这项研究得到了澳大利亚 RMH 神经科学基金会的支持;澳大利亚大脑基金会;澳大利亚 RACP Thyne 里德奖学金;由认知科学和技术委员会的项目赠款, 伊朗对阿巴斯 Haghparast。

这里解释的所有程序都是按照《动物保育和使用指南》批准和执行的, 并经 Florey 研究所动物伦理委员会或神经科学研究中心批准。
1. 住房、搬运和食物限制
<ol><li>使用成年 (通常8周大) 雄性大鼠 (任何菌株), 并保持他们在房间内的12小时的光/暗循环。</li>
	<li>限制他们的食物接触, 鼓励动物执行任务。 注意: 建议动物的住房, 因为它提供更好的控制每一个人的食物摄入量。</li>
	<li>1-3 天, 每天处理动物大约5分钟, 2x。 注意: 处理熟悉与人类接触的动物, 并减少在整个实验动物的压力和焦虑水平。</li>
	<li>在每次处理会话后对动物进行称量。使用第一天的重量作为免费喂养量, 并保持动物约 80-85% 的免费喂养量。</li>
</ol>2. 实验设置
<ol><li>使用装有3个分区或武器的 T 迷宫、2个刺激扬声器、5个可伸缩门和5个红外运动传感器或红外光束 (IRB) 传感器。 注: T 型迷宫可由中密度纤维板 (MDF) 或聚氯乙烯 (PVC) 构成。</li>
	<li>控制在这里构造的迷宫由一个 Arduino 微控制器。</li>
	<li>将 Arduino 代码复制到计算机中。</li>
	<li>从软件网站下载 Arduino 软件并将其安装在计算机上。</li>
	<li>使用 USB 端口将微控制器连接到计算机。</li>
	<li>在 "计算机" 上, 单击 "软件" 图标, 转到 "工具", 然后选择 "端口"。</li>
	<li>从下拉菜单中, 选择将软件连接到计算机的 COM 端口 (通信端口)。</li>
	<li>转到工具并选择主板。从下拉菜单中, 选择控制 T 迷宫的 Arduino 的类型。</li>
	<li>单击 "界面" 窗口左上方的 "上载"。选择 Arduino 代码。等待进程完成。</li>
	<li>单击 "接口" 窗口右上的 "串行监视器"。然后, 在新的弹出窗口中, 将波特率更改为115200。</li>
</ol>3. 适应迷宫
<ol><li>在每一次的适应之前, 把动物带到实验室至少1小时之前的实验。</li>
	<li>在每个球门臂上留出10块糖丸, 让所有的门都开着。 注意: 在这个阶段, 没有必要跟踪动物的运动 (图 1)。</li>
	<li>天 1-3: 在迷宫中单独放置动物10分钟, 每天 1x, 探索迷宫没有限制。</li>
	<li>天 4-5: 安置动物单独地在迷宫。每只手臂留出2粒, 让他们从两边取样。将动物从迷宫中取出后, 立即从两侧或5分钟后在迷宫中进食。 注意: 这一阶段和上一阶段的主要区别是, 动物需要从迷宫中的两个球后立即被移除。这将使动物熟悉在试验结束时从迷宫中移除。</li>
	<li>每节课后, 用70% 乙醇清洁迷宫的地板, 并确保在将下一个动物放到迷宫中之前, 乙醇已经蒸发。</li>
</ol>4. 歧视培训
<ol><li>
迷宫准备
	<ol>
<li>6天: 实验前, 把动物带到实验室至少1小时。</li>
		<li>运行 Arduino 程序, 并将试验编号设置为 14, 其中前4项试验将被强制选择, 其余的将是选择试验。 注意: 该程序将随机生成相同数量的试验被分配到 T 迷宫的左和右端。</li>
		<li>在每次试验开始之前, 将4粒球放在目标臂中, 将被提示为 HRA, 另一臂是上帝抵抗军的2颗小球。</li>
	</ol>
</li>
	<li>
强迫选择试验训练 (4 项试验)
	<ol>
<li>伪随机阻断一只手臂在每次试验前使动物被迫选择另一只手臂。 注: 被阻断的手臂可以是一个高奖赏臂或低奖赏臂, 而听觉信号突出的侧面的 HRA。</li>
		<li>将动物放在 "开始" 框中 (图 1)。5-7 秒后, 同时打开启动门并在 Arduino 的界面窗口中单击 "开始"。</li>
		<li>进食小球后立即收集动物, 或在迷宫中5分钟后采集。</li>
		<li>把动物留在笼子里2分钟。</li>
	</ol>
</li>
	<li>
选择试用培训 (10 项试验)
	<ol>
<li>在每次试验之前, 关闭门 B 在胳膊被选择由软件是 HRA。离开门-在相反的手臂 (上帝抵抗军) 开放。</li>
		<li>将动物放在 "开始" 框中 (图 1)。5-7 秒后, 同时打开启动门并单击 "开始"。</li>
		<li>让动物自由选择任一臂。如果动物选择了 HRA, 打开门, 让动物进入房间, 关上门, 打开门 B 立即给动物进入选定的食物好。</li>
		<li>如果动物选择了上帝抵抗军, 打开门 B, 以使动物获得食物的良好。</li>
