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Publication : Aberrant Amygdala-Dependent Cued Fear Memory in Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger 1 Heterozygous Mice.

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.
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