Genetic deletion of Lsamp causes exaggerated behavioral activation in novel environments

被引:46
作者
Catania, Elizabeth Haldeman [1 ]
Pimenta, Aurea [2 ,3 ]
Levitt, Pat [2 ,3 ]
机构
[1] Vanderbilt Univ, Grad Program Neurosci, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA
关键词
LAMP; limbic system; hyperactivity; anxiety; cell adhesion molecule; knock-out mouse;
D O I
10.1016/j.bbr.2007.11.022
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
The limbic system-associated membrane protein (LAMP) is a GPI-anchored cell adhesion molecule expressed heavily in limbic and limbic-associated regions of the developing and adult brain. Experimental studies show that LAMP promotes the growth of limbic neurons and guides the projections of limbic fibers. In order to examine the functional consequences of disrupting limbic circuit assembly, we generated a mouse line in which the Lsamp gene encoding LAMP was deleted. Basic neuroanatomical organization and sensory and motor development are normal in Lsamp(-/-) mice. The most profound change in behavior in both male and female Lsamp(-/-) mice is a heightened reactivity to novelty exhibited in several behavioral tests. Lsamp(-/-) mice display hyperactivity in a novel arena and both sexes habituate to the same activity levels as their wild type littermates. but at different rates. In the elevated plus maze, Lsamp(-/-) mice exhibit increased total arm entries, with a bias towards the open arms; they spend more time in the open arms and have a substantial increase in the amount of risk assessment in unprotected areas of the maze. In the y-maze. Lsamp(-/-) mice exhibit characteristic hyperactivity and a decreased level of spontaneous alternation during the period when their novelty-induced hyperactivity is at its peak. We hypothesize that Lsamp(-/-) mice may not simply exhibit a decrease in anxiety, but may have a heightened, and possibly maladaptive, response to novel environmental stressors. Genetic deletion of Lsamp may thus cause circumscribed changes in the fine connectivity of specific circuits that underlie these behaviors. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:380 / 390
页数:11
相关论文
共 57 条
  • [1] [Anonymous], 1989, Molecular Cloning
  • [2] Neurodevelopmental origins of depressive disorders
    Ansorge, Mark S.
    Hen, Rene
    Gingrich, Jay A.
    [J]. CURRENT OPINION IN PHARMACOLOGY, 2007, 7 (01) : 8 - 17
  • [3] Ausubel FA, 1998, CURRENT PROTOCOLS MO
  • [4] Barallobre MJ, 2000, DEVELOPMENT, V127, P4797
  • [5] Broca P., 1978, Review Anthropologique, V1, P385
  • [6] Cote PY, 1996, HIPPOCAMPUS, V6, P483
  • [7] DISTRIBUTION OF LIMBIC SYSTEM-ASSOCIATED MEMBRANE-PROTEIN IMMUNOREACTIVITY IN PRIMATE BASAL GANGLIA
    COTE, PY
    LEVITT, P
    PARENT, A
    [J]. NEUROSCIENCE, 1995, 69 (01) : 71 - 81
  • [8] Behavioral assessment of the Ts65Dn mouse, a model for Down syndrome: Altered behavior in the elevated plus maze and open field
    CoussonsRead, ME
    Crnic, LS
    [J]. BEHAVIOR GENETICS, 1996, 26 (01) : 7 - 13
  • [9] Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies
    Crawley, JN
    Belknap, JK
    Collins, A
    Crabbe, JC
    Frankel, W
    Henderson, N
    Hitzemann, RJ
    Maxson, SC
    Miner, LL
    Silva, AJ
    Wehner, JM
    WynshawBoris, A
    Paylor, R
    [J]. PSYCHOPHARMACOLOGY, 1997, 132 (02) : 107 - 124
  • [10] EXPLORATORY-BEHAVIOR MODELS OF ANXIETY IN MICE
    CRAWLEY, JN
    [J]. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 1985, 9 (01) : 37 - 44