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血清素转运体基因敲除小鼠的运动模式、探索行为的时空组织及空间记忆

Locomotory patterns, spatiotemporal organization of exploration and spatial memory in serotonin transporter knockout mice.

作者信息

Kalueff Allan V, Jensen Catherine L, Murphy Dennis L

机构信息

Laboratory of Clinical Science, Building 10, Room 3D41, National Institute of Mental Health, 10 Center Dr. MSC 1264, Bethesda, MD 20892-1264, USA.

出版信息

Brain Res. 2007 Sep 12;1169:87-97. doi: 10.1016/j.brainres.2007.07.009. Epub 2007 Jul 14.

DOI:10.1016/j.brainres.2007.07.009
PMID:17692295
Abstract

Serotonin transporter knockout (SERT-/-) mice are extensively used as a genetic model of several neuropsychiatric disorders, and consistently display anxiety-like behaviors and inactivity in different tests. To better understand how these mice organize their behavior, we assessed the open field and elevated plus maze spatiotemporal patterning of activity in adult male SERT wild type (+/+), heterozygous (+/-) and -/- mice on C57BL/6J genetic background using new videotracking and analytic procedures. In addition, we analyzed their spatial memory, assessing within- and between-trial habituation, and examined specific motor characteristics of their movement in these two tests. In the open field test, SERT-/- mice showed reduced vertical exploration throughout the arena, reduced central (but not peripheral) horizontal exploration, unaltered within-trial habituation, and slightly poorer between-trial habituation for horizontal activity. In the elevated plus maze, SERT-/- mice demonstrated anxiety-like avoidance of open arms, hypoactivity, as well as unaltered within-trial and between-trial habituation (except for poorer between-trial habituation of total horizontal activity). In both tests, SERT-/- mice showed greater prevalence of horizontal over vertical dimension of their exploration in the areas protected by the walls (open field periphery, plus maze closed arms), but not in open aversive areas, such as the center of the open field or center or open arms of the maze. In both arenas, SERT-/- mice consistently displayed increased turning behavior, potentially representing a perseverance-like phenotype or aberrant spatial strategies in novel environments. Overall, using a fine-graded behavioral analysis in two different novelty tests, this study revealed alterations in motor and spatiotemporal patterning of activity in SERT-/- mice. Given the relevance of exploratory strategies to human personality traits and brain disorders, our data may be useful for developing further neurobehavioral models using these mice.

摘要

血清素转运体基因敲除(SERT-/-)小鼠被广泛用作多种神经精神疾病的遗传模型,并且在不同测试中始终表现出焦虑样行为和活动减少。为了更好地理解这些小鼠如何组织其行为,我们使用新的视频跟踪和分析程序,评估了成年雄性C57BL/6J遗传背景的SERT野生型(+/+)、杂合子(+/-)和-/-小鼠在旷场和高架十字迷宫中的活动时空模式。此外,我们分析了它们的空间记忆,评估了试验内和试验间的习惯化,并检查了它们在这两项测试中运动的特定运动特征。在旷场试验中,SERT-/-小鼠在整个场地的垂直探索减少,中央(而非周边)水平探索减少,试验内习惯化未改变,水平活动的试验间习惯化略差。在高架十字迷宫中,SERT-/-小鼠表现出类似焦虑的对开放臂的回避、活动减退,以及试验内和试验间习惯化未改变(除了总水平活动的试验间习惯化较差)。在两项测试中,SERT-/-小鼠在由墙壁保护的区域(旷场周边、十字迷宫封闭臂)中,水平探索维度相对于垂直维度的占比更高,但在开放厌恶区域,如旷场中心或迷宫的中心或开放臂中并非如此。在两个场地中,SERT-/-小鼠始终表现出增加的转弯行为,这可能代表了在新环境中的一种坚持样表型或异常空间策略。总体而言,通过在两项不同的新奇性测试中进行精细分级的行为分析,本研究揭示了SERT-/-小鼠活动的运动和时空模式的改变。鉴于探索策略与人类人格特质和脑部疾病的相关性,我们的数据可能有助于利用这些小鼠开发进一步的神经行为模型。

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