Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109-2200, USA.
J Neurophysiol. 2011 Sep;106(3):1570-80. doi: 10.1152/jn.00257.2011. Epub 2011 Jun 22.
As the use of genetically engineered mice has become increasingly prevalent in neurobiological research, evidence has steadily accumulated that substantial differences exist between strains. Although a number of studies have reported effects of genetic background on behavior, few have focused on differences in neurophysiology. The postburst afterhyperpolarization (AHP) is an important determinant of intrinsic neuronal excitability and has been suggested to play a critical role in the cellular mechanisms underlying learning and memory. Using whole cell current-clamp recordings of CA1 pyramidal neurons, we examined the magnitude of different phases of the AHP (peak, medium, and slow) in two commonly used genetic backgrounds, C57BL/6 (B6) and 129SvEv (129), as well as in an F2 hybrid B6:129 background (F2). We found that neurons from B6 and F2 animals exhibited a significantly larger AHP compared with 129 animals and that this difference was consistent across all phases. Furthermore, our recordings revealed a marked dichotomy in the shape of the AHP waveform, which was independent of genetic background. Approximately 60% of cells exhibited an AHP with a sharp transition between the peak AHP and medium AHP, whereas the remaining 40% exhibited a more gradual transition. Our data add to the growing body of work suggesting that genetic background can affect neuronal function as well as behavior. In addition, these results highlight the innate heterogeneity of CA1 pyramidal neurons, even within a single genetic background. These differences should be taken into consideration during the analysis and comparison of experimental results.
随着基因工程小鼠在神经生物学研究中的应用日益广泛，越来越多的证据表明不同品系之间存在显著差异。尽管有许多研究报告了遗传背景对行为的影响，但很少有研究关注神经生理学的差异。爆发后超极化（AHP）是神经元固有兴奋性的重要决定因素，被认为在学习和记忆的细胞机制中发挥着关键作用。我们使用 CA1 锥体神经元的全细胞膜片钳记录，研究了两种常用遗传背景（C57BL/6（B6）和 129SvEv（129））以及 F2 杂交 B6:129 背景（F2）中 AHP 的不同阶段（峰值、中值和慢值）的幅度。我们发现 B6 和 F2 动物的神经元与 129 动物的神经元相比表现出明显更大的 AHP，而且这种差异在所有阶段都是一致的。此外，我们的记录揭示了 AHP 波形形状的明显二分法，这与遗传背景无关。大约 60%的细胞表现出 AHP，其中峰值 AHP 和中值 AHP 之间有明显的转变，而其余 40%的细胞则表现出更渐进的转变。我们的数据增加了越来越多的工作表明遗传背景可以影响神经元功能以及行为。此外，这些结果突出了 CA1 锥体神经元的固有异质性，即使在单一遗传背景下也是如此。在分析和比较实验结果时，应考虑这些差异。
