2026-09-24T09:05:23Zhttps://api.repository.cam.ac.uk/server/oai/request

oai:www.repository.cam.ac.uk:1810/3765052025-12-20T03:40:16Zcom_1810_245310com_1810_256062col_1810_245312

Exploring the neurobehavioural impacts of combined early life and adult stress on decision making under uncertainty https://doi.org/10.17863/CAM.113718 Stupart, Olivia 0000000199738889 Dalley, Jeffrey The primary goal of this thesis was to investigate the persistent neurobehavioural outcomes of early life stress (ELS) using the repeated maternal separation (MS) procedure in rats. The specific hypothesis tested was that stress effects accumulate over the developmental lifespan, resulting in either stress resilience or vulnerability in adulthood. Early postnatal life is a critical period for stress-induced plasticity; however, the precise interactive effects of cumulative stress from early life to adulthood remain poorly understood. This thesis underscores the importance of translational research in examining the neural and psychological mechanisms underlying behavioural endophenotypes linked to stress-related disorders such as depression and anxiety. A key focus was on how stress affects decision-making processes involving uncertainty and ambiguity. Two operant tasks were employed: a probabilistic reversal learning (PRL) task and an ambiguous cue task (ACT). Several novel findings emerged. Firstly, MS stress had a lasting effect on corticosterone signalling regulation, resulting in generally diminished circulatory levels during non-stressed baseline conditions. Secondly, MS led to a blunting of negative cognitive biases typically induced by affective stimuli in an ACT. Thirdly, “stress memories” from early MS may be partly mediated by alterations in mitochondrial signalling in the prefrontal cortex (PFC). Fourthly, early life separation stress did not produce volumetric changes in brain regions commonly associated with stress impacts, including the hippocampus (HPC), PFC, and amygdala (AMY). Overall, these findings suggest that early MS stress alone is insufficient to produce overt neurobehavioural outcomes