		<li>在吃完所选食品中的所有食物后, 将其移走, 并将其留在笼中2分钟。</li>
		<li>为每种动物完成10项选择试验, 并在每次试验中记录动物的选择 (HRA 或上帝抵抗军)。</li>
		<li>在每次训练后计算所有选择试验的高奖赏选择百分比。</li>
		<li>完成14步后, 每个红外线传感器获得的各个时间都显示在 Arduino 界面窗口中。</li>
	</ol>
</li>
</ol>5. 延迟培训
<ol><li>一旦每一个动物已经达到80% 的人权委员会在歧视训练 (步骤 4), 开始延迟训练, 每天运行10试验, 每一个动物。在这一阶段, 门 B 将被打开后, 只有5的延迟, 当动物选择 HRA。</li>
	<li>如果该动物在训练课程结束时达到80% 的人权委员会, 在5的延迟时间内, 将推迟到十年代进行下一个培训课程。</li>
	<li>一旦该动物已达到80% 的人权委员会, 十年代的延迟, 增加推迟到十五年代的下一个培训课程。</li>
	<li>记录每项试验的动物选择, 在每次训练后计算人权委员会。</li>
	<li>试验完成后, 每个红外线传感器所获得的各个时间都显示在 Arduino 界面窗口中。 注 1: 单击Enter时计时器开始。"Time_decision" 是鼻子戳到 IRB-1 的时间。"Time_left_1" 是动物打破 IRB-1L 和 ' Time_left_2 ' 的时候, IRB-2L 被打破了。如果将行为研究与电生理学或神经成像 (如钙成像) 方法结合起来, 则建议用胶片记录更好地将动物的行为与神经信号同步。</li>
</ol>6. 电生理学 (电极制造)
<ol><li>使用单极或双极性电极记录局部磁场电位 (LFPs)。 注意: 建议使用双极性电极, 因为它能使局部重新参照, 以减少体积传导的影响。因此, 记录的 LFP 是2电极之间的差电压与200微米距离之间的提示。</li>
	<li>要制造两极电极, 请将2个钨电极粘合在一起, 或将2不锈钢线连接在一起 (通常, 使用50微米直径的粉煤灰涂层不锈钢线)。</li>
	<li>将接地和记录线焊接到迷你插头/插座上, 成为电生理记录系统的连接器。</li>
</ol>7. 麻醉
<ol><li>要植入电极, 麻醉大鼠腹腔注射氯胺酮 (100 毫克/千克) 和甲苯噻嗪 (8 毫克/千克) 混合物, 或管理异氟醚, 如以下步骤所述。 注意: 建议使用异氟醚, 因为它的麻醉深度控制得到改善。</li>
	<li>使用有控制氧和麻醉蒸汽流的麻醉机。</li>
	<li>用异氟醚麻醉动物, 将其放置在感应腔内, 在麻醉机上将异氟醚设置为大约4% 和 500-1000 毫升/分钟的氧气。</li>
	<li>继续诱导直到动物的矫正反射消失。</li>
	<li>在机器上设置 1-2.5% 异氟醚和 300-400 毫升/分氧的麻醉维持率。</li>
	<li>将隔热垫 (棉绒) 放在立体定向装置上, 然后将该动物固定在立体定向装置中。</li>
	<li>通过捏动物的脚趾来测量麻醉的水平。</li>
</ol>8. 手术方法
<ol><li>使用电动剃须刀或剪刀, 剃掉动物的头部, 在切口是要作出。</li>
	<li>用乙醇擦洗手术区, 然后用 povidone–iodine, 4%。</li>
	<li>在手术中应用眼部润滑剂保护动物的角膜。</li>
	<li>使用纸巾钳, 轻轻地拉在动物的眼睛和耳朵之间的皮肤。使用剪刀, 切断钳夹之间的皮肤, 取出骨膜。</li>
	<li>使用过氧化氢清洁和消毒头骨。</li>
	<li>使用立体定位坐标找到电极插入点的位置, 并在头骨上标记一个永久性标记。</li>
	<li>使用手持钻头为接地电极制造一个孔, 一个用于锚固植入物, 每个记录电极上有一个孔。</li>
	<li>插入电极以非常缓慢的速度, 以尽量减少可能的皮质和皮层下的损害。</li>
	<li>用小螺丝将接地电极连接到头骨上。</li>
	<li>使用薄层的牙科丙烯酸水泥, 确保连接器插头/插座到位。</li>
	<li>注射丁丙诺啡 (15 µg/千克, 皮下) 或 meloxicam (1-3 毫克/千克, 皮下) 作为止痛药。</li>
	<li>把动物留在一个温暖的垫子上的笼子里恢复。至少每30分钟观察一次动物, 直到它从麻醉剂中恢复。</li>
</ol>9. 程序后培训
<ol><li>手术后, 至少允许10天的恢复期。将动物单独带到食物和水的广告随意并每天监视它们 (参见 Rudebeck、沃尔顿、史密斯、班诺曼和拉什沃思7 , 了解更多信息)。</li>
	<li>在恢复之后, 开始将动物的饮食限制在免费喂养量的85%。</li>
	<li>重新培训迷宫中的动物, 以召回歧视阶段 (步骤 4)。</li>
	<li>继续对老鼠进行重新训练, 直到他们达到80% 的人权委员会。</li>
</ol>

