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用于操纵啮齿动物注意力、冲动性和行为灵活性的光遗传学和化学遗传学方法。

Optogenetic and chemogenetic approaches to manipulate attention, impulsivity and behavioural flexibility in rodents.

作者信息

Carr Madison R, de Vries Taco J, Pattij Tommy

机构信息

Department of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center.

Department of Molecular and Cellular Neuroscience, CNCR, VU University, Amsterdam, The Netherlands.

出版信息

Behav Pharmacol. 2018 Oct;29(7):560-568. doi: 10.1097/FBP.0000000000000425.

Abstract

Studies manipulating neural activity acutely with optogenetic or chemogenetic intervention in behaving rodents have increased considerably in recent years. More often, these circuit-level neural manipulations are tested within an existing framework of behavioural testing that strives to model complex executive functions or symptomologies relevant to multidimensional psychiatric disorders in humans, such as attentional control deficits, impulsivity or behavioural (in)flexibility. This methods perspective argues in favour of carefully implementing these acute circuit-based approaches to better understand and model cognitive symptomologies or their similar isomorphic animal behaviours, which often arise and persist in overlapping brain circuitries. First, we offer some practical considerations for combining long-term, behavioural paradigms with optogenetic or chemogenetic interventions. Next, we examine how cell-type or projection-specific manipulations to the ascending neuromodulatory systems, local brain region or descending cortical glutamatergic projections influence aspects of cognitive control. For this, we primarily focus on the influence exerted on attentional and motor impulsivity performance in the (3-choice or) 5-choice serial reaction time task, and impulsive, risky or inflexible choice biases during alternative preference, reward discounting or reversal learning tasks.

摘要

近年来,在行为啮齿动物中通过光遗传学或化学遗传学干预对神经活动进行急性操纵的研究大幅增加。更常见的是,这些电路水平的神经操纵是在现有的行为测试框架内进行的,该框架致力于模拟与人类多维精神疾病相关的复杂执行功能或症状,如注意力控制缺陷、冲动性或行为(不)灵活性。这种方法观点主张谨慎实施这些基于急性电路的方法,以更好地理解和模拟认知症状或其类似的同构动物行为,这些行为通常出现在重叠的脑电路中并持续存在。首先,我们提供一些将长期行为范式与光遗传学或化学遗传学干预相结合的实际考虑因素。接下来,我们研究对上行神经调节系统、局部脑区或下行皮质谷氨酸能投射进行细胞类型或投射特异性操纵如何影响认知控制的各个方面。为此,我们主要关注在(三选一或)五选串行反应时任务中对注意力和运动冲动性表现的影响,以及在替代偏好、奖励折扣或逆向学习任务中冲动、冒险或不灵活的选择偏差。

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