Buhusi Catalin V, Meyer Abby E, Oprisan Sorinel A, Buhusi Mona
Neuroscience Program, Department of Psychology, Utah State University, Logan, UT.
Department of Physics and Astronomy, College of Charleston, Charleston, SC.
Timing Time Percept. 2023 Apr;11(1-4):242-262. doi: 10.1163/22134468-bja10052. Epub 2022 Jul 15.
Many species, including humans, show both accurate timing-appropriate time estimation in the seconds to minutes range-and -time estimation error varies linearly with estimated duration. Behavioral paradigms aimed at investigating interval timing are expected to evaluate these dissociable characteristics of timing. However, when evaluating interval timing in models of neuropsychiatric disease, researchers are confronted with a lack of adequate studies about the parent (background) strains, since accuracy and scalar timing have only been demonstrated for the C57Bl/6 strain of mice (Buhusi et al., 2009). We used a peak-interval procedure with three intervals-a protocol in which other species, including humans, demonstrate accurate, scalar timing-to evaluate timing accuracy and scalar timing in three strains of mice frequently used in genetic and behavioral studies: 129, Swiss-Webster, and C57Bl/6. C57Bl/6 mice showed accurate, scalar timing, while 129 and Swiss-Webster mice showed departures from accuracy and/or scalar timing. Results suggest that the genetic background / strain of the mouse is a critical variable for studies investigating interval timing in genetically-engineered mice. Our study validates the PI procedure with multiple intervals as a proper technique, and the C57Bl/6 strain as the most suitable genetic background to date for behavioral investigations of interval timing in genetically engineered mice modeling human disorders. In contrast, studies using mice in 129, Swiss-Webster, or mixed-background strains should be interpreted with caution, and thorough investigations of accuracy and scalar timing should be conducted before a less studied strain of mouse is considered for use in timing studies.
包括人类在内的许多物种都具有精确计时能力——在秒到分钟范围内能够进行适当的时间估计——并且时间估计误差与估计持续时间呈线性变化。旨在研究间隔计时的行为范式有望评估计时的这些可分离特征。然而，在评估神经精神疾病模型中的间隔计时时，研究人员面临着关于亲代（背景）品系缺乏充分研究的问题，因为只有C57Bl/6品系的小鼠被证明具有准确性和标量计时能力（布胡西等人，2009年）。我们使用了一种具有三个间隔的峰值间隔程序——一种包括人类在内的其他物种都能展示精确、标量计时的方案——来评估在遗传和行为研究中常用的三种小鼠品系（129、瑞士韦伯斯特和C57Bl/6）的计时准确性和标量计时。C57Bl/6小鼠表现出精确、标量计时，而129和瑞士韦伯斯特小鼠则表现出与准确性和/或标量计时的偏差。结果表明，小鼠的遗传背景/品系是研究基因工程小鼠间隔计时的关键变量。我们的研究验证了具有多个间隔的PI程序是一种合适的技术，以及C57Bl/6品系是迄今为止用于模拟人类疾病的基因工程小鼠间隔计时行为研究的最合适遗传背景。相比之下，使用129、瑞士韦伯斯特或混合背景品系小鼠的研究应谨慎解释，在考虑将研究较少的小鼠品系用于计时研究之前，应进行准确性和标量计时的全面调查。