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作者没有什么可透露的。

啮齿目动物长期被使用了在处理不同的题目的神经科学研究研究, 从认知能力例如学习和记忆2,14和增强的行为7,15,16对器官的中央控制17,18和神经药理学19,20。拟议的议定书解释了一个复杂的行为任务, 适合的实验涉及电生理和神经影像学。我们描述了大鼠延迟基强化导引任务, 但它可以适应小鼠, 因为大鼠和小鼠执行类似的干土地任务。
我们用鼻子戳作为刺激来触发音频刺激。然而, 杠杆压制和其他刺激方式, 如视觉或嗅觉刺激也可以单独或同时使用。拟议的操作任务比现有的非操作性方法有许多好处和优势。最引人注目的是对动物的决定过程的自动精确戳, 否则, 是非常困难的。该方法特别适合于电生理和神经影像学研究。另一个优点是删除需要空间内存控制组的任务的空间组件。作为一个高度苛刻的任务, 很可能不是所有的老鼠表现良好的范式。如果动物在启动臂中保持闲置状态, 请更换它, 延迟进入决策区超过5分钟或产生更高的错误率与组中的其他动物比较。
在任何决策时刻, 假定任何选择的成本和价值都将同时进行评估。因此, 在这项任务中选择 HRA 或上帝抵抗军, 可能是成本编码、收益编码或成本效益计算中的变化的结果。建议的方法的一个告诫是无法区分编码过程。
在训练动物和记录他们的电生理信号的过程中, 可以采取一些步骤来获得最大的成功。首先, 在训练前处理动物是至关重要的。当录音会话开始时, 将录音导线连接到动物的头部, 试着使它们适应, 让你保持头部。这是非常重要的, 因为不经常被处理的动物在这个过程中变得焦虑, 可能损坏头阶段或录音缆绳。一般来说, 处理得当的动物的压力较小, 易于使用, 而且往往产生较少的可变数据。
其次, 啮齿类动物在迷宫中留下了各种各样的气味线索 (即含有信息素的尿液和粪便, 从它们的晶须区域分泌费洛蒙, 以及从脚垫中排出的液体)。因此, 迷宫需要在每一个人使用后被抹去, 并在实验结束时将这些残留气味分子对测试结果的影响降到最低。乙醇 (70%) 是用于清洁检测设备的常用消毒剂。然而, 与许多消毒剂一样, 酒精本身也有一种气味, 可以影响啮齿动物的行为。因此, 在把动物放进迷宫之前, 要确保它已经完全蒸发了。
第三, 虽然 LFPs 对噪声的敏感度比峰值低, 但使用固体连接器和安全的电缆可以降低移动噪声的水平。在迷宫地板上轻轻喷洒水, 可以减少动物皮毛与地面之间的摩擦力所产生的静电。
最后, 本文所描述的协议可以帮助设计基于延迟的增强决策实验, 并在动物执行任务时记录电生理信号。

