Assaying Fear Memory Discrimination and Generalization: Methods and Concepts

Abstract

Generalization describes the transfer of conditioned responding to stimuli that perceptually differ from the original conditioned stimulus. One arena in which discriminant and generalized responding is of particular relevance is when stimuli signal the potential for harm. Aversive (fear) conditioning is a leading behavioral model for studying associative learning and memory processes related to threatening stimuli. This article describes a step‐by‐step protocol for studying discrimination and generalization using cued fear conditioning in rodents. Alternate conditioning paradigms, including context generalization, differential generalization, discrimination training, and safety learning, are also described. The protocol contains instructions for constructing a cued fear memory generalization gradient and methods for isolating discrete cued‐from‐context cued conditioned responses (i.e., “the baseline issue”). The preclinical study of generalization is highly pertinent in the context of fear learning and memory because a lack of fear discrimination (overgeneralization) likely contributes to the etiology of anxiety‐related disorders and post‐traumatic stress disorder. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Tone cued fear generalization gradient Basic Protocol 2: Quantification of freezing Support Protocol: Alternate conditioning paradigms

Role of the anterior insular cortex in restraint-stress induced fear behaviors

“…With further development and validation, our animal model may be useful for studying how fear and anxiety generalization occurs. Generalization is a fear response triggered by stimuli that are partially similar to the original stimulation 26 . It is a main symptom of anxiety disorders.…”

Formation of False Context Fear Memory Is Regulated by Hypothalamic Corticotropin-Releasing Factor in Mice

“…Fear generalization to innocuous stimuli acting as reminders of the trauma, even in a safe place or environment, is one of the central problema and a hallmark of PTSD [ 29 ]. It has been further posited that the generalization will be enhanced if the new context is similar, but not completely different, from the training context, due to memory source confusion [ 30 ]. False memories can be spontaneously produced after an extreme fear experience but, classically, the term “false memory” applies to memory formed without actual experience of the event.…”

“…False memories can be spontaneously produced after an extreme fear experience but, classically, the term “false memory” applies to memory formed without actual experience of the event. If “fear generalization” is defined as the actual memory of a fear experience that transfer a conditioned response to stimuli that perceptually differ from the original conditioned stimulus [ 30 ], fear generalization may also be the same as false fear memory. In rodents, fear generalization has been shown to be induced when mice were exposed to contexts soon after training [ 26 ].…”

Young Astrocytic Mitochondria Attenuate the Elevated Level of CCL11 in the Aged Mice, Contributing to Cognitive Function Improvement

“…The Barnes maze test [ 83 , 84 ] and fear conditioning test [ 85 , 86 ] with modifications were used to assess spatial and associative learning and memory in mice, respectively. Briefly, the Barnes maze test was performed using an elevated circular platform that had 20 holes evenly spaced.…”