ERIC Number: EJ792705
Record Type: Journal
Publication Date: 2008-May
Reference Count: 0
L-type Voltage-Gated Calcium Channels in Conditioned Fear: A Genetic and Pharmacological Analysis
McKinney, Brandon C.; Sze, Wilson; White, Jessica A.; Murphy, Geoffrey G.
Learning & Memory, v15 n5 p326-334 May 2008
Using pharmacological approaches, others have suggested that L-type voltage-gated calcium channels (L-VGCCs) mediate both consolidation and extinction of conditioned fear. In the absence of L-VGCC isoform-specific antagonists, we have begun to investigate the subtype-specific role of LVGCCs in consolidation and extinction of conditioned fear using a molecular genetics approach. Previously, we used this approach to demonstrate that the Ca[subscript-v]1.3 isoform mediates consolidation, but not extinction, of contextually conditioned fear. Here, we used mice in which the gene for the L-VGCC pore-forming subunit Cav1.2 was conditionally deleted in forebrain excitatory neurons (Ca[subscript-v]1.2[superscript cKO] mice) to address the role of Ca[subscript-v]1.2 in consolidation and extinction of conditioned fear. We demonstrate that Ca[subscript-v]1.2[superscript cKO] mice consolidate and extinguish conditioned fear as well as control littermates. These data suggest that Ca[subscript-v]1.2 is not critical for these processes and together with our previous data argue against a role for either of the brain-expressed L-VGCCs (Ca[subscript-v]1.2 or Ca[subscript-v]1.3) in extinction of conditioned fear. Additionally, we present data demonstrating that the L-VGCC antagonist nifedipine, which has been used in previous conditioned fear extinction studies, impairs locomotion, and induces an aversive state. We further demonstrate that this aversive state can enter into associations with conditioned stimuli that are present at the time that it is experienced, suggesting that previous studies using nifedipine were likely confounded by drug toxicity. Taken together, our genetic and pharmacological data argue against a role for Ca[subscript-v]1.2 in consolidation of conditioned fear as well as a role for L-VGCCs in extinction of conditioned fear.
Descriptors: Animals, Genetics, Fear, Pharmacology, Conditioning, Molecular Biology, Brain, Role, Biochemistry, Stimuli
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Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Authoring Institution: N/A