决策是根据决策者的价值和偏好以及所选行动1的后果来识别和选择选择的过程。尽管决策在不同领域 (即经济学、心理学和神经科学) 中得到了广泛的研究, 但这种认知能力背后的神经机制尚未得到充分的理解。决策的两个子类是感性决策和增强导向决策。虽然它们包含相当多的重叠元素和概念, 感性决策依赖于现有的感官信息1,2, 而加强导向决策处理相对价值在特定时间刻度3中获得的操作。增强决策的一个重要方面是成本效益分析, 它是通过计算给定选择的好处并减去每种备选方案1的相关成本而直观地执行的。
T 迷宫 (或变种 Y 迷宫) 是使用啮齿动物的认知实验中使用最广泛的迷宫之一。动物被放置在起始臂 (T 的底部), 并允许选择目标臂 (其中一个侧臂)。任务, 如强迫交替或左-右歧视主要是用来与啮齿类动物在 T 迷宫测试参考和工作记忆4。T 迷宫也广泛用于决策实验5,6,7。在最简单的设计中, 奖励只放在一个目标臂上。这种选择是可以预测的, 而无论奖励价值如何, 动物们肯定更喜欢奖赏而不是一无所有。另一种选择是在两个目标武器中放置奖励, 然后让动物根据几个参数 (即动物的自然喜好、奖励的价值和支付的费用) 选择哪条路径。在基于价值的设计中, 由于具有称量尺度属性, 任务更加复杂。这样, 动物通过在两种替代品之间选择, 以及在行动的成本 (即等待的量 (延迟) 或获得奖励所需的努力 (基于努力的工作量) 之间, 得到不同的价值奖赏,每个作出贡献的决定,5,6。
在传统的基于延迟的 T 迷宫决策中, 动物被训练来选择高奖赏臂 (HRA), 避免相反的低奖赏臂 (上帝军)。在整个实验中, HRA 和上帝抵抗军的两侧保持不变。尽管上述任务在文献中有很好的记载, 但它还是有几个程序上的弊端。首先, 通过有一个固定的目标手臂, 动物知道哪一个手臂选择从一开始的试验。在这种情况下, 动物可以根据记忆而不是决策来选择目标臂。因此, 在一个基于延迟的决策范式中, 如果动物因为研究干预而选择了低报酬, 就不清楚这是由于记忆力的丧失还是学习干预的缘故。记忆控制小组分离观察的行为从记忆问题可能被考虑, 但这负担研究员和动物一样由于另外的工作7。第二个问题是动物做出决定的时刻: 一旦动物到达决策区 (所有三臂的交界处), 他们通常会向左和向右看, 权衡每只手臂的成本和利益, 然后做出决定。然而, 经过几次试验, 他们在到达决策区之前进行这样的计算, 直接跑到奖励臂上。因此, 这两个缺点-一只手臂的预偏向, 并发现决策的时刻-都高度中断了对电生理和神经影像数据的解释。
在本文所解释的方法中, 首选臂 (HRA) 由听觉线索提示, 并可能因试用而异。动物通过进入测试区 (图 1) 启动试验, 并通过 "鼻子戳" 的红外线门触发听觉提示, 该闸门已放置在三臂的交界处。音频信号 (20 分贝, 介于500和 1000 ms) 是从扬声器在目标臂的末尾播放。

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operant protocols for assessing the cost-benefit analysis during reinforced decision making by rodents

强化导向决策是根据利益的相对价值及其后果选择竞争的行动路线之间的能力。这一过程是人类正常行为的组成部分, 被证明被神经和精神紊乱, 如成瘾、精神分裂症和抑郁症所扰乱。啮齿类动物早已被用来揭示人类认知的神经生物学。为此, 制定了若干行为任务;然而, 大多数是非自动化的, 是劳动密集型的。最近开发的开源微控制器使研究人员能够自动化基于操作的任务来评估各种认知任务, 规范刺激演示, 改进数据记录, 从而提高研究成果。在这里, 我们描述了一种自动化的基于延迟的增强导向决策任务, 使用由定制软件程序控制的操作性 T 迷宫。利用这些决策任务, 我们展示了大鼠前扣带皮层局部场电位活动的变化, 同时进行了基于延迟的成本和效益决策任务。

