Skip to main content
SpringerLink
Log in

Aberrant Amygdala-Dependent Cued Fear Memory in Na+/Ca2+ Exchanger 1 Heterozygous Mice

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Na+/Ca2+ exchangers (NCXs) are mainly expressed in the plasma membrane and exchange one Ca2+ 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

BDNF:

Brain-derived neurotrophic factor

CeA:

Central amygdala

CaN:

Calcineurin

CaMKII:

Calcium/calmodulin-dependent protein kinase II

CaMKIV:

Calcium/calmodulin-dependent protein kinase IV

CREB:

cAMP-responsive element binding protein

ERK:

Extracellular-signal-regulated kinase

fEPSPs:

Field excitatory post-synaptic potentials

LA:

Lateral amygdala

LTP:

Long-term potentiation

NCXs:

Na+/Ca2+ exchangers

NCX1–3 heterozygous:

NCX1–3+/−

PKA:

protein kinase A

WT:

Wild-type

References

  1. Newport DJ, Nemeroff CB (2000) Neurobiology of posttraumatic stress disorder. Curr Opin Neurobiol 10:211–218. https://doi.org/10.1016/S0959-4388(00)00080-5

    Article  CAS  PubMed  Google Scholar 

  2. Pitman RK, Rasmusson AM, Koenen KG et al (2012) Biological studies of post-traumatic stress disorder. Nat Rev Neurosci 13:769–787. https://doi.org/10.1038/nrn3339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yehuda R (2002) Post-traumatic stress disorder. N Engl J Med 346:108–114. https://doi.org/10.1056/NEJMra012941

    Article  CAS  PubMed  Google Scholar 

  4. Yehuda R, LeDoux J (2007) Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron 56:19–32. https://doi.org/10.1016/j.neuron.2007.09.006

    Article  CAS  PubMed  Google Scholar 

  5. Feldman S, Weidenfeld J (1999) Glucocorticoid receptor antagonists in the hippocampus modify the negative feedback following neural stimuli. Brain Res 821:33–37. https://doi.org/10.1016/S0006-8993(99)01054-9

    Article  CAS  PubMed  Google Scholar 

  6. Morimoto M, Morita N, Ozawa H, Yokoyama K, Kawata M (1996) Distribution of glucocorticoid receptor immunoreactivity and mRNA in the rat brain: an immunohistochemical and in situ hybridization study. Neurosci Res 26:235–269. https://doi.org/10.1016/S0168-0102(96)01105-4

    Article  CAS  PubMed  Google Scholar 

  7. Watanabe Y, Gould E, McEwen BS (1992) Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341–345. https://doi.org/10.1016/0006-8993(92)91597-8

    Article  CAS  PubMed  Google Scholar 

  8. Woolley CS, Gould E, McEwen BS (1990) Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225–231. https://doi.org/10.1016/0006-8993(90)90778-A

    Article  CAS  PubMed  Google Scholar 

  9. Sousa N, Luvoyanov NV, Madeira MD et al (2000) Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience 97:253–266. https://doi.org/10.1016/S0306-4522(00)00050-6

    Article  CAS  PubMed  Google Scholar 

  10. Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S (2002) Chronic stress induces contrasting patterns of dendritic remodering in hippocampal and amygdaloid neurons. J Neurosci 22:6810–6818. https://doi.org/10.1523/JNEUROSCI.22-15-06810.2002

    Article  CAS  PubMed  Google Scholar 

  11. Vyas A, Jadhav S, Chattarji S (2006) Prolonged behavioral stress enhances synaptic connectivity in the basolateral amygdala. Neuroscience 143:387–393. https://doi.org/10.1016/j.neuroscience.2006.08.003

    Article  CAS  PubMed  Google Scholar 

  12. Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106:274–285. https://doi.org/10.1037/0735-7044.106.2.274

    Article  CAS  PubMed  Google Scholar 

  13. Matsumoto M, Tachibana K, Togashi H, Tahara K, Kojima T, Yamaguchi T, Yoshioka M (2005) Chronic treatment with milnacipran reverses the impairment of synaptic plasticity induced by conditioned fear stress. Psychopharmacol 179:606–612. https://doi.org/10.1007/s00213-004-2094-1

