol lipase α (DAGLα), to study the role of vHPC 2-AG signaling in the regulation of affective behavior. We show that vHPC DAGLα deletion decreases avoidance behaviors both basally and following an acute stress exposure. Genetic deletion of vHPC DAGLα also promotes stress resiliency, with no effect on fear acquisition, expression, or contextual fear generalization. Using slice electrophysiology, we demonstrate that vHPC DAGLα deletion shifts vHPC activity towards enhanced inhibition. Together, these data indicate endogenous 2-AG signaling in the vHPC promotes avoidance and increases stress reactivity, confirming the notion that 2-AG signaling within distinct brain regions may exert divergent effects on anxiety states and stress adaptability. |
| first_indexed | 2024-04-10T17:46:31Z |
| format | Article |
| id | doaj.art-7f5b8aa259804fc28fa10880b96cfb9f |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-04-10T17:46:31Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-7f5b8aa259804fc28fa10880b96cfb9f2023-02-03T04:58:06ZengElsevierNeurobiology of Stress2352-28952023-01-0122100510Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balanceVeronika Kondev0Rebecca Bluett1Mustafa Najeed2Luis E. Rosas-Vidal3Brad A. Grueter4Sachin Patel5Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37232, USAHoward Hughes Medical Institute, University of Washington, Seattle, WA, 98195, USAVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37232, USANorthwestern Center for Psychiatric Neuroscience, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USADepartment of Anesthesiology, Vanderbilt University, Nashville, TN, 37232, USANorthwestern Center for Psychiatric Neuroscience, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA; Corresponding author. Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, USA.The endogenous cannabinoid, 2-arachidonoylglycerol (2-AG), plays a key role in the regulation of anxiety- and stress-related behavioral phenotypes and may represent a novel target for the treatment of anxiety disorders. However, recent studies have suggested a more complex role for 2-AG signaling in the regulation of stress responsivity, including increases in acute fear responses after 2-AG augmentation under some conditions. Thus, 2-AG signaling within distinct brain regions and circuits could regulate anxiety-like behavior and stress responsivity in opposing manners. The ventral hippocampus (vHPC) is a critical region for emotional processing, anxiety-like behaviors, and stress responding. Here, we use a conditional knock-out of the 2-AG synthesis enzyme, diacylglycerol lipase α (DAGLα), to study the role of vHPC 2-AG signaling in the regulation of affective behavior. We show that vHPC DAGLα deletion decreases avoidance behaviors both basally and following an acute stress exposure. Genetic deletion of vHPC DAGLα also promotes stress resiliency, with no effect on fear acquisition, expression, or contextual fear generalization. Using slice electrophysiology, we demonstrate that vHPC DAGLα deletion shifts vHPC activity towards enhanced inhibition. Together, these data indicate endogenous 2-AG signaling in the vHPC promotes avoidance and increases stress reactivity, confirming the notion that 2-AG signaling within distinct brain regions may exert divergent effects on anxiety states and stress adaptability.http://www.sciencedirect.com/science/article/pii/S2352289522000856EndocannabinoidStressVentral hippocampusFear conditioningAnxiety |
| spellingShingle | Veronika Kondev Rebecca Bluett Mustafa Najeed Luis E. Rosas-Vidal Brad A. Grueter Sachin Patel Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance Neurobiology of Stress Endocannabinoid Stress Ventral hippocampus Fear conditioning Anxiety |
| title | Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance |
| title_full | Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance |
| title_fullStr | Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance |
| title_full_unstemmed | Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance |
| title_short | Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance |
| title_sort | ventral hippocampal diacylglycerol lipase alpha deletion decreases avoidance behaviors and alters excitation inhibition balance |
| topic | Endocannabinoid Stress Ventral hippocampus Fear conditioning Anxiety |
| url | http://www.sciencedirect.com/science/article/pii/S2352289522000856 |
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