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

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.

Suppression of Sleep Spindle Rhythmogenesis in Mice with Deletion of CaV3.2 and CaV3.3 T-type Ca2+ Channels

“…10 Constitutive deletion of this channel has been reported to generate phenotypes not directly related to thalamocortical rhythmogenesis, such as elevated anxiety and impaired memory. [38][39][40] Interestingly, concomitant deletion of CaV3.3 channels appears to override the effect of single CaV3.2 channel deletion on NREM sleep bout distribution. This indicates that the lack of the major T channel subtype for nRt rhythmogenesis imposes a dominant effect of impaired thalamocortical rhythmogenesis on sleep architecture.…”

The Activating Transcription Factor 3 (Atf3) Homozygous Knockout Mice Exhibit Enhanced Conditioned Fear and Down Regulation of Hippocampal GELSOLIN

“…And then furry was removed, skulls were opened. The left and right sides of the hippocampus were then separated and bilateral hippocampi were collected respectively for total RNA extraction, because our previous study found that hippocampal gene expression is lateralized (distinct expression patterns for two sides of the hippocampus) ( Chung et al, 2015 ).…”

Corticohippocampal Dysfunction In The OBiden Mouse Model Of Primary Oligodendrogliopathy

“…While Kv7.2 staining in left CA1 is normal, contralateral Kv7.2 channel staining is significantly reduced. This raises the possibility of asymmetric hippocampal vulnerability to disease, which has been previously observed but is typically associated with behavioral or synaptic asymmetry 77 – 79 . The DAPI labeling in CA1 is comparable between genotypes and rules out major neuron losses in this layer.…”