Behavior Training Reverses Asymmetry in Hippocampal Transcriptome of the Ca(v)3.2 Knockout Mice

Homozygous Ca(v)3.2 knockout mice, which are defective in the pore-forming subunit of a low voltage activated T-type calcium channel, have been documented to show impaired maintenance of late-phase long-term potentiation (L-LTP) and defective retrieval of context-associated fear memory. To investigate the role of Ca(v)3.2 in global gene expression, we performed a microarray transcriptome study on the hippocampi of the Ca(v)3.2(-/-) mice and their wild-type littermates, either naïve (untrained) or trace fear conditioned. We found a significant left-right asymmetric effect on the hippocampal transcriptome caused by the Ca(v)3.2 knockout. Between the naive Ca(v)3.2(-/-) and the naive wild-type mice, 3522 differentially expressed genes (DEGs) were found in the left hippocampus, but only 4 DEGs were found in the right hippocampus. Remarkably, the effect of Ca(v)3.2 knockout was partially reversed by trace fear conditioning. The number of DEGs in the left hippocampus was reduced to 6 in the Ca(v)3.2 knockout mice after trace fear conditioning, compared with the wild-type naïve mice. To our knowledge, these results demonstrate for the first time the asymmetric effects of the Ca(v)3.2 and its partial reversal by behavior training on the hippocampal transcriptome.