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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.

Deletion of the Mouse Homolog ofCACNA1CDisrupts Discrete Forms of Hippocampal-Dependent Memory and Neurogenesis within the Dentate Gyrus