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「干货分享」:触屏操作性行为系统范式任务解读

更新时间  2022-11-09 22:40 阅读
本文摘要:泉源:瑞沃德生命科学执行功效可以被观点化为一组协调其他认知和行为的历程或机制。执行功效通常被形貌为可以被选择、更新和计划的运动历程,克制和停止相关的行为,在适当情况下被监测和改变的行为,疏散、转换和保持注意力等一系列历程的荟萃。这些历程可能具有重复的特征和机制,同时也代表着差别的心理结构。 这种历程的中断与种种精神和神经紊乱有关,而且有相当多的证据讲明执行功效(至少部门)依赖于额叶的功效完整性。因此建设可靠、有效、可转化的动物执行功效评估任务变得尤为重要。

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泉源:瑞沃德生命科学执行功效可以被观点化为一组协调其他认知和行为的历程或机制。执行功效通常被形貌为可以被选择、更新和计划的运动历程,克制和停止相关的行为,在适当情况下被监测和改变的行为,疏散、转换和保持注意力等一系列历程的荟萃。这些历程可能具有重复的特征和机制,同时也代表着差别的心理结构。

这种历程的中断与种种精神和神经紊乱有关,而且有相当多的证据讲明执行功效(至少部门)依赖于额叶的功效完整性。因此建设可靠、有效、可转化的动物执行功效评估任务变得尤为重要。小编今天带你探讨本文献中,三种使用啮齿类触屏操作性行为系统,举行评估执行功效的实验范式任务,这三种实验任务已被多种动物模型验证有效。

前期训练:这三个实验任务都是基于动物对触屏刺激举行反映以获得食物奖励而驱动的,举行前期训练的目的,是让动物学习适当的触屏行为,在举行训练之前,Stage1需要对动物举行饮食控制,Stage2-5如图所示:Figure 1 | Flowchart overview of pretraining stages 2–5. Stage 2: a visual stimulus is presented in one of the response windows. If it is not touched, stimulus offset occurs after 30 s and a reward is delivered. If it is touched, offset is immediate and a triple reward is delivered. After reward collection and an ITI period, the next stimulus is presented in a new trial. Stage 3 proceeds as in stage 2, but the stimulus remains on the touchscreen until touched. Animals to be tested on extinction can proceed directly to the extinction procedure after reaching criterion on stage 3. Stage 4 proceeds as in stage 3, but the animal must enter and exit the magazine after the ITI to initiate the next trial. Stage 5 proceeds as in stage 4, but touches to blank response windows (when there is a stimulus on the screen) are discouraged with a time out. After this and the ITI, the next trial may be initiated, but in pretraining for the majority of tasks this is a CT in which the previous stimulus is represented, rather than a new trial. Note that CTs are not given in stage 5 of pretraining for the 5-CSRT. The labels in italics indicate steps in which the animal is required to perform an action.消退任务(Extinction)——一种对先前奖励的习得反映的抑制率和忘却水平的分析任务。学会停止做出不再能提供期望或相适应效果的反映的能力,与前期学会通过适当反映获得期望的夸奖一样重要。

人们早期就意识到消退现象是一种庞大的机制,不仅仅与前期的学习、遗忘相关,也与情景信息高度相关。大量文献使用条件恐惧举行消退研究,但对消退相关的神经机制研究甚少。在触屏操作性行为系统的消退任务中,首先训练动物对一个简朴的视觉刺激举行的反映(例如,触摸一个白色的正方形),以获得奖励。

通过习得阶段之后,动物对相同的视觉刺激举行反映却不再获得奖励,动物抑制自己对视觉刺激举行反映所需的时间和水平,代表了其学习能力消退情况。动物执行消退任务的体现受多种因素和机制影响,如小鼠品系、基因突变等,差别品系的实验动物对消退任务的体现差别,相对于DBA/2J小鼠,C57BL/6J 小鼠和BALB/cJ 小鼠在触屏操作性行为系统消退任务的数据体现更好。基因突变也是影响动物消退任务体现的因素,谷氨酸受体亚型AMPA GluA1基因的缺失,NMDA受体亚基GluN2A基因编码的缺失会削弱动物的消退能力。

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与此同时,视觉刺激的多样性和灵活性使得消退任务成为研究消退神经机制的创新性和拓展性实验方法。Figure 2 | Extinction task. (a) Schematic of a three-hole mask used in the extinction paradigm. (b) Flowchart overview of acquisition learning phase. After initiation, a solid white square stimulus is presented at a central location on the touchscreen. When the subject touches the stimulus, a reward is delivered, and after reward collection and an ITI, a new trial may be initiated. The labels in italics indicate steps in which the animal is required to perform an action. (c) Flowchart overview of extinction learning phase. Each trial begins with a 10-s ITI, after which the single, solid white square stimulus is presented on the touchscreen. The subject is not required to initiate the trial. If the subject either touches the stimulus (response) or does not touch the stimulus within a 10-s duration (omission), the stimulus is removed and the 10-s ITI leading to the next trial is initiated. No rewards or conditioned reinforcers (e.g., tray light or tone associated with reward delivery) are delivered during the extinction phase. The labels in italics indicate steps in which the animal is required to perform an action. (d) Representative data of C57BL/6J mice using a two-choice acquisition and extinction procedure, showing the typical number of sessions to criterion (data re-plotted from ref. 45). (e) Representative data from the same mice showing the time course of response extinction. Data are presented as means ± s.e.m.反转学习任务(Reversal Learning)——对以前没有奖励但之后会有奖励的视觉刺激(与之前有奖励但之后不再有奖励的视觉刺激)作出调整反映的速度和水平举行评估测试的任务。除消退学习之外,生物体需要能够凭据情况变化和规则变化灵活调整自身的行为,反转学习任务被广泛地用于该行为灵活性的评估分析。

