Cued fear memory generalization increases over time.

Fear memory is a highly stable and durable form of memory, even over vast (remote) time frames. Nevertheless, some elements of fear memory can be forgotten, resulting in generalization. The purpose of this study is to determine how cued fear memory generalizes over time and measure underlying patterns of cortico-amygdala synaptic plasticity. We established generalization gradients at recent (1-d) and remote (30-d) retention intervals following auditory cued fear conditioning in adult male C57BL/6 mice. Results revealed a flattening of the generalization gradient (increased generalization) that was dissociated from contextual fear generalization, indicating a specific influence of time on cued fear memory performance. This effect reversed after a brief exposure to the novel stimulus soon after learning. Measurements from cortico-amygdala imaging of the activity-regulated cytoskeletal Arc/arg 3.1 (Arc) protein using immunohistochemistry after cued fear memory retrieval revealed a stable pattern of Arc expression in the dorsolateral amygdala, but temporally dynamic expression in the cortex. Over time, increased fear memory generalization was associated with a reduction in Arc expression in the agranular insular and infralimbic cortices while discrimination learning was associated with increased Arc expression in the prelimbic cortex. These data identify the dorsolateral amygdala, medial prefrontal, and insular cortices as loci for synaptic plasticity underlying cued fear memory generalization over time.

Current understanding of fear learning and memory in humans and animal models and the value of a linguistic approach for analyzing fear learning and memory in humans.

Fear is an emotion that serves as a driving factor in how organisms move through the world. In this review, we discuss the current understandings of the subjective experience of fear and the related biological processes involved in fear learning and memory. We first provide an overview of fear learning and memory in humans and animal models, encompassing the neurocircuitry and molecular mechanisms, the influence of genetic and environmental factors, and how fear learning paradigms have contributed to treatments for fear-related disorders, such as posttraumatic stress disorder. Current treatments as well as novel strategies, such as targeting the perisynaptic environment and use of virtual reality, are addressed. We review research on the subjective experience of fear and the role of autobiographical memory in fear-related disorders. We also discuss the gaps in our understanding of fear learning and memory, and the degree of consensus in the field. Lastly, the development of linguistic tools for assessments and treatment of fear learning and memory disorders is discussed.