First Author | Moriguchi S | Year | 2019 |
Journal | Mol Neurobiol | Volume | 56 |
Issue | 6 | Pages | 4381-4394 |
PubMed ID | 30324228 | Mgi Jnum | J:318658 |
Mgi Id | MGI:6860109 | Doi | 10.1007/s12035-018-1384-2 |
Citation | Moriguchi S, et al. (2019) Aberrant Amygdala-Dependent Cued Fear Memory in Na(+)/Ca(2+) Exchanger 1 Heterozygous Mice. Mol Neurobiol 56(6):4381-4394 |
abstractText | Na(+)/Ca(2+) exchangers (NCXs) are mainly expressed in the plasma membrane and exchange one Ca(2+) for three Na(+), depending on the electrochemical gradients across the plasma membrane. NCXs have three isoforms, NCX1-3, encoded by distinct genes in mammals. Here, we report that heterozygous mice lacking NCX1 (NCX1(+/-)) exhibit impaired amygdala-dependent cued fear memory. NCX1(+/-) mice showed significant impairment in fear-related behaviors measured with the elevated-plus maze, light-dark, open-field, and marble-burying tasks. In addition, NCX1(+/-) mice showed abnormality in cued fear memory but not in contextual fear memory in a fear-conditioning task. In immunohistochemical analyses, NCX1(+/-) mice had significantly increased number of c-Fos-positive cells in the lateral amygdala (LA) but not in the central amygdala following fear-related tone stimuli. c-Fos expression peaked at 1 h. In concordance with the aberrant fear-related behaviors in NCX1(+/-) mice, enhanced long-term potentiation was also observed in the LA of these mice. Furthermore, enhancement of CaMKII or CaMKIV activity in the LA was observed in NCX1(+/-) mice by immunoblot analyses. In contrast, CaMKII(+/-) but not CaMKIV(-/-) mice insufficiently exhibited tone-induced cued fear memory and there was no increase in the number of c-Fos-positive cells in the LA. Altogether, the increased CaMKII activity and consequent c-Fos expression likely account for the dysregulation of amygdala-dependent cued fear memory in NCX1(+/-) mice. |