这里提供的数据是从左眶皮质 (LFP) 和前扣带皮质 (ACC) 的记录使用双极电极 (粉煤灰涂层不锈钢)。表 1显示了每个训练阶段的行为习得长度。目标位置的坐标是从鼠脑图谱9确定的, 如下: 为 AAC, 1.2 毫米前的 bregma, 0.8 毫米侧向中线, 和2毫米腹侧的头骨;对于 bregma, 3.5 毫米的前部, 2.3 毫米侧向中线, 5.4 毫米腹侧的头骨。
录音被带通滤波 (0.01-250 Hz) 提取 LFPs, 然后取样在1000赫兹。利用多锥度10对 LFPs 进行了谱分析。采用五斯莱皮恩锥度和三的时间带宽乘积实现最佳谱浓度。用300毫秒的滑动窗口估计了时频图谱, 这是在 5 ms 台阶上转移到数据上的。为了更好地观察光谱功率与任务相关的调制, 并衰减 1/f 幂度问题, 所有图谱都是基线规范化的, 并使用 dBtf = 10log10 (Stf/mSf) 转换为分贝,当 Stf是频谱在时间t和频率f和 mSf是平均光谱所有时间点在基线之内在频带11。光谱功率计算的基线 (300 毫秒前鼻子戳), 刺激 (100 毫秒), 前室 (300 毫秒前进入房间), 和室 (600 毫秒) 时间窗口。统计分析采用非参数置换的t检验方法进行。
如图 2A的顶端行所示, 在 ACC 开始到刺激结束时, 在低 (4-12 hz) 和高 (45-85 hz) 频率功率中都有下降。通过对比腔室外的时间与腔内时间的比较, 频谱分析显示, 在 ACC 中, 振荡活动没有变化 (如图 2B的顶端行所示)。
当动物接近 IR 门时, 在光谱功率上的低频振荡也呈下降趋势;然而, 与 ACC (50-420ms) 的低频振荡相比, 这一现象较早前出现 (-80 毫秒), 持续时间更长。中/高频波段活动 (23-100 Hz) 在与刺激开始后增加 (图 2A, 底部行)。在前室和室时间窗口中, 当它们被比较时, 没有显著的变化 (图 2B, 底部行)。这些结果与以前的研究结果一致, 假设在2、12、13中, 双方都参与了基于价值的决策。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57907/57907fig1.jpg"> 图 1: 基于延迟的决策任务中选择试验的示意图.迷宫测量 60 cm x 10 cm x 40 cm。"开始" 框通过可伸缩的门连接到起始臂。另外两个可伸缩的门 (门 A 和门 B) 放置在每个球门臂上, 他们一起做一个房间来延缓动物获得奖赏的机会。门 A 被放置 12.5 cm 从入口点对每只胳膊和门 B 在食物之前被安置, 5 cm 从胳膊的末端。一个凸起的金属食品, 直径3厘米, 放置在每个目标臂的最远端, 2 厘米以上的迷宫地板。
该动物被放置在开始盒, 并允许接近和鼻子戳红外门 (IRB-1) 触发听觉刺激, 提示 HRA (在这个面板, 右臂)。IRB-2L 和 IRB-2R 时间戳动物的选择。如果动物向右转, 门 A 打开, 让动物进入手臂 (室), 并在动物进入后立即关闭。十五年代以后, 门 B 被打开给动物获得报偿。如果动物选择向左拐, (门 A 在左侧打开), 门 B 在进入左室后立即打开。IRB-3L 和 IRB-3R 时间戳动物进入房间的入口。
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/57907/57907fig2.jpg"> 图 2: ACC 和的神经活动的时间和光谱动力学.(A) 本小组在一次成功的高回报歧视期间, 显示 ACC (最高行) 和 "中行" 神经活动的时间频率图。通过从基线时间窗口中减去戳后时间窗口, 谱幂是基线规范化的。横坐标中的值0表示听觉刺激的开始。(B) 本小组在动物进入分庭时, 显示 ACC (顶行) 和地 (底行) 神经活动的时频图。会议厅时间窗口由预室时间窗口规范化。横坐标中的值0表示打开门的时间。彩色袋描绘了分贝尺度上光谱变化的程度。黑色矩形显示了显著偏差从机会水平 (p < 0.05 由双侧置换试验)。<a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/57907/57907fig2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<table border="0" cellpadding="0" cellspacing="0" width="699"><colgroup>
<col span="2">
<col>
<col>
<col>
<col>
<col>
</colgroup>
<tbody>
<tr height="77">
<td height="77" style="height:77px;width:88px;"></td>
			<td style="width:88px;">习惯</td>
			<td style="width:107px;">歧视培训</td>
			<td style="width:112px;">延迟培训 (5s)</td>
			<td style="width:109px;">延迟培训 (10s)</td>
			<td style="width:107px;">延迟培训 (15)</td>
			<td style="width:88px;">总</td>
		</tr>
<tr height="21">
<td height="21" style="height:21px;width:88px;">鼠1</td>
			<td style="width:88px;">3天</td>
			<td style="width:107px;">15天</td>
			<td style="width:112px;">8天</td>
			<td style="width:109px;">6天</td>
			<td style="width:107px;">5天</td>
			<td style="width:88px;">37天</td>
		</tr>
<tr height="21">
<td height="21" style="height:21px;width:88px;">鼠2</td>
			<td style="width:88px;">3天</td>
			<td style="width:107px;">18天</td>
			<td style="width:112px;">9天</td>
			<td style="width:109px;">6天</td>
			<td style="width:107px;">5天</td>
			<td style="width:88px;">41天</td>
		</tr>
<tr height="21">
<td height="21" style="height:21px;width:88px;">鼠3</td>
			<td style="width:88px;">3天</td>
			<td style="width:107px;">13天</td>
			<td style="width:112px;">7天</td>
			<td style="width:109px;">5天</td>
			<td style="width:107px;">6天</td>
			<td style="width:88px;">34天</td>
		</tr>
<tr height="21">
<td height="21" style="height:21px;width:88px;">鼠4</td>
			<td style="width:88px;">3天</td>
			<td style="width:107px;">15天</td>
			<td style="width:112px;">9天</td>
			<td style="width:109px;">6天</td>
			<td style="width:107px;">6天</td>
			<td style="width:88px;">39天</td>
		</tr>
<tr height="21">
<td height="21" style="height:21px;width:88px;">鼠5</td>
			<td style="width:88px;">3天</td>
			<td style="width:107px;">17天</td>
			<td style="width:112px;">8天</td>
			<td style="width:109px;">7天</td>
			<td style="width:107px;">5天</td>
			<td style="width:88px;">40天</td>
		</tr>
<tr height="21">
<td height="21" style="height:21px;width:88px;">鼠6</td>
			<td style="width:88px;">3天</td>
			<td style="width:107px;">16天</td>
			<td style="width:112px;">7天</td>
			<td style="width:109px;">6天</td>
			<td style="width:107px;">6天</td>
			<td style="width:88px;">38天</td>
		</tr>
</tbody></table>表 1: 6 只大鼠行为变异性和学习时间过程。