    Article  CAS  Google Scholar 

  14. McKernan MG, Shinnick-Gallagher P (1997) Fear conditioning induces a lasting potentiation of synaptic currents in vitro. Nature 390:607–611. https://doi.org/10.1038/37605

    Article  CAS  PubMed  Google Scholar 

  15. Rogan MT, Staubli UV, LeDoux JE (1997) Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390:604–607. https://doi.org/10.1038/37601

    Article  CAS  PubMed  Google Scholar 

  16. Blaustein MP, Lederer WJ (1999) Sodium/calcium exchanger: its physiological implications. Physiol Rev 79:763–854. https://doi.org/10.1152/physrev.1999.79.3.763

    Article  CAS  PubMed  Google Scholar 

  17. Annunzaito L, Pignataro G, Di Renzo GF (2004) Pharmacology of brain Na+/Ca2+ exchanger: from molecular biology to therapeutic perspective. Pharmacol Rev 56:633–654. https://doi.org/10.1124/pr.56.4.5

    Article  Google Scholar 

  18. Lipsanen A, Parkkinen S, Khabbal J, Mäkinen P, Peräniemi S, Hiltunen M, Jolkkonen J (2014) KB-R7943, an inhibitor of the reverse Na+/Ca2+ exchanger, does not modify secondary pathology in the thalamus following focal cerebral stroke in rats. Neurosci Lett 580:173–177. https://doi.org/10.1016/j.neulet.2014.08.003

    Article  CAS  PubMed  Google Scholar 

  19. Shenoda B (2015) The role of Na+/Ca2+ exchanger subtypes in neuronal ischemic injury. Transl Stroke Res 6:181–190. https://doi.org/10.1007/s12975-015-0395-9

    Article  CAS  PubMed  Google Scholar 

  20. Nicoll DA, Longoni S, Philipson KD (1990) Molecular cloning and functional expression of the cardiac sacrolemmal Na+/Ca2+ exchanger. Science 250:562–565. https://doi.org/10.1126/science.1700476

    Article  CAS  PubMed  Google Scholar 

  21. Li Z, Matsuoka S, Hryshko LV, Nicoll DA, Bersohn MM, Burke EP, Lifton RP, Philipson KD (1994) Cloning of the NCX2 isoform of the plasma membrane Na+/Ca2+ exchanger. J Biol Chem 269:17434–17439

    CAS  PubMed  Google Scholar 

  22. Quednau BD, Nicoll DA, Philipson KD (1997) Tissue specificity and alternative splicing of the Na+/Ca2+ exchanger isoforms NCX1, NCX2 and NCX3 in rat. Am J Phys 272:C1250–C1261

    Article  CAS  Google Scholar 

  23. Papa M, Canitano A, Boscia F, Castaldo P, Sellitti S, Porzig H, Taglialatela M, Annunziato L (2003) Differential expression of the Na+/Ca2+ exchanger transcripts and proteins in rat brain regions. J Comp Neurol 461:31–48. https://doi.org/10.1002/cne.10665

    Article  CAS  PubMed  Google Scholar 

  24. Jeon D, Yang YM, Jeong MJ, Philipson KD, Rhim H, Shin HS (2003) Enhanced learning and memory in mice lacking Na+/Ca2+ exchanger 2. Neuron 38:965–976. https://doi.org/10.1016/S0896-6273(03)00334-9

    Article  CAS  PubMed  Google Scholar 

  25. Molinaro P, Cuomo O, Pignataro G, Boscia F, Sirabella R, Pannaccione A, Secondo A, Scorziello A et al (2008) Targeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage. J Neurosci 28:1179–1184. https://doi.org/10.1523/JNEUROSCI.4671-07.2008

    Article  CAS  PubMed  Google Scholar 

  26. Moriguchi S, Kita S, Fukaya M, Osanai M, Inagaki R, Sasaki Y, Izumi H, Horie K et al (2018a) Reduced expression of Na+/Ca2+ exchangers is associated with cognitive deficits seen in Alzheimer’s disease model mice. Neuropharmacol 131:291–303

