Behavioural and neuroimmune responses to early life stress on contextual fear and extinction memory.

Richardson, Peter 2024. Behavioural and neuroimmune responses to early life stress on contextual fear and extinction memory. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Early life stress (ELS) profoundly affects brain development and increases the risk of psychiatric disorders such as anxiety and PTSD, which are associated with abnormal fear learning, memory and extinction Despite this, the mechanisms—especially those involving neuro-immune and stress system interactions in fear memory formation and extinction—are not well understood. This thesis investigates how ELS affects contextual fear conditioning (CFC), contextual fear memory (CFM) and extinction in adulthood with an emphasis on exploring sex differences. Chapter 3 demonstrates that rats, having undergone a period of ELS exhibit heightened fear memories compared to their non-stressed counterparts. Notably, male animals exposed to ELS show evidence of a resistance to extinction of CFM. During extinction recall, ELS-exposed males exhibit potentially enhanced recall, indicated by lower freezing levels, suggesting a resilience to stress, while females, show very low levels of conditioned freezing under the same CFC training. Chapter 4 explores variations in fear expression through ultrasonic vocalisations and shows that measuring 22kHz reveals an effect of ELS on CFC in females and males as an alternative measure of fear memory. ELS enhances CFM in males, but levels were too low in females to conduct meaningful analysis past CFM recall. Furthermore, this work delves into neuro-immunological mechanisms in Chapters 5 and 6, investigating whether the neuroimmune system contributes to the changes in CFM and extinction observed after ELS. While cytokine levels in the CA1 of the hippocampus after CFM recall and extinction differed, there was no additional effect of ELS (Chapter 5). There were changes in the morphology of microglia in the IL region of the PFC after CFC that were both ELS and sex dependent (Chapter 6). This research advances our understanding of how ELS modifies CFC and extinction learning and underscores the potential involvement of neuro-immunological mechanisms. The identified differences suggest potential therapeutic targets for intervening in adulthood following a stratification system focusing on exposure to ELS and with the goal of ameliorating the fear memory and extinction deficits characterising certain neuropsychiatric disorders.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	7 January 2025
Last Modified:	07 Jan 2025 10:37
URI:	https://orca.cardiff.ac.uk/id/eprint/175053

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