Watch this Scientific Journal Video about Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents at JoVE.com

Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents

啮齿动物强化决策中成本效益分析的操作协议

成本效益分析是大脑在决策过程中进行的一种称重尺度方法。在这里, 我们提出了一个训练老鼠的协议, 在一个以操作为基础的决策范式中, 老鼠选择更高的奖赏, 代价是等待十五年代的接收。

Reinforcement-guided decision making is the ability to choose between competing courses of action based on the relative value of the benefits and their ...

operant-protocols-for-assessing-cost-benefit-analysis-during

Universidad San Sebastian

Research

JoVE Journal

Neuroscience

5.9K 次观看.  The University of Melbourne. 成本效益分析是大脑在决策过程中进行的一种称重尺度方法。在这里, 我们提出了一个训练老鼠的协议, 在一个以操作为基础的决策范式中, 老鼠选择更高的奖赏, 代价是等待十五年代的接收。

视频: Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout&#160;or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e.&#160;8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e.&#160;one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.

The current study evaluates a novel procedure for assessing the reinforcing effects of palatable solutions in laboratory rats: intraoral self-administration. To this end, operant responding (i.e.&#160;lever pressing) for intraoral infusions of sweet solutions at different concentrations was measured on continuous and progressive ratios schedules of reinforcement.

一种新的方法为评估味质的实验室大鼠的补强性能：操作性口腔自我管理

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste ...

科研

行为学

A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. Higher cognitive functions that require precise control over sensorimotor responses such as decision-making and attentional modulation, however, are typically assessed in nonhuman primates. Despite the richness of primate behavior that allows multiple variants of these functions to be studied, the rodent model remains an attractive, cost-effective alternative to primate models. Furthermore, the ability to fully automate operant conditioning in rodents adds unique advantages over the labor intensive training of nonhuman primates while studying a broad range of these complex functions.
Here, we introduce a protocol for operantly conditioning rats on performing working memory tasks. During critical epochs of the task, the protocol ensures that the animal's overt movement is minimized by requiring the animal to 'fixate' until a Go cue is delivered, akin to nonhuman primate experimental design. A simple two alternative forced choice task is implemented to demonstrate the performance. We discuss the application of this paradigm to other tasks.

A fully automated protocol for rodent operant conditioning is proposed. The protocol relies on precise temporal control of behavioral events to investigate the extent to which this control influences neural activity underlying sensorimotor integration and cognitive control experiments.

为感觉运动整合与认知控制实验完全自动化的啮齿动物调理协议

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. ...

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one&#8217;s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer&#8217;s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

The ability to assess executive functions such as behavioral flexibility in rats is useful for investigating the neurobiology of cognition in both intact animals and disease models. Here we describe automated tasks for assessing strategy shifting and reversal learning, which are particularly sensitive to disruptions in prefrontal cortical networks.

操作性程序，以评估大鼠的行为灵活性

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these ...

Quantifying Social Motivation in Mice Using Operant Conditioning

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered shuttle boxes were equipped with two operant levers (left and right) and a food receptacle in one chamber, which was then divided from the second chamber by an automated guillotine door covered by a wire grid. Different stimulus mice, rotated across testing days, served as a social stimulus behind the wire grid, and were only visible following the opening of the guillotine door. Test mice were trained to lever press in order to open the door and gain access to the stimulus partner for 15 sec. The number of lever presses required to obtain the social reward progressively increased on a fixed schedule of 3. Testing sessions ended after test mice stopped lever pressing for 5 consecutive minutes. The last reinforced ratio or breakpoint can be used as a quantitative measure of social motivation. For the second paradigm, test mice were trained to discriminate between left and right lever presses in order to obtain either a food reward or the social reward. Mice were rewarded for every 3 presses of each respective lever. The number of food and social rewards can be compared as a measurement of the value placed upon each reward. The ratio of each reward type can also be compared between mouse strains and the change in this ratio can be monitored within testing sessions to measure satiation with a given reward type. Both of these operant conditioning paradigms are highly useful for the quantification of social motivation in mouse models of autism and other disorders of social behavior.

