The L-Type voltage-gated calcium channel Cav1.3 mediates consolidation, but not extinction, of contextually conditioned fear in mice.
Using pharmacological techniques, it has been demonstrated that both consolidation and extinction of Pavlovian fear conditioning are dependent to some extent upon L-type voltage-gated calcium channels (LVGCCs). Although these studies have successfully implicated LVGCCs in Pavlovian fear conditioning, they do not provide information about the specific LVGCC isoform involved. Both of the major LVGCC subtypes found in the brain (Cav1.2 and Cav1.3) are targets of the pharmacological manipulations used in earlier work. In this study, we used mice in which the gene for the pore-forming subunit (alpha1D) Cav1.3 was deleted (Cav1.3 knockout mice) to elucidate its contribution to consolidation and extinction of conditioned fear. We find that Cav1.3 knockout mice exhibit significant impairments in consolidation of contextual fear conditioning. However, once sufficiently overtrained, the Cav1.3 knockout mice exhibit rates of extinction that are identical to that observed in wild-type mice. We also find that Cav1.3 knockout mice perform as well as wild-type mice on the hidden platform version of the Morris water maze, suggesting that the consolidation deficit in conditioned fear observed in the Cav1.3 knockout mice is not likely the result of an inability to encode the context, but may reflect an inability to make the association between the context and the unconditioned stimulus.
McKinney
Brandon C
BC
Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan 48109, USA.
Murphy
Geoffrey G
GG
D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology; D001362:Avoidance Learning / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000145:classification / Q000235:genetics / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D004777:Environment; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants
C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type