在反转学习任务中,被试首先会学习区分有奖励和无奖励的视觉刺激,并对有奖励的视觉刺激举行反映以获得夸奖,通过差别视觉刺激的学习之后,对视觉刺激的夸奖举行转换,被试不仅需要区分视觉刺激,还要学会区分之前给与夸奖的视觉刺激不再举行夸奖,并对前期没有夸奖、而现在会有夸奖的视觉刺激举行反映;被试学会并调整自己行为的数据指标(如所需时长、正确率等)以示被试的反转学习的灵活性能力。精神破裂症、帕金森、强迫症等多种精神性疾病患者的反转学习能力均泛起异常,文献证据讲明反转学习任务的功效性神经环路包罗PFC(尤其是眶额皮质)——腹侧纹状体,同时也与神经递质血清素(5-HT)和多巴胺信号通路相关。啮齿类动物的触屏反转学习任务研究也发现与甲基苯丙胺、D1受体、NMDA受体亚基GluN2A、AMPA受体亚基GluA1等相关。触屏反转学习任务的高度敏捷性特征使该任务范式成为神经机制和环路研究的重要创新性和灵活性的研究方法。

Figure 3 | Reversal learning task. (a) Schematic of a two-window mask and stimuli used in the reversal learning paradigm. (b) Flowchart overview of the reversal learning procedure. After initiation, a pair of stimuli (CS + , CS − ) is presented on the screen, in pseudorandom locations. Correct responses (to CS + ) are rewarded, and after reward collection and an ITI, a new trial may be initiated. Incorrect responses (to CS − ) are discouraged with a time out, and then after an ITI and initiation the previous trial type is represented (a correction trial). The correction trial loop will continue until a correct response is made. The labels in italics indicate steps in which the animal is required to perform an action. (c) Spider versus plane stimuli typically used for visual discrimination and reversal learning in rats. (d) Horizontal versus vertical pattern stimuli, which rats acquire more readily. (e) Typical reversal learning performance in rats (n = 10, with a history of object-location paired associates learning and trial-unique nonmatching-to-location training) using ‘castle’ versus ‘face’ photographic stimuli (C.A.O., unpublished data). (f) Typical reversal learning performance in mice (n = 17, of mixed background (~1:15 /ca:C57BL/6J), using ‘marble’ versus ‘fan’ stimuli (A.E.H., unpublished data). Data are presented as means ± s.e.m5-选择反映序列时任务(the 5-CSRT task)——对短暂出现的、空间不行预测的视觉刺激有选择性地探测并作出适当反映能力的评估测试任务。5-CSRT任务训练啮齿动物对水平排列5个空间位置随机泛起的视觉刺激举行分辨, 该任务可用于评估执行功效的多个方面:反映正确率(在所有实验试验中正确的比例)意味着连续的、空间的注意力的丈量评估;遗漏次数是注意历程的指标参数;过早反映(刺激开始前的反映)或连续反映(夸奖反馈后的分外反映)是抑制控制的指标参数,划分与激动性和强迫性有关;与此同时,动物对夸奖的反映时间和延迟与肌肉运念头能、念头因素等相关;这些数据指标对动物认知具有高度敏捷的探测能力,3×TgAD 和TgCRND8 AD模型小鼠在5-CSRT任务中的正确率显著低于正常小鼠;相对于C57Bl/6J 小鼠,自闭症模型小鼠BTBR T + tf/J 对短时刺激反映的正确率显著降低,同时激动增加、念头淘汰. 此实验任务对于刺激的灵活性和实验的敏感性具有较高要求的认知研究是极有资助的。Figure 4 | 5-CSRT task. (a) Schematic of a five-hole mask used in the 5-CSRT paradigm. (b) Flowchart overview of the 5-CSRT task. A trial is initiated when the subject enters and withdraws its head from the illuminated magazine. After a 5-s delay, a white square stimulus is briefly presented in one of the five response windows. Touching the white-square location either when the stimulus is present or during a short subsequent limited-hold period is recorded as a correct trial and rewarded. Collection of reward initiates a 5-s ITI. A response in any other response window is recorded as an incorrect trial and results in a time-out period, before the beginning of the 5-s ITI. Failure to respond at the screen during the stimulus presentation or the limited-hold period is recorded as an omission and also leads to a time out. Response(s) before the onset of the stimulus is recorded as a premature response, and lead to a time out, but premature trials do not contribute to the session trial count. After the ITI has elapsed, the magazine is illuminated and the subject can initiate another trial. (c,d) Representative data illustrating the dependence of response accuracy and omission, respectively, on stimulus duration in adult C57Bl/6J mice (S.R.O.N., L.M.S. and T.J.B., unpublished data). Data are means ± s.e.m.这么优秀的实验任务,究竟该怎么做? Nature Protocals文献里先容了,举行以上三个实验范式的行为学设备——触屏操作性行为系统,点击相识详情!Figure 5 | Annotated photographs of a Campden Instruments rat touchscreen chamber. (1) Touchscreen, (2) black plastic mask covering touchscreen except for response windows, (3) black Perspex walls, (4) pellet dispenser, (5) IR beam assembly, (6) house light positioned above the chamber, (7) IR camera positioned above the chamber, (8) tone and click generator and (9) a sound/light-attenuating box with a ventilation fan fitted.参考文献:1.Mar, A. C., Horner, A. E., Nilsson, S. R., Alsiö, J., Kent, B. A., Kim, C. H., ... & Bussey, T. J.. 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