Hippocampal LTP and memory in mouse strains: Is there evidence for a causal relationship?
Hippocampal LTP and memory in mouse strains: Is there evidence for a causal relationship?
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DOI：
10.1002/hipo.10101
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发表时间：
2002-01-01
期刊：
影响因子：
3.5
通讯作者：
Gerlai, R
中科院分区：
文献类型：
--
作者：
Gerlai, R
记忆背后的机制正在深入研究中。细胞水平上最有希望的候选者之一是长时程增强（LTP）。许多药理学和分子遗传操作已经导致 LTP 和记忆的改变。然而，这些表型变化之间的因果关系存在争议。因果关系问题可以通过多种方式解决。一项建议是研究小鼠品系的 LTP 和记忆表现的自然变异。如果发现突触和行为现象的变化，则可以研究这些特征之间的相关性。讨论了这种方法的优点和缺点。还提供了使用四种小鼠品系的经验示例，以强调一些常见问题。提出以下论据。首先，应进行具有特殊条件特征的多种电生理学和行为范式，以避免由于与记忆及其机制无关的改变而导致假阳性结果。多种刺激和记忆方案也可以让人们研究过程的复杂性和多样性。其次，可能需要对大量小鼠品系进行分析，以避免由于虚假基因关联和/或连锁不平衡而对结果进行错误解释。第三，使用例如双等位基因杂交的定量遗传分析可用于正确研究生物学上有意义的效应，即遗传效应。结论是，通过使用提供聚合证据的其他方法（例如 QTL 分析、基因表达阵列和生化分析），对小鼠品系的分析将有助于解决有关 UP 在记忆中可能发挥的作用的问题。 (C) 2002 Wiley-Liss, Inc.
The mechanisms underlying memory are under intense investigation. One of the most promising candidates at the cellular level is long-term potentiation (LTP). Numerous pharmacological and molecular genetic manipulations have led to alteration in both LTP and memory. However, the causal relationship between these phenotypical changes is debated. The problem of causality can be addressed in numerous ways. One suggestion is to investigate natural variation in both LTP and memory performance in mouse strains. If variation in synaptic and behavioral phenomena is found, correlation between these traits may be investigated. The advantages and disadvantages of this approach are discussed. An empirical example using four mouse strains is also presented to highlight some general problems. The following arguments are made. First, multiple electrophysiological and behavioral paradigms with idiosyncratic condition characteristics should be conducted to avoid false-positive findings due to alterations unrelated to memory and its mechanisms. Multiple stimulation and memory protocols may also allow one to study the complexity and multiplicity of processes. Second, analysis of a large number of mouse strains may be needed to avoid false interpretation of results due to spurious gene associations and/or linkage disequilibrium. Third, quantitative genetic analysis using, for example, diallele crosses, may be employed to properly investigate biologically meaningful, i.e., genetic, effects. It is concluded that with the use of additional methods (e.g., QTL analysis, gene expression arrays, and biochemical analysis) providing converging evidence, analysis of mouse strains will be instrumental in addressing the question regarding the role UP may play in memory. (C) 2002 Wiley-Liss, Inc.