    Article  CAS  Google Scholar 

  27. Wakimoto K, Fujimura H, Iwamoto T, Oka T, Kobayashi K, Kita S, Kudoh S, Kuro-o M et al (2003) Na+/Ca2+ exchanger-deficient mice have disorganized myofibrils and swollen mitochondria in cardiomyocytes. Comp Biochem Physiol B Biochem Mol Biol 135:9–15. https://doi.org/10.1016/S1096-4959(03)00057-5

    Article  CAS  PubMed  Google Scholar 

  28. Gotoh Y, Kita S, Fujii M, Tagashira H, Horie I, Arai Y, Uchida S, Iwamoto T (2015) Genetic knockout and pharmacological inhibition of NCX2 cause natriuresis and hypercalciuria. Biochem Biophys Res Commun 456:670–675. https://doi.org/10.1016/j.bbrc.2014.12.016

    Article  CAS  PubMed  Google Scholar 

  29. Morimoto N, Kita S, Shimazawa M, Namimatsu H, Tsuruma K, Hayakawa K, Mishima K, Egashira N et al (2012) Preferential involvement of Na+/Ca2+ exchanger type-1 in the brain damage caused by transient focal cerebral ischemia in mice. Biochem Biophys Res Commun 429:186–190. https://doi.org/10.1016/j.bbrc.2012.10.114

    Article  CAS  PubMed  Google Scholar 

  30. Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M, Takao K, Tanda K et al (2008) Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. Mol Brain 1:6. https://doi.org/10.1186/1756-6606-1-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Takao K, Tanda K, Nakamura K, Kasahara J, Nakao K, Katsuki M, Nakanishi K, Yamasaki N et al (2010) Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice. PLoS One 5:e9460. https://doi.org/10.1371/journal.pone.0009460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Moriguchi S, Kita S, Yabuki Y, Inagaki R, Izumi H, Sasaki Y, Tagashira H, Horie K, Takeda J, Iwamoto T, Fukunaga K (2017) Reduced CaM kinase II and CaM kinase IV activities underlie cognitive deficits in NCKX2 heterozygous mice. Mol Neurobiol in press. https://doi.org/10.1007/s12035-017-0596-1

  33. Humeau Y, Reisel D, Johnson AW, Borchardt T, Jensen V, Gebhardt C, Bosch V, Gass P et al (2007) A pathway-specific function for different AMPA receptor subunits in amygdala long-term potentiation and fear conditioning. J Neurosci 27:10947–10956. https://doi.org/10.1523/JNEUROSCI.2603-07.2007

    Article  CAS  PubMed  Google Scholar 

  34. Moriguchi S, Ishizuka T, Yabuki Y, Shioda N, Sasaki Y, Tagashira H, Yawo H, Yeh JZ et al (2018b) Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy. Mol Psychiatry 23:211–221

    Article  CAS  Google Scholar 

  35. Iwamoto T, Pan Y, Nakamura TY, Wakabayashi S, Shigekawa M (1998) Protein kinase C-dependent regulation of Na+/Ca2+ exchanger isoforms NCX1 and NCX3 does not require their direct phosphorylation. Biochemistry 37:17230–17238. https://doi.org/10.1021/bi981521q

    Article  CAS  PubMed  Google Scholar 

  36. Fukunaga K, Muller D, Miyamoto E (1995) Increased phosphorylation of Ca2+/calmodulin-dependent protein kinase II and its endogenous substrates in the induction of long term potentiation. J Biol Chem 270:6119–6124. https://doi.org/10.1074/jbc.270.11.6119

    Article  CAS  PubMed  Google Scholar 

  37. Fukunaga K, Horikawa K, Shibata S, Takeuchi Y, Miyamoto E (2002) Ca2+/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin. J Neurosci Res 70:799–807. https://doi.org/10.1002/jnr.10400

    Article  CAS  PubMed  Google Scholar 

  38. Zheng F, Zhou X, Luo Y, Xiao H, Wayman G, Wang H (2011) Regulation of brain-derived neurotrophic factor exon IV transcription through calcium responsive elements in cortical neurons. PLoS One 6:e28441. https://doi.org/10.1371/journal.pone.0028441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kidane AH, Heinrich G, Dirks RP et al (2009) Differential neuroendocrine expression of multiple brain-derived neurotrophic factor transcripts. Endocrinology 150:1361–1368. https://doi.org/10.1210/en.2008-0993

