title: Deletion of the Mouse Homolog ofCACNA1CDisrupts Discrete Forms of Hippocampal-Dependent Memory and Neurogenesis within the Dentate Gyrus.
abstract: L-type voltage-gated calcium channels (LVGCCs) have been implicated in various forms of learning, memory, and synaptic plasticity. Within the hippocampus, the LVGCC subtype, CaV1.2 is prominently expressed throughout the dentate gyrus. Despite the apparent high levels of CaV1.2 expression in the dentate gyrus, the role of CaV1.2 in hippocampal- and dentate gyrus-associated forms of learning remain unknown. To address this question, we examined alternate forms of hippocampal-dependent associative and spatial memory in mice lacking the mouse ortholog ofCACNA1C(Cacna1c), which encodes CaV1.2, with dentate gyrus function implicated in difficult forms of each task. We found that while the deletion of CaV1.2 did not impair the acquisition of fear of a conditioned context, mice lacking CaV1.2 exhibited deficits in the ability to discriminate between two contexts, one in which the mice were conditioned and one in which they were not. Similarly, CaV1.2 knock-out mice exhibited normal acquisition and recall of the location of the hidden platform in a standard Morris water maze, but were unable to form a memory of the platform location when the task was made more difficult by restricting the number of available spatial cues. Within the dentate gyrus, pan-neuronal deletion of CaV1.2 resulted in decreased cell proliferation and the numbers of doublecortin-positive adult-born neurons, implicating CaV1.2 in adult neurogenesis. These results suggest that CaV1.2 is important for dentate gyrus-associated tasks and may mediate these forms of learning via a role in adult neurogenesis and cell proliferation within the dentate gyrus.
authors.affiliation: Neuroscience Graduate Program, University of Michigan , Ann Arbor, Michigan 48109-0069.
authors.forename: Stephanie J
authors.identifier: 0000-0002-7845-0955
authors.initials: SJ
authors.lastname: Temme
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan , Ann Arbor, Michigan 48109-0069.
authors.forename: Ryan Z
authors.initials: RZ
authors.lastname: Bell
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan , Ann Arbor, Michigan 48109-0069.
authors.forename: Grace L
authors.initials: GL
authors.lastname: Fisher
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48109-0069; Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan 48109-0069; Department of Molecular & Integrative Physiology, School of Medicine, University of Michigan, Ann Arbor, Michigan 48109-0069.
authors.forename: Geoffrey G
authors.initials: GG
authors.lastname: Murphy
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism / Q000473:pathology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000172:deficiency* / Q000235:genetics; D003214:Conditioning, Classical / Q000502:physiology; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D004192:Discrimination, Psychological / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D005239:Fear / Q000502:physiology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D013028:Space Perception / Q000502:physiology
chemical_list: C514350:CACNA1C protein, mouse; D020746:Calcium Channels, L-Type; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
keywords: L-type voltage-gated calcium channel; pattern completion; pattern separation