Multiphoton microscopy is one of several new technologies providing unprecedented insight into the activity dynamics and function of neural circuits. Unfortunately, many of these technologies require experimentation in head-restrained animals, greatly limiting the behavioral repertoire that can be studied with each approach. This issue is especially evident in drug addiction research, as no laboratories have coupled multiphoton microscopy with simultaneous intravenous drug self-administration, the gold standard of behavioral paradigms for investigating the neural mechanisms of drug addiction. Such experiments would be transformative for addiction research as one could measure or perturb an array of behavior and drug-related adaptations in precisely defined neural circuit elements over time, including but not limited to dendritic spine plasticity, neurotransmitter release, and neuronal activity. Here, we describe a new experimental assay wherein mice self-administer drugs of abuse while head-restrained, allowing for simultaneous multiphoton imaging. We demonstrate that this approach enables longitudinal tracking of activity in single neurons from the onset of drug use to relapse. The assay can be easily replicated by interested labs for relatively little cost with readily available materials and can provide unprecedented insight into the neural underpinnings of substance use disorder.

中文翻译：

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头部受约束的小鼠中的药物自我给药，可同时进行多光子成像

多光子显微镜技术是对神经回路的活动动力学和功能提供空前洞察力的几种新技术之一。不幸的是，许多这些技术都需要在头部受限的动物中进行实验，这极大地限制了每种方法都可以研究的行为方式。这个问题在药物成瘾研究中尤为明显，因为没有实验室将多光子显微镜与同时进行静脉药物自我管理相结合，这是研究药物成瘾神经机制的行为范式的黄金标准。这样的实验对于成瘾研究将是变革性的，因为随着时间的推移，人们可以测量或扰动精确定义的神经回路元件中的一系列行为和与药物相关的适应性变化，包括但不限于树突棘的可塑性，神经递质释放和神经元活动。在这里，我们描述了一种新的实验测定法，其中小鼠在克制头部的同时自我管理滥用药物，从而允许同时进行多光子成像。我们证明了这种方法可以使从吸毒到复发的单个神经元的活动纵向跟踪。感兴趣的实验室可以使用容易获得的材料以相对较低的成本轻松地重复进行该测定，并且可以对物质使用障碍的神经基础提供空前的见识。我们证明了这种方法可以使从吸毒到复发的单个神经元的活动纵向跟踪。感兴趣的实验室可以使用容易获得的材料以相对较低的成本轻松地重复进行该测定，并且可以对物质使用障碍的神经基础提供空前的见识。我们证明了这种方法可以使从吸毒到复发的单个神经元的活动纵向跟踪。感兴趣的实验室可以使用容易获得的材料以相对较低的成本轻松地重复进行该测定，并且可以对物质使用障碍的神经基础提供空前的见识。