Strain-dependent differences in LTP and hippocampus-dependent memory in inbred mice

Strain-dependent differences in LTP and hippocampus-dependent memory in inbred mice
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DOI:
10.1101/lm.7.3.170
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发表时间:
2000-05-01
期刊:
影响因子:
2
通讯作者:
Bourtchouladze, R
Bourtchouladze, R
中科院分区:
医学4区
文献类型:
--
作者:
Nguyen, PV;Abel, T;Bourtchouladze, R

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许多研究已经利用“反向”遗传学产生了“基因敲除”和转基因小鼠,以探索各种分子在长时程增强(LTP)和空间记忆中的作用。各种近交系小鼠的存在为探索学习和记忆的遗传基础提供了另一种方法。我们检测了C57BL/6J、CBA/J、DBA/2J和129/SvEms-+(Ter?)/J四个近交系小鼠的行为记忆和CA1区LTP的表达。结果发现,在C57BL/6J和DBA/2J小鼠中,由四个100 Hz序列刺激诱导的LTP是健壮和持久的,而在CBA/J和129/SvEms-+(Ter?)/J小鼠中,LTP的表达衰退。1小时后,129/SvEms-+(Ter?)/J小鼠的LTP明显小于其他3个品系。CBA/J、DBA/2J和129/SvEms-+(Ter?)/J小鼠的Theta-Burst LTP持续时间比C57BL/6J小鼠短。在海马体依赖记忆的空间和非空间测试中,我们还观察到了特定小鼠品系之间的特定记忆缺陷。CBA/J小鼠在Morris水迷宫中表现出学习障碍,DBA/2J和CBA/J品系在情景和线索恐惧条件反射实验中均表现出缺乏长期记忆。我们的发现为某些形式的突触可塑性提供了强有力的遗传基础,这些突触可塑性与行为长期记忆有关,并表明遗传背景可以影响在转基因小鼠中观察到的电生理和行为表型,这些转基因小鼠阐明了学习、记忆和LTP的分子基础。
Many studies have used "reverse" genetics to produce "knock-out" and transgenic mice to explore the roles of various molecules in long-term potentiation LTP) and spatial memory. The existence of a variety of inbred strains of mice provides an additional way of exploring the genetic bases of learning and memory. We examined behavioral memory and LTP expression in area CA1 of hippocampal slices prepared from four different inbred strains of mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms-+(Ter?)/J. We found that LTP induced by four 100-Hz trains of stimulation was robust and long-lasting in C57BL/6J and DBA/2J mice but decayed in CBA/J and 129/SvEms-+(Ter?)/J mice. LTP induced by one 100-Hz train was significantly smaller after I hr in the 129/SvEms-+(Ter?)/J mice than in the other three strains. Theta-burst LTP was shorter lasting in CBA/J, DBA/2J, and 129/SvEms-+(Ter?)/J mice than in C57BL/6J mice. We also observed specific memory deficits, among particular mouse strains, in spatial and nonspatial tests of hippocampus-dependent memory. CBA/J mice showed defective learning in the Morris water maze, and both DBA/2J and CBA/J strains displayed deficient long-term memory in contextual and cued fear conditioning tests. Our findings provide strong support for a genetic basis for some forms of synaptic plasticity that are linked to behavioral long-term memory and suggest that genetic background can influence the electrophysiological and behavioral phenotypes observed in genetically modified mice generated fur elucidating the molecular bases of learning, memory, and LTP.