Behavioral verification of associative learning in whisker-related fear conditioning in mice

Abstract

Fear-conditioning is one of the most widely used paradigms in attempts to unravel the processes and mechanisms underlying learning and plasticity. In most Pavlovian conditioning paradigms an auditory stimulus is used as the conditioned stimulus (CS), but conditioning to a tactile CS can also be accomplished. The whisker-to-barrel tactile system in mice offers a convenient way to investigate the brain pathways and mechanisms of learning and plasticity of the cerebral cortex. To support the claim that an animal learns during conditioning sessions and that the resulting plastic changes are associative in nature, objective measures of behavior are necessary. Multiple types of conditioned responses can develop depending on the training situation, CS and unconditioned stimulus (UCS) characteristics. These include physiological responses such as salivation, heart rate, and galvanic skin reaction, and also behavioral responses such as startle reflex potentiation or suppression of an ongoing behavior. When studying learning with the whisker system in behaving mice, stimulation of individual whiskers in a well-controlled manner may require animal restraint, which has the disadvantage of limiting the observation of potential behavioral responses. Stimulation of whiskers in a neck-restraining apparatus evokes head movements. When whisker stimulation (CS) is paired with an aversive UCS during conditioning, the number of head movements decrease in the course of the training. This reaction, called minifreezing, resembles the frequently used behavioral measure known as the freezing response. However, this is only applicable for freely moving animals. This article will review experimental evidence confirming that minifreezing is a relevant index of association formation between the neutral CS and aversive UCS.

Functional organization of the human amygdala in appetitive learning

“…In particular, considerable attention has been devoted to understand the function of the amygdala in fear conditioning (e.g. Knapska et al 2012, for a review, see Cybulska-Klosowicz 2016). Yet, it is now indisputable that this structure is involved not only in aversive conditioning but also reward learning.…”

Where do we stand on fMRI in awake mice?

“…These are inter-related since (in theory) an animal that is well acclimated (less stressed) will struggle less (less motion). Though, it should be noted that freezing is an established fear response in mice ( Cybulska-Kłosowicz 2016 ), and an awake animal that is well acclimated will engage in a normal range of movements (e.g. grooming [ Desjardins et al.…”