Fear conditioning: Insights into learning, memory and extinction and its relevance to clinical disorders

Trent, Simon; Abdullah, Muhammad Hazim; Parwana, Krishma; Valdivieso, Maria Alcocer; Hassan, Zurina; Müller, Christian P.

Abstract

Fear, whether innate or learned, is an essential emotion required for survival. The learning, and subsequent memory, of fearful events enhances our ability to recognise and respond to threats, aiding adaptation to new, ever-changing environments. Considerable research has leveraged associative learning protocols such as contextual or auditory forms of fear conditioning in rodents, to understand fear learning, memory consolidation and extinction phases of memory. Such assays have led to detailed characterisation of the underlying neurocircuitry and neurobiology supporting fear learning processes. Given fear processing is conserved across rodents and humans, fear conditioning experiments provide translational insights into fundamental memory processes and fear-related pathologies. This review examines associative learning protocols used to measure fear learning, memory and extinction, before providing an overview on the underlying complex neurocircuitry including the amygdala, hippocampus and medial prefrontal cortex. This is followed by an in-depth commentary on the neurobiology, particularly synaptic plasticity mechanisms, which regulate fear learning, memory and extinction. Next, we consider how fear conditioning assays in rodents can inform our understanding of disrupted fear memory in human disorders such as post-traumatic stress disorder (PTSD), anxiety and psychiatric disorders including schizophrenia. Lastly, we critically evaluate fear conditioning protocols, highlighting some of the experimental and theoretical limitations and the considerations required when conducting such assays, alongside recent methodological advancements in the field. Overall, rodent-based fear conditioning assays remain central to making progress in uncovering fundamental memory phenomena and understanding the aetiological mechanisms that underpin fear associated disorders, alongside the development of effective therapeutic strategies.

Citation

Trent, S., Abdullah, M. H., Parwana, K., Valdivieso, M. A., Hassan, Z., & Müller, C. P. (2025). Fear conditioning: Insights into learning, memory and extinction and its relevance to clinical disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 138, Article 111310. https://doi.org/10.1016/j.pnpbp.2025.111310

• Journal Article Type: Article
• Acceptance Date: Mar 2, 2025
• Online Publication Date: Mar 6, 2025
• Publication Date: 2025-04
• Deposit Date: Mar 18, 2025
• Journal: Progress in Neuro-Psychopharmacology and Biological Psychiatry
• Print ISSN: 0278-5846
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 138
• Article Number: 111310
• DOI: https://doi.org/10.1016/j.pnpbp.2025.111310
• Keywords: Learning; Memory; Fear; Conditioning; Extinction; Context; PTSD
• Public URL: https://keele-repository.worktribe.com/output/1108435
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0278584625000648?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: Fear conditioning: Insights into learning, memory and extinction and its relevance to clinical disorders; Journal Title: Progress in Neuro-Psychopharmacology and Biological Psychiatry; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.pnpbp.2025.111310; Content Type: article; Copyright: © 2025 The Authors. Published by Elsevier Inc.