    Article  CAS  PubMed  Google Scholar 

  40. Maren S, Fanselow MS (1996) The amygdala and fear conditioning: has the nut been cracked? Neuron 16:237–240. https://doi.org/10.1016/S0896-6273(00)80041-0

    Article  CAS  PubMed  Google Scholar 

  41. Goosens KA, Maren S (2002) Long-term potentiation as a substrate for memory: evidence from studies of amygdaloid plasticity and Pavlovian fear conditioning. Hippocampus 12:592–599. https://doi.org/10.1002/hipo.10099

    Article  PubMed  Google Scholar 

  42. Huang YY, Kandel ER (1998) Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala. Neuron 21:169–178. https://doi.org/10.1016/S0896-6273(00)80524-3

    Article  CAS  PubMed  Google Scholar 

  43. Tsvetkov E, Carlezon WA, Benes FM et al (2002) Fear conditioning occludes LTP-induced presynaptic enhancement of synaptic transmission in the cortical pathway to the lateral amygdala. Neuron 34:289–300. https://doi.org/10.1016/S0896-6273(02)00645-1

    Article  CAS  PubMed  Google Scholar 

  44. Chen C, Rainnie DG, Greene RW, Tonegawa S (1994) Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II. Science 266:291–294. https://doi.org/10.1126/science.7939668

    Article  CAS  PubMed  Google Scholar 

  45. Hasegawa S, Furuichi T, Yoshida T, Endoh K, Kato K, Sado M, Maeda R, Kitamoto A et al (2009) Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression. Mol Brain 2:6. https://doi.org/10.1186/1756-6606-2-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ho N, Liauw JA, Blaeser F, Wei F, Hanissian S, Muglia LM, Wozniak DF, Nardi A et al (2000) Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase IV/Gr-deficient mice. J Neurosci 20:6459–6472. https://doi.org/10.1523/JNEUROSCI.20-17-06459.2000

    Article  CAS  PubMed  Google Scholar 

  47. Xia Z, Storm DR (2005) The role of calmodulin as a signal integrator for synaptic plasticity. Nat Rev Neurosci 6:267–276. https://doi.org/10.1038/nrn1647

    Article  CAS  PubMed  Google Scholar 

  48. Huang YY, Martin KC, Kandel ER (2000) Both protein kinase A and mitogen-activated protein kinase are required in the amygdala for the macromolecular synthesis-dependent late phase of long-term potentiation. J Neurosci 20:6317–6325. https://doi.org/10.1523/JNEUROSCI.20-17-06317.2000

    Article  CAS  PubMed  Google Scholar 

  49. Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20:709–726. https://doi.org/10.1016/S0896-6273(00)81010-7

    Article  CAS  PubMed  Google Scholar 

  50. Endres T, Lessmann V (2012) Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice. Learn Mem 19:561–570. https://doi.org/10.1101/lm.028068.112

    Article  CAS  PubMed  Google Scholar 

  51. Chou D, Huang CC, Hsu KS (2014) Brain-derived neurotrophic factor in the amygdala mediates susceptibility to fear conditioning. Exp Neurol 255:19–29. https://doi.org/10.1016/j.expneurol.2014.02.016

    Article  CAS  PubMed  Google Scholar 

  52. Meis S, Endres T, Munsch T et al (2017) The relation between long-term synaptic plasticity at glutamatergic synapses in the amygdala and fear learning in adult heterozygous BDNF-knockout mice. Cereb Cortex 10:1–14

    Google Scholar 

  53. Li C, Dabrowska J, Hazra R, Rainnie DG (2011) Synergistic activation of dopamine D1 and TrkB receptors mediate gain control of synaptic plasticity in the basolateral amygdala. PLoS One 6:e26065. https://doi.org/10.1371/journal.pone.0029303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Daftary SS, Calderon G, Rios M (2012) Essential role of brain-derived neurotrophic factor in the regulation of serotonin transmission in the basolateral amygdala. Neuroscience 224:125–134. https://doi.org/10.1016/j.neuroscience.2012.08.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Meis S, Endres T, Lessmann V (2012) Postsynaptic BDNF signaling regulates long-term potentiation at thalamo-amygdala afferents. J Physiol 590:193–208. https://doi.org/10.1113/jphysiol.2011.220434

