Deletion of the Mouse Homolog of CACNA1C Disrupts Discrete Forms of Hippocampal-Dependent Memory and Neurogenesis within the Dentate Gyrus

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, Ca(V)1.2 is prominently expressed throughout the dentate gyrus. Despite the apparent high levels of Ca(V)1.2 expression in the dentate gyrus, the role of Ca(V)1.2 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 of CACNA1C (Cacna1c), which encodes Ca(V)1.2, with dentate gyrus function implicated in difficult forms of each task. We found that while the deletion of Ca(V)1.2 did not impair the acquisition of fear of a conditioned context, mice lacking Ca(V)1.2 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, Ca(V)1.2 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 Ca(V)1.2 resulted in decreased cell proliferation and the numbers of doublecortin-positive adult-born neurons, implicating Ca(V)1.2 in adult neurogenesis. These results suggest that Ca(V)1.2 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.