Learning and cemory in the cav1.2 knockout mouse

Of the many signaling pathways found within neurons, calcium signaling is perhaps the most ubiquitous and versatile. Calcium influx through L-type voltage-gated calcium channels (L-VGCCs) is involved in numerous aspects of neuronal function: activation and regulation of gene transcription, synaptic plasticity, and regulation of neuronal excitability are all modulated by calcium. Because many calcium-related subcellular functions are implicated in the formation and storage of long-term memory, this writer investigated the role of an L-VGCC, CaV1.2, in hippocampus-dependent learning and memory. Utilizing the Cre/loxP gene-targeting system, the CaV1.2 L-VGCC isoform was conditionally deleted in the forebrain of mice. This extensive deletion was confirmed by RT-PCR and Immunoblotting. To test for spatial learning and memory, a series of Morris water maze experiments were performed. Knockout mice showed no deficits in short-term (24-hr) memory trials; however, on a 30-day memory probe, knockout mice performed significantly more poorly than their littermate controls. These results indicate the importance of forebrainspecific CaV1.2 for long-term spatial memory