Fitzpatrick C M, Caballero-Puntiverio M, Gether U, Habekost T, Bundesen C, Vangkilde S, Woldbye D P D, Andreasen J T, Petersen A
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
Psychopharmacology (Berl). 2017 Mar;234(5):845-855. doi: 10.1007/s00213-016-4520-6. Epub 2017 Jan 9.
The 5-choice serial reaction time task (5-CSRTT) is widely used to measure rodent attentional functions. In humans, many attention studies in healthy and clinical populations have used testing based on Bundesen's Theory of Visual Attention (TVA) to estimate visual processing speeds and other parameters of attentional capacity.
We aimed to bridge these research fields by modifying the 5-CSRTT's design and by mathematically modelling data to derive attentional parameters analogous to human TVA-based measures.
C57BL/6 mice were tested in two 1-h sessions on consecutive days with a version of the 5-CSRTT where stimulus duration (SD) probe length was varied based on information from previous TVA studies. Thereafter, a scopolamine hydrobromide (HBr; 0.125 or 0.25 mg/kg) pharmacological challenge was undertaken, using a Latin square design. Mean score values were modelled using a new three-parameter version of TVA to obtain estimates of visual processing speeds, visual thresholds and motor response baselines in each mouse.
The parameter estimates for each animal were reliable across sessions, showing that the data were stable enough to support analysis on an individual level. Scopolamine HBr dose-dependently reduced 5-CSRTT attentional performance while also increasing reward collection latency at the highest dose. Upon TVA modelling, scopolamine HBr significantly reduced visual processing speed at both doses, while having less pronounced effects on visual thresholds and motor response baselines.
This study shows for the first time how 5-CSRTT performance in mice can be mathematically modelled to yield estimates of attentional capacity that are directly comparable to estimates from human studies.
五选择连续反应时任务(5-CSRTT)被广泛用于测量啮齿动物的注意力功能。在人类中,许多针对健康人群和临床人群的注意力研究都采用了基于布伦森视觉注意理论(TVA)的测试,以估计视觉处理速度和注意力容量的其他参数。
我们旨在通过修改5-CSRTT的设计并对数据进行数学建模,以得出与基于人类TVA的测量方法类似的注意力参数,从而将这些研究领域联系起来。
连续两天对C57BL/6小鼠进行两次为时1小时的5-CSRTT测试,该测试版本中刺激持续时间(SD)探测长度根据先前TVA研究的信息而变化。此后,采用拉丁方设计进行氢溴酸东莨菪碱(0.125或0.25mg/kg)药理学挑战。使用TVA的新三参数版本对平均得分值进行建模,以获得每只小鼠的视觉处理速度、视觉阈值和运动反应基线的估计值。
每只动物的参数估计在各测试阶段均可靠,表明数据足够稳定,足以支持个体水平的分析。氢溴酸东莨菪碱剂量依赖性地降低了5-CSRTT的注意力表现,同时在最高剂量时还增加了奖励获取潜伏期。在TVA建模中,氢溴酸东莨菪碱在两种剂量下均显著降低了视觉处理速度,而对视觉阈值和运动反应基线的影响较小。
本研究首次表明,小鼠的5-CSRTT表现如何通过数学建模得出注意力容量的估计值,这些估计值可直接与人类研究的估计值进行比较。