Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems.
Iron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2(hipp/hipp) mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2(hipp/hipp) mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2(hipp/hipp) mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems.


BACKGROUND
The online version of this article (doi:10.1007/s11689-010-9049-0) contains supplementary material, which is available to authorized users.
Carlson
Erik S
ES
Fretham
Stephanie J B
SJ
Unger
Erica
E
O'Connor
Michael
M
Petryk
Anna
A
Schallert
Timothy
T
Rao
Raghavendra
R
Tkac
Ivan
I
Georgieff
Michael K
MK
J Neurosci. 1999 Apr 1;19(7):2789-98
10087090
J Nutr. 2003 Apr;133(4):1174-9
12672939
Neuron. 2007 Sep 6;55(5):686-9
17785176
Neurobiol Learn Mem. 2004 Nov;82(3):333-46
15464414
Magn Reson Med. 1999 Apr;41(4):649-56
10332839
J Cereb Blood Flow Metab. 2007 May;27(5):1055-63
17033694
Behav Brain Res. 2006 Jun 30;170(2):224-32
16569441
J Clin Invest. 2005 May;115(5):1258-66
15849611
Neuron. 2005 Jun 2;46(5):703-13
15924857
Neurotox Res. 2010 Apr;17(3):238-47
19655216
J Nutr. 2007 Apr;137(4):1043-9
17374674
Am J Psychiatry. 2002 Jul;159(7):1080-92
12091183
Behav Brain Res. 2002 Aug 21;134(1-2):517-24
12191838
Arch Gen Psychiatry. 2008 Oct;65(10):1136-44
18838630
J Pediatr. 1992 Jul;121(1):109-14
1625067
J Psychiatry Neurosci. 2004 Jul;29(4):282-6
15309044
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17163-8
18955704
Semin Pediatr Neurol. 2006 Sep;13(3):158-65
17101454
Dev Sci. 2009 Mar;12(2):209-19
19143795
Schizophr Res. 2004 Dec 1;71(2-3):213-25
15474893
Magn Reson Med. 2000 Feb;43(2):319-23
10680699
Hippocampus. 2005;15(8):1094-102
16187331
Trends Neurosci. 2008 May;31(5):234-42
18395805
Magn Reson Med. 2004 Sep;52(3):478-84
15334565
J Pediatr. 1990 Sep;117(3):455-61
2391604
Behav Neurosci. 2007 Jun;121(3):475-82
17592938
Infant Behav Dev. 2009 Dec;32(4):366-75
19592115
J Psychiatry Neurosci. 2008 Sep;33(5):395-404
18787655
J Pediatr Psychol. 2010 Apr;35(3):296-305
19736288
Schizophr Bull. 2011 Sep;37(5):982-7
20093425
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9887-92
8790426
J Nutr. 2003 Oct;133(10):3215-21
14519813
Sleep Med. 2004 Nov;5(6):593-6
15511707
Behav Brain Res. 2009 Dec 7;204(2):295-305
19100784
J Nutr. 1999 Jan;129(1):199-206
9915900
Brain Res Brain Res Rev. 1998 Dec;28(3):370-490
9858769
J Nutr. 2007 Mar;137(3):683-9
17311960
Am J Med Genet. 2000 Spring;97(1):65-71
10813806
J Nutr. 2007 Apr;137(4):979-84
17374664
Eur J Neurosci. 2002 May;15(10):1692-706
12059977
Neuropharmacology. 1980 Mar;19(3):259-67
6252501
J Pediatr. 2008 May;152(5):696-702, 702.31-3
18410777
Magn Reson Med. 1993 Dec;30(6):672-9
8139448
Magn Reson Med. 1993 Jun;29(6):804-11
8350724
Pediatr Res. 2005 May;57(5 Pt 2):99R-103R
15817493
Am Psychol. 2001 Jan;56(1):5-15
11242988
J Neurosci Res. 2007 Nov 15;85(15):3340-6
17526022
Genesis. 2000 Feb;26(2):133-5
10686608
Behav Brain Res. 2002 Oct 17;136(1):113-26
12385796
Neuroscientist. 2000 Feb;6(1):5-13
18461153
Pediatr Res. 2004 Jun;55(6):1034-41
15155871
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5644-9
17372196
J Neurochem. 1994 Jan;62(1):329-37
8263532
Pharmacotherapy. 2009 Jun;29(6):656-79
19476419
Pediatrics. 2007 Aug;120(2):e336-45
17671043
J Lipid Res. 1984 Dec 15;25(13):1548-54
6397559
Dev Neurosci. 2003 Nov-Dec;25(6):412-20
14966382
J Nutr. 2009 Apr;139(4):672-9
19211831
Behav Neural Biol. 1994 May;61(3):260-70
8067981
J Magn Reson. 1999 Nov;141(1):104-20
10527748
Neuroscience. 2008 Jan 2;151(1):43-55
18082335
J Nutr. 1996 Mar;126(3):693-701
8598555
Neurobiol Learn Mem. 2002 Mar;77(2):125-84
11848717
Pediatr Res. 2000 Aug;48(2):169-76
10926291
Behav Neurosci. 1992 Jun;106(3):439-46
1616610
J Neurosci. 2007 Oct 17;27(42):11424-30
17942737
Exp Brain Res. 2008 May;187(3):419-27
18330551
Pediatr Res. 2007 Dec;62(6):715-9
17957147
J Cereb Blood Flow Metab. 2007 Apr;27(4):729-40
16868555
Behav Brain Res. 2006 Aug 10;171(2):261-70
16713640
Annu Rev Nutr. 1986;6:13-40
3524613