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Behavior training reverses asymmetry in hippocampal transcriptome of the cav3.2 knockout mice.

Chung NC, Huang YH, Chang CH, Liao JC, Yang CH, Chen CC, Liu IY - PLoS ONE (2015)

Bottom Line: We found a significant left-right asymmetric effect on the hippocampal transcriptome caused by the Cav3.2 knockout.Remarkably, the effect of Cav3.2 knockout was partially reversed by trace fear conditioning.To our knowledge, these results demonstrate for the first time the asymmetric effects of the Cav3.2 and its partial reversal by behavior training on the hippocampal transcriptome.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan.

ABSTRACT
Homozygous Cav3.2 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 Cav3.2 in global gene expression, we performed a microarray transcriptome study on the hippocampi of the Cav3.2-/- 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 Cav3.2 knockout. Between the naive Cav3.2-/- 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 Cav3.2 knockout was partially reversed by trace fear conditioning. The number of DEGs in the left hippocampus was reduced to 6 in the Cav3.2 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 Cav3.2 and its partial reversal by behavior training on the hippocampal transcriptome.

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Behavioral analysis.(a) Locomotor activity for all groups measured during the first 120 seconds of the training protocol showed that the Cav3.2 knockout mice are as normal as their wild-type littermates. (b) The Cav3.2 knockout mice were impaired in retrieval of contextual memory tested 24 hours post the TFC training protocol. (WN: wild-type naïve group; KN: knockout naïve group; WT: wild-type training group; KT: knockout training group; * p<.05)
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pone.0118832.g002: Behavioral analysis.(a) Locomotor activity for all groups measured during the first 120 seconds of the training protocol showed that the Cav3.2 knockout mice are as normal as their wild-type littermates. (b) The Cav3.2 knockout mice were impaired in retrieval of contextual memory tested 24 hours post the TFC training protocol. (WN: wild-type naïve group; KN: knockout naïve group; WT: wild-type training group; KT: knockout training group; * p<.05)

Mentions: To investigate the role of the Cav3.2 and the effect of TFC on the Cav3.2-/- mice, we used microarrays to probe the transcriptome of naïve (N) and trained (T) groups for both wild-type (W) and the Cav3.2 homozygous knockout (K) mice. Wild-type C57BL/6J male mice were maintained undisturbed in the laboratory animal center until the behavioral tasks were performed. The Cav3.2-/- mice were generated and genotyped as described previously [23]. Mice were trace fear conditioned individually and then tested with contextual memory 24 hours later in the same conditioning chamber. Immediately after memory testing, left (L) and right (R) hippocampi from three W and three knockout animals were dissected, pooled together to extract RNA. The RNA samples were amplified, reverse-transcribed to cDNA and labeled, and then hybridized to Mouse Whole Genome OneArray TM (MOAV1.1) with 29,922 mouse genome probes and 1880 experimental control probes. A total of eight groups of samples were analyzed: WNL, WNR, WTL, WTR, KNL, KNR, KTL, and KTR (Fig. 1A). The overall experimental design was illustrated in Fig. 1B. In order to reconfirm the phenotype of the Cav3.2 knockout mice, we analyzed their behavioral data after TFC. Fig. 2A showed that the Cav3.2 knockout mice demonstrated normal locomotor activity and Fig. 2B showed that their contextual memory retrieval was impaired as compared with their wild-type littermates. The deficiency in retrieval of contextual memory is consistent with our previous study [19], and demonstrates the robustness of the effect.


Behavior training reverses asymmetry in hippocampal transcriptome of the cav3.2 knockout mice.

Chung NC, Huang YH, Chang CH, Liao JC, Yang CH, Chen CC, Liu IY - PLoS ONE (2015)

Behavioral analysis.(a) Locomotor activity for all groups measured during the first 120 seconds of the training protocol showed that the Cav3.2 knockout mice are as normal as their wild-type littermates. (b) The Cav3.2 knockout mice were impaired in retrieval of contextual memory tested 24 hours post the TFC training protocol. (WN: wild-type naïve group; KN: knockout naïve group; WT: wild-type training group; KT: knockout training group; * p<.05)
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4358833&req=5

pone.0118832.g002: Behavioral analysis.(a) Locomotor activity for all groups measured during the first 120 seconds of the training protocol showed that the Cav3.2 knockout mice are as normal as their wild-type littermates. (b) The Cav3.2 knockout mice were impaired in retrieval of contextual memory tested 24 hours post the TFC training protocol. (WN: wild-type naïve group; KN: knockout naïve group; WT: wild-type training group; KT: knockout training group; * p<.05)
Mentions: To investigate the role of the Cav3.2 and the effect of TFC on the Cav3.2-/- mice, we used microarrays to probe the transcriptome of naïve (N) and trained (T) groups for both wild-type (W) and the Cav3.2 homozygous knockout (K) mice. Wild-type C57BL/6J male mice were maintained undisturbed in the laboratory animal center until the behavioral tasks were performed. The Cav3.2-/- mice were generated and genotyped as described previously [23]. Mice were trace fear conditioned individually and then tested with contextual memory 24 hours later in the same conditioning chamber. Immediately after memory testing, left (L) and right (R) hippocampi from three W and three knockout animals were dissected, pooled together to extract RNA. The RNA samples were amplified, reverse-transcribed to cDNA and labeled, and then hybridized to Mouse Whole Genome OneArray TM (MOAV1.1) with 29,922 mouse genome probes and 1880 experimental control probes. A total of eight groups of samples were analyzed: WNL, WNR, WTL, WTR, KNL, KNR, KTL, and KTR (Fig. 1A). The overall experimental design was illustrated in Fig. 1B. In order to reconfirm the phenotype of the Cav3.2 knockout mice, we analyzed their behavioral data after TFC. Fig. 2A showed that the Cav3.2 knockout mice demonstrated normal locomotor activity and Fig. 2B showed that their contextual memory retrieval was impaired as compared with their wild-type littermates. The deficiency in retrieval of contextual memory is consistent with our previous study [19], and demonstrates the robustness of the effect.

Bottom Line: We found a significant left-right asymmetric effect on the hippocampal transcriptome caused by the Cav3.2 knockout.Remarkably, the effect of Cav3.2 knockout was partially reversed by trace fear conditioning.To our knowledge, these results demonstrate for the first time the asymmetric effects of the Cav3.2 and its partial reversal by behavior training on the hippocampal transcriptome.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan.

ABSTRACT
Homozygous Cav3.2 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 Cav3.2 in global gene expression, we performed a microarray transcriptome study on the hippocampi of the Cav3.2-/- 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 Cav3.2 knockout. Between the naive Cav3.2-/- 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 Cav3.2 knockout was partially reversed by trace fear conditioning. The number of DEGs in the left hippocampus was reduced to 6 in the Cav3.2 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 Cav3.2 and its partial reversal by behavior training on the hippocampal transcriptome.

Show MeSH