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啮齿动物的线索性和情境性恐惧条件反射

Cued and Contextual Fear Conditioning for Rodents

作者信息

Curzon Peter, Rustay Nathan R., Browman Kaitlin E.

PMID:21204331
Abstract

Understanding what an animal learns when exposed to novelty is of great interest to behavioral neuroscientists, but it can be challenging to understand what information is acquired in a particular learning session. The behavior of an animal has to be quantified using either visual or mechanical measures of a particular response. One way of elucidating mechanisms involved in discrete learning sessions is to study associative learning processes. Simplistically, associative learning is an adaptive process that allows an organism to learn to anticipate events. One form of associative learning that has been used in multiple species, including humans, is eye-blink conditioning. The most common species used, the rabbit, has yielded interesting results, especially in identifying and elucidating the involvement of the cerebral cortex. Similar procedures have been used in cats, rats, and humans. Another form of associative learning that has gained popularity with behavioral pharmacologists is fear conditioning. While the eye-blink procedure has overlap with context/cue fear conditioning and in many cases yields similar results, there are some basic differences between fear conditioning and eye-blink conditioning. One main difference is that eye-blink conditioning takes many more training trials to establish. Fear conditioning has gained popularity, in large part as a result of the need to characterize mutant mice and the effects of genetic alterations; therefore, this chapter primarily focuses on fear conditioning. Fear conditioning to either a cue or a context represents a form of associative learning that has been well used in many species [1]. The majority of the experiments reported in the literature involve the mouse; however, there is also a generous proportion of the literature devoted to the rat. There are also several reports in higher species that are not covered in this chapter. In general any of the procedures described in this chapter can be used for either the rat or the mouse. The dependent measure used in contextual and cued (delay or trace) fear conditioning is a freezing response that takes place following pairing of an unconditioned stimulus (US), such as foot shock or air puff, with a conditioned stimulus (CS), a particular context and/or such a cue. In the case of rats and mice, this US is generally a foot shock. Obviously, if in a conditioning context one administers a foot shock that is paired with a tone, there will be learning not only to the tone, but also to the context. Two types of conditioning that are typically employed are delay or trace conditioning. Delay conditioning refers to a situation in which the US is administered to co-terminate with or occur immediately after the CS. Trace conditioning differs from delay conditioning in that the US follows an empty (“trace”) interval that separates the cessation of the CS from the onset of the US. Trace conditioning adds additional complexity to delay conditioning, as the time interval between the CS and US requires the formation of a temporal relationship between the two stimuli. In this chapter we discuss the various challenges inherent in this type of procedure in order to enable the experimenter to set the conditions to best answer the questions being posed. One of the biggest advantages of cued and contextual fear conditioning in the rodent is that they are forms of passive learning that can be used in many strains of mice and rats, even when more pronounced motor deficits are problematic in other learning assays. As a consequence of these procedural advantages, contextual fear conditioning is gaining popularity, especially in the phenotyping of transgenic mice.

摘要

了解动物在接触新事物时学到了什么,这对行为神经科学家来说极具吸引力,但要弄清楚在特定学习过程中获取了哪些信息可能具有挑战性。必须使用对特定反应的视觉或机械测量方法来量化动物的行为。阐明离散学习过程中涉及的机制的一种方法是研究联想学习过程。简单来说,联想学习是一个适应性过程,使生物体能够学会预测事件。在包括人类在内的多个物种中都使用过的一种联想学习形式是眨眼条件反射。最常使用的物种是兔子,它产生了有趣的结果,特别是在识别和阐明大脑皮层的参与方面。类似的程序也已在猫、大鼠和人类中使用。行为药理学家中越来越受欢迎的另一种联想学习形式是恐惧条件反射。虽然眨眼程序与情境/线索恐惧条件反射有重叠,并且在许多情况下产生相似的结果,但恐惧条件反射和眨眼条件反射之间存在一些基本差异。一个主要区别是眨眼条件反射需要更多的训练试验才能建立。恐惧条件反射之所以受到欢迎,很大程度上是因为需要对突变小鼠和基因改变的影响进行表征;因此,本章主要关注恐惧条件反射。对线索或情境的恐惧条件反射代表了一种联想学习形式,已在许多物种中得到很好的应用[1]。文献中报道的大多数实验涉及小鼠;然而,也有相当一部分文献致力于大鼠。本章未涵盖高等物种中的一些报道。一般来说,本章中描述的任何程序都可用于大鼠或小鼠。情境和线索(延迟或痕迹)恐惧条件反射中使用的因变量测量是一种冻结反应,它发生在将无条件刺激(如足部电击或吹气)与条件刺激(特定情境和/或此类线索)配对之后。就大鼠和小鼠而言,这种无条件刺激通常是足部电击。显然,如果在条件反射情境中给予与音调配对的足部电击,不仅会对音调产生学习,还会对情境产生学习。通常采用的两种条件反射类型是延迟或痕迹条件反射。延迟条件反射是指无条件刺激与条件刺激同时结束或在条件刺激之后立即给予的情况。痕迹条件反射与延迟条件反射的不同之处在于,无条件刺激跟随一个空的(“痕迹”)间隔,该间隔将条件刺激的停止与无条件刺激的开始分开。痕迹条件反射给延迟条件反射增加了额外的复杂性,因为条件刺激和无条件刺激之间的时间间隔需要在这两种刺激之间形成时间关系。在本章中,我们讨论了这种类型程序固有的各种挑战,以使实验者能够设置条件,以最好地回答所提出的问题。啮齿动物中线索和情境恐惧条件反射的最大优点之一是它们是被动学习的形式,可用于许多品系的小鼠和大鼠,即使在其他学习试验中更明显的运动缺陷有问题时也是如此。由于这些程序上的优点,情境恐惧条件反射越来越受欢迎,特别是在转基因小鼠的表型分析中。

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