    Article  CAS  PubMed  Google Scholar 

  56. Rattiner LM, Davis M, Ressler KJ (2004) Differential regulation of brain-derived neurotrophic factor transcripts during the consolidation of fear learning. Learn Mem 11:727–731. https://doi.org/10.1101/lm.83304

    Article  PubMed  Google Scholar 

  57. Ou LC, Gean PW (2006) Regulation of amygdala-dependent learning by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol-3-kinase. Neuropsychopharmacol 31:287–296

    Article  CAS  Google Scholar 

  58. Moriguchi S, Sakagami H, Yabuki Y, Sasaki Y, Izumi H, Zhang C, Han F, Fukunaga K (2015) Stimulation of sigma-1 receptor ameliorates depressive-like behaviors in CaMKIV null mice. Mol Neurobiol 52:1210–1222. https://doi.org/10.1007/s12035-014-8923-2

    Article  CAS  PubMed  Google Scholar 

  59. Hagiwara M, Brindle P, Harootunian A, Armstrong R, Rivier J, Vale W, Tsien R, Montminy MR (1993) Coupling of hormonal stimulation and transcription via the cyclic AMP-responsive factor CREB is rate limited by nuclear entry of protein kinase A. Mol Cell Biol 13:4852–4859. https://doi.org/10.1128/MCB.13.8.4852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sokolow S, Luu SH, Headley A et al (2011) High levels of synaptosomal Na+/Ca2+ exchangers (NCX1, NCX2, NCX3) co-localized with amyloid-beta in human cerebral cortex affected by Alzheimer’s disease. Cell Calcium 49:208–216. https://doi.org/10.1016/j.ceca.2010.12.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Profs. Issei Komuro and Tsuyoshi Miyakawa for providing the NCX1+/− and CaMKIIα+/− mice, respectively.

Funding

This work financially was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology and the Ministry of Health and Welfare of Japan (KAKENHI 22390109 to K.F., 20790398 to S.M., 16K08565 to S.K., 17K08610 to T.I.), the Smoking Research Foundation (to S.M.), and Mochida Memorial Foundation for Medical and Pharmaceutical Research (to S.M), and Takeda Science Foundation (S.M.).

Author information

Authors and Affiliations

  1. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, Miyagi, 980-8578, Japan

    Shigeki Moriguchi, Ryo Inagaki, Yasushi Yabuki, Yuzuru Sasaki, Shun Ishikawa & Kohji Fukunaga

  2. Department of Pharmacology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, Fukuoka, 814-0180, Japan

    Satomi Kita & Takahiro Iwamoto

  3. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan

    Satomi Kita

  4. Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan

    Hiroyuki Sakagami

Authors
  1. Shigeki Moriguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satomi Kita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryo Inagaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasushi Yabuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuzuru Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shun Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroyuki Sakagami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takahiro Iwamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kohji Fukunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.M., R.I., Y.Y., Y.S., and S.I. performed the experiments. S.K. and T.I. generated the NCX2+/− and NCX3+/− mouse lines and NCX antibodies, and provided experimental advice. S.H. provided the CaMKIV−/− mice. S.M. and K.F. wrote the manuscript and designed the study.

Corresponding authors

Correspondence to Shigeki Moriguchi or Takahiro Iwamoto.

Ethics declarations

Ethical Approval

All animal protocols were approved by the Committee of Animal Experiments at Tohoku University.

Conflict of Interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moriguchi, S., Kita, S., Inagaki, R. et al. Aberrant Amygdala-Dependent Cued Fear Memory in Na+/Ca2+ Exchanger 1 Heterozygous Mice. Mol Neurobiol 56, 4381–4394 (2019). https://doi.org/10.1007/s12035-018-1384-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-018-1384-2

Keywords

Search

Navigation