Cued and Contextual Fear Conditioning for Rodents

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.