This article describes a new protocol for the quantitative measurement of social motivation in mice using operant conditioning for a social reward. The protocol is useful for the measurement of social motivation in mouse models of autism and other disorders of social behavior.

量化的社会动机小鼠使用操作条件反射

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered ...

A Fully Automated and Highly Versatile System for Testing Multi-cognitive Functions and Recording Neuronal Activities in Rodents

We have developed a fully automated system for operant behavior testing and neuronal activity recording by which multiple cognitive brain functions can be investigated in a single task sequence. The unique feature of this system is a custom-made, acoustically transparent chamber that eliminates many of the issues associated with auditory cue control in most commercially available chambers. The ease with which operant devices can be added or replaced makes this system quite versatile, allowing for the implementation of a variety of auditory, visual, and olfactory behavioral tasks. Automation of the system allows fine temporal (10 ms) control and precise time-stamping of each event in a predesigned behavioral sequence. When combined with a multi-channel electrophysiology recording system, multiple cognitive brain functions, such as motivation, attention, decision-making, patience, and rewards, can be examined sequentially or independently.

In this report, we present a fully automated and highly versatile system capable of simultaneously testing multi-cognitive behaviors and recording neuronal activities for rodents.

一个多认知功能测试，并记录在啮齿动物的神经元活动的完全自动化和高度灵活的系统

We have developed a fully automated system for operant behavior testing and neuronal activity recording by which multiple cognitive brain functions can be ...

神经科学

Testing for Metacognitive Responding Using an Odor-based Delayed Match-to-Sample Test in Rats

Metamemory involves the cognitive ability to assess the strength of one&#39;s memories. To explore the possibility of metamemory in non-human animals, numerous behavioral tasks have been created, many of which utilize an option to decline memory tests. To assess metamemory in rats, we utilized this decline-test option paradigm by adapting previous visual delayed-match-to-sample tests (DMTS)1,2 developed for primate species to an odor-based test suitable for rodents. First,&#160;rats are given a sample to remember by digging in a cup of scented sand. After a delay, the rat is presented with four distinctly scented cups, one of which contains the identical scent experienced during the sample; if this matching cup is selected, then the rat obtains a preferred, larger reward. Selection of any of the other three non-matching sand-filled scented cups results in no reward. Retention intervals are individually titrated such that subjects perform between 40 and 70% correct, therefore ensuring rats sometimes remember and sometimes forget the sample. Here, the operational definition of metamemory is the ability to distinguish between the presence and absence of memory through behavioral responding. Towards this end, on two-thirds of trials, a decline option is presented in addition to the four choice cups (choice trials). If the decline-test option- an unscented colored sand cup, is selected, the subject receives a smaller less-preferred reward and avoids the memory test. On the remaining third of trials, the decline-test option is not available (forced trials), causing subjects to guess the correct cup when the sample is forgotten. On choice tests, subjects that know when they remember should select the decline option when memory is weak rather than take the test and choose incorrectly. Therefore, significantly higher performance on chosen tests as compared to forced memory tests is indicative of the adaptive use of the decline-test response and metacognitive responding.

This protocol describes a method for investigating the possibility of metamemory, or memory awareness, in rodents. The odor-based delayed-matching-to-sample paradigm is a novel, ecologically-relevant behavioral test useful for determining the extent to which rodents can adaptively respond based on cognitively monitoring the strength of their memory states.

用基于气味的延迟配对试验对大鼠元认知应答的测试

Metamemory involves the cognitive ability to assess the strength of one&#39;s memories. To explore the possibility of metamemory in non-human animals, ...

An Automated T-maze Based Apparatus and Protocol for Analyzing Delay- and Effort-based Decision Making in  Free Moving Rodents

Many neurological and psychiatric patients demonstrate difficulties and/or deficits in decision making. Rodent models are helpful to produce a deeper understanding of the neurobiological causes underlying the decision-making problems. A cost-benefit based T-maze task is used for measuring decision making in which rodents choose between a high reward arm (HRA) and a low reward arm (LRA). There are two paradigms of the T-maze decision-making task, one in which the cost is a time delay and the other in which it is physical effort. Both paradigms require a tedious and labor-intensive management of experimental animals, multiple doors, pellet reward, and arm choice recordings. In the current work, we invented an apparatus based on traditional T-maze with full automation for pellet delivery, door management and choice recordings. This automated setup can be used for the evaluation of both delay- and effort-based decision making in rodents. With the protocol described here, our lab investigated the decision-making phenotypes of multiple genetically modified mice. In the representative data, we showed that the mice with ablated medial habenular showed aversions of both delay and effort and tended to choose the immediate and effortless reward. This protocol helps to decrease the variability caused by experimenter intervention and to enhance experiment efficiency. In addition, chronic silicon probe or microelectrode recording, fiber-optic imaging and/or manipulation of neural activity can be easily applied during the decision-making task using the setup described here.

