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一种自动量化精神兴奋剂诱发的路径追踪刻板行为的新方法:应用于小家鼠。

A novel method for automatic quantification of psychostimulant-evoked route-tracing stereotypy: application to Mus musculus.

作者信息

Bonasera Stephen J, Schenk A Katrin, Luxenberg Evan J, Tecott Laurence H

机构信息

Division of Geriatrics, Department of Medicine, University of California, San Francisco, 1550 4th St., Box 2822, San Francisco, CA 94158-2822, USA.

出版信息

Psychopharmacology (Berl). 2008 Mar;196(4):591-602. doi: 10.1007/s00213-007-0994-6. Epub 2007 Dec 21.

Abstract

RATIONALE

Route-tracing stereotypy is a powerful behavioral correlate of striatal function that is difficult to quantify. Measurements of route-tracing stereotypy in an automated, high throughput, easily quantified, and replicable manner would facilitate functional studies of this central nervous system region.

OBJECTIVE

We examined how t-pattern sequential analysis (Magnusson Behav Res Meth Instrum Comput 32:93-110, 2000) can be used to quantify mouse route-tracing stereotypies. This method reveals patterns by testing whether particular sequences of defined states occur within a specific time interval at a probability greater than chance.

RESULTS

Mouse home-cage locomotor patterns were recorded after psychostimulant administration (GBR 12909, 0, 3, 10, and 30 mg/kg; d-amphetamine, 0, 2.5, 5, and 10 mg/kg). After treatment with GBR 12909, dose-dependent increases in the number of found patterns and overall pattern length and depth were observed. Similar findings were seen after treatment with d-amphetamine up to the dosage where focused stereotypies dominated behavioral response. For both psychostimulants, detected patterns displayed similar morphological features. Pattern sets containing a few frequently repeated patterns of greater length/depth accounted for a greater percentage of overall trial duration in a dose-dependant manner. This finding led to the development of a t-pattern-derived route-tracing stereotypy score. Compared to scores derived by manual observation, these t-pattern-derived route-tracing stereotypy scores yielded similar results with less within-group variability. These findings remained similar after reanalysis with removal of patterns unmatched after human scoring and after normalization of locomotor speeds at low and high ranges.

CONCLUSIONS

T-pattern analysis is a versatile and robust pattern detection and quantification algorithm that complements currently available observational phenotyping methods.

摘要

原理

路径追踪刻板行为是纹状体功能的一种强大行为关联,难以量化。以自动化、高通量、易于量化且可重复的方式测量路径追踪刻板行为将有助于对该中枢神经系统区域进行功能研究。

目的

我们研究了t模式序列分析(Magnusson Behav Res Meth Instrum Comput 32:93 - 110, 2000)如何用于量化小鼠路径追踪刻板行为。该方法通过测试特定定义状态序列在特定时间间隔内出现的概率是否大于随机概率来揭示模式。

结果

在给予精神兴奋剂(GBR 12909,0、3、10和30 mg/kg;d - 苯丙胺,0、2.5、5和10 mg/kg)后记录小鼠笼内运动模式。用GBR 12909处理后,观察到发现的模式数量、总体模式长度和深度呈剂量依赖性增加。在用d - 苯丙胺处理后,直至聚焦刻板行为主导行为反应的剂量,也观察到类似结果。对于两种精神兴奋剂,检测到的模式显示出相似的形态特征。包含一些长度/深度较大且频繁重复模式的模式集以剂量依赖方式在总体试验持续时间中占更大比例。这一发现促成了基于t模式的路径追踪刻板行为评分的开发。与通过人工观察得出的评分相比,这些基于t模式的路径追踪刻板行为评分产生了相似的结果,且组内变异性更小。在去除人工评分后不匹配的模式并对低范围和高范围运动速度进行归一化重新分析后,这些结果仍然相似。

结论

t模式分析是一种通用且强大的模式检测和量化算法,可补充当前可用的观察表型分析方法。

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