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Hippocampal GABA B(1a) Receptors Constrain Generalized Contextual Fear.
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2017 Mar; Vol. 42 (4), pp. 914-924. Date of Electronic Publication: 2016 Nov 11. - Publication Year :
- 2017
-
Abstract
- Many anxiety disorders are characterized by generalization of fear responses to neutral or ambiguous stimuli. Therefore, a comprehensive understanding of the mechanisms contributing to generalized fear is essential for formulating successful treatments for anxiety disorders. Previous research shows that GABA-mediated presynaptic inhibition has a critical role in cued fear generalization, as animals with genetically deleted presynaptic GABA <subscript>B(1a)</subscript> receptors cannot discriminate between CS+ and CS- tones. Work from our laboratory has further identified that GABA <subscript>B(1a)</subscript> receptors are necessary for maintaining contextual memory precision, thereby constraining generalized contextual fear. We previously found that GABA <subscript>B(1a)</subscript> KO mice show generalized fear to a neutral context 24 h after training, but not 2 h after training. A similar pattern was observed with object location and recognition, suggesting that this receptor subtype affects consolidation and/or retrieval of precise contextual and spatial memories. Here we sought to specifically examine the involvement of GABA <subscript>B(1a)</subscript> receptors in consolidation or retrieval of a precise fear memory. To do so, we infused a selective GABA <subscript>B(1a)</subscript> receptor antagonist, CGP 36216, intracerebroventricularly (ICV), or locally into the dorsal hippocampus, ventral hippocampus, or anterior cingulate cortex (ACC), during consolidation and retrieval of context fear training. Blockade of GABA <subscript>B(1a)</subscript> receptors through ICV, dorsal hippocampal, or ventral hippocampal infusions 'after' training (consolidation) resulted in fear generalization to the neutral context when mice were tested 24, but not 6 h after training. Post-training infusions of CGP into the ACC, however, did not promote generalized fear. In addition, ICV, dorsal hippocampal, ventral hippocampal, or ACC infusions immediately 'before' testing (retrieval) did not result in context fear generalization. These data suggest that GABA-mediated presynaptic inhibition is not critical for retrieval of precise contextual memory, but rather has an important role in the long-term consolidation of precise contextual memories and constrains generalized fear responses.
- Subjects :
- Animals
Fear drug effects
GABA-B Receptor Antagonists administration & dosage
Generalization, Psychological drug effects
Male
Memory Consolidation drug effects
Mental Recall drug effects
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphinic Acids administration & dosage
Phosphinic Acids pharmacology
Receptors, GABA-A drug effects
Fear physiology
GABA-B Receptor Antagonists pharmacology
Generalization, Psychological physiology
Gyrus Cinguli drug effects
Hippocampus drug effects
Memory Consolidation physiology
Mental Recall physiology
Receptors, GABA-A physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1740-634X
- Volume :
- 42
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 27834391
- Full Text :
- https://doi.org/10.1038/npp.2016.255