This article introduces an automated T-maze apparatus that we invented, and a protocol based on this apparatus for analyzing delay-based decision making and effort-based decision making in free moving rodents.

基于自动 T 迷宫的自由移动啮齿动物延迟和努力决策分析装置及协议

Many neurological and psychiatric patients demonstrate difficulties and/or deficits in decision making. Rodent models are helpful to produce a deeper ...

Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is a meaningful concept because it is associated with psychiatric conditions in humans and with maladaptive behavior in non-human animals. It is believed that impulsivity is composed of separate factors. There are laboratory protocols devised to assess each of these factors using standardized automated equipment. Delay discounting is associated with the incapacity to be motivated by delayed outcomes. This factor is evaluated through intertemporal choice protocols, which consist&#160;of presenting the individual with a choice situation involving an immediate reward and a larger but delayed reward. Response inhibition deficit is associated with the incapacity to withhold prepotent responses. Differential reinforcement of low rates (DLR) and feature-negative discrimination protocols assess the response inhibition deficit factor of impulsivity. The former imposes a condition to a motivated individual in which most wait a minimum period of time for a response to be rewarded. The latter evaluates the capacity of individuals to refrain from food seeking responses when a signal of the absence of food is presented. The purpose of these protocols is to construct an objective quantitative measure of impulsivity, which serves to make cross-species comparisons, allowing the possibility of translational research. The advantages of these particular protocols include their easy set-up and application, which stems from the relatively small amount of equipment needed and the automated nature of these protocols.

We present three protocols that assess different forms of impulsivity in rats and other small mammals. Intertemporal choice procedures evaluate the tendency to discount the value of delayed outcomes. Differential reinforcement of low rates and feature-negative discrimination evaluate response inhibition capacity with and without punishment for inappropriate responses, respectively.

评估大鼠冲动不同表现的三个实验室程序

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is ...

A Conflict Model of Reward-seeking Behavior in Male Rats

The present protocol describes a novel conflict task as a model of inhibitory control in rats. In this model, a natural rewarding stimulus (sexual stimulus) that represents a high-value reward, and the aversive stimuli (pins), are concurrently presented. The male rats have to climb or jump over the obstacle full of pins to approach and investigate the sexual partner. If the animal persists in their approaching behavior regardless of the aversive stimuli, it is considered as a maladaptive or risky reward-seeking behavior. The conflict task permits the evaluation of deficit in inhibitory control resulting from exposure to abused drug, such as morphine, or a stressful event. 
The main advantage of this model is that it provides a simple and quick way to discover the deficit in inhibitory control after exposure to opiate drugs or other stressful events. In addition to opiates, this behavioral model would also be useful for quickly discovering the inhibitory control deficits induced by other addictive drugs. However, the limitation is that the male rats' performance may be subject to exercising effects with repeated testing under this conflict task. In the future, one can hope that the individuals with the compulsive phenotype of reward-seeking behavior after exposure to opiates will be identified based on modifying this conflict model.

This conflict model is used to measure the impairment of inhibitory control after exposure to addictive drugs, or other factors that may influence inhibitory control. A sexual stimulus and an aversive obstacle are concurrently presented, thus male rats have to conquer the obstacle to approach the sexual reward.

雄性大鼠寻救行为的冲突模型

The present protocol describes a novel conflict task as a model of inhibitory control in rats. In this model, a natural rewarding stimulus (sexual ...

Assessment of Stress Effects on Cognitive Flexibility using an Operant Strategy Shifting Paradigm

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and duration of the stressor; 2) type of cognitive function under study; and 3) timing of the stressor in relation to learning or executing the cognitive task. Furthermore, sex differences among the effects of stress on cognitive function have been widely documented. Described here is an adaptation of an automated operant strategy shifting paradigm to assess how variations in stress affect cognitive flexibility in male and female Sprague Dawley rats. Specifically, restraint stress is used before or after training in this operant-based task to examine how stress affects cognitive performance in both sexes. Particular brain areas associated with each task in this automated paradigm have been well-established (i.e., the medial prefrontal cortex and orbitofrontal cortex). This allows for targeted manipulations during the experiment or the assessment of particular genes and proteins in these regions upon completion of the paradigm. This paradigm also allows for the detection of different types of performance errors that occur after stress, each of which has defined neural substrates. Also identified are distinct sex differences in perseverative errors after a repeated restraint stress paradigm. The use of these techniques in a preclinical model may reveal how stress affects the brain and impairs cognition in psychiatric disorders, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), which display marked sex differences in prevalence.

Stressful life events impair cognitive function, increasing the risk of psychiatric disorders. This protocol illustrates how stress affects cognitive flexibility using an automated operant strategy shifting paradigm in male and female Sprague Dawley rats. Specific brain areas underlying particular behaviors are discussed, and translational relevance of results are explored.

使用操作策略转移范式评估压力对认知灵活性的影响

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and ...