Behavior Training Reverses Asymmetry in Hippocampal Transcriptome of the Cav3.2 Knockout Mice

Homozygous Ca_v3.2 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_v3.2 in global gene expression, we performed a microarray transcriptome study on the hippocampi of the Ca_v3.2^-/- 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_v3.2 knockout. Between the naive Ca_v3.2^-/- 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_v3.2 knockout was partially reversed by trace fear conditioning. The number of DEGs in the left hippocampus was reduced to 6 in the Ca_v3.2 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_v3.2 and its partial reversal by behavior training on the hippocampal transcriptome.