Exploratory, anxiety and spatial memory impairments are dissociated in mice lacking the LPA1 receptor.
Lysophosphatidic acid (LPA) is a new, intercellular signalling molecule in the brain that has an important role in adult hippocampal plasticity. Mice lacking the LPA(1) receptor exhibit motor, emotional and cognitive alterations. However, the potential relationship among these concomitant impairments was unclear. Wild-type and maLPA(1)-null mice were tested on the hole-board for habituation and spatial learning. MaLPA(1)-null mice exhibited reduced exploration in a novel context and a defective intersession habituation that also revealed increased anxiety-like behaviour throughout the hole-board testing. In regard to spatial memory, maLPA(1) nulls failed to reach the controls' performance at the end of the reference memory task. Moreover, their defective working memory on the first training day suggested a delayed acquisition of the task's working memory rule, which is also a long term memory component. The temporal interval between trials and the task's difficulty may explain some of the deficits found in these mice. Principal components analysis revealed that alterations found in each behavioural dimension were independent. Therefore, exploratory and emotional impairments did not account for the cognitive deficits that may be attributed to maLPA(1) nulls' hippocampal malfunction.
Castilla-Ortega
Estela
E
Departamento de Psicobiología y Metodología de las CC, Universidad de Málaga, Campus de Teatinos, 29071 Málaga, Spain.
Sánchez-López
Jorge
J
Hoyo-Becerra
Carolina
C
Matas-Rico
Elisa
E
Zambrana-Infantes
Emma
E
Chun
Jerold
J
De Fonseca
Fernando Rodríguez
FR
Pedraza
Carmen
C
Estivill-Torrús
Guillermo
G
Santin
Luis J
LJ
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009483:Neuropsychological Tests; D025341:Principal Component Analysis; D049368:Receptors, Lysophosphatidic Acid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology; D013997:Time Factors
D049368:Receptors, Lysophosphatidic Acid
Behav Brain Res. 1994 Mar 31;61(1):59-64
7913324
Psychopharmacology (Berl). 2007 May;192(1):39-48
17242924
Nat Neurosci. 2003 Dec;6(12):1292-9
14625558
Brain Res Cogn Brain Res. 1996 Jun;3(3-4):167-81
8806020
Bioessays. 2004 Aug;26(8):870-81
15273989
Genes Brain Behav. 2007 Jun;6(4):389-400
16939636
Hippocampus. 2006;16(3):216-24
16421862
Exp Neurol. 2006 Feb;197(2):330-40
16309676
Prostaglandins Other Lipid Mediat. 2005 Sep;77(1-4):46-51
16099390
Pharmacol Biochem Behav. 1998 Jun;60(2):473-88
9632231
Cereb Cortex. 2008 Apr;18(4):938-50
17656621
Biol Psychiatry. 2000 Dec 15;48(12):1157-63
11137057
Brain Res Bull. 1981 Aug;7(2):221-6
7272800
Behav Neurosci. 2002 Jun;116(3):464-71
12049327
Neuropsychologia. 1979;17(6):669-82
522981
Genes Brain Behav. 2004 Jun;3(3):149-57
15140010
Behav Neurosci. 2003 Oct;117(5):1044-53
14570553
Learn Mem. 2008 Feb 19;15(3):97-105
18285468
Rev Physiol Biochem Pharmacol. 2008;160:25-46
18481029
Neurosci Biobehav Rev. 1998;22(1):33-57
9491939
Neurobiol Learn Mem. 2006 Sep;86(2):150-9
16580234
Curr Drug Targets. 2007 Jan;8(1):155-67
17266539
Nature. 1982 Jun 24;297(5868):681-3
7088155
Cell Mol Life Sci. 2006 Dec;63(23):2695-701
16988788
J Biol Chem. 2004 May 14;279(20):20555-8
15023998
Annu Rev Biochem. 2004;73:321-54
15189145
Genes Brain Behav. 2009 Nov;8(8):772-84
19689455
Eur J Neurosci. 1998 Mar;10(3):1045-53
9753172
Brain Res. 1997 Aug 8;765(1):37-50
9310392
Behav Brain Res. 2002 Aug 21;134(1-2):49-57
12191791
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13384-9
11087877
Psychoneuroendocrinology. 1998 Jan;23(1):33-44
9618750
Mol Cell Neurosci. 2003 Dec;24(4):1170-9
14697676
J Neurosci. 2001 Nov 15;21(22):9077-81
11698618
Brain Res. 1971 Nov;34(1):171-5
5124915
J Neurochem. 2006 Jun;97(5):1379-92
16638019
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4642-6
17360577
Neurosci Biobehav Rev. 2006;30(7):1045-64
16774787
Curr Opin Pharmacol. 2009 Feb;9(1):15-23
19119080
Neuroreport. 2006 Apr 3;17(5):523-6
16543818
Mol Cell Neurosci. 2008 Nov;39(3):342-55
18708146
Eur J Pharmacol. 1998 May 29;350(1):21-9
9683010
Eur J Neurosci. 2004 Jun;19(12):3151-64
15217371
Eur J Neurosci. 2003 Jan;17(1):128-36
12534976
Biochim Biophys Acta. 2008 Sep;1781(9):531-9
18407842
Neuroscience. 1999;93(1):243-51
10430488
Behav Brain Res. 2006 Mar 15;168(1):92-9
16310870
Learn Mem. 2002 Sep-Oct;9(5):224-37
12359832
J Neurosci. 2006 Mar 8;26(10):2767-76
16525056
Learn Mem. 2003 Mar-Apr;10(2):108-15
12663749
Behav Brain Res. 1998 Mar;91(1-2):73-81
9578441
Neurochem Res. 2005 Mar;30(3):371-7
16018581
Annu Rev Pharmacol Toxicol. 2001;41:507-34
11264467
Neurobiol Learn Mem. 1999 Sep;72(2):78-94
10438649
Eur J Neurosci. 2006 Jul;24(2):595-605
16903861
Pharmacol Biochem Behav. 1999 Dec;64(4):731-8
10593196
Mol Cell Neurosci. 2002 Jun;20(2):271-82
12093159
Learn Mem. 2008 Oct 02;15(10):733-46
18832560
Hippocampus. 1998;8(2):138-46
9572720
Annu Rev Pharmacol Toxicol. 2010;50:157-86
20055701
Behav Pharmacol. 2005 May;16(3):171-80
15864072
Schizophr Res. 2006 Feb 28;82(2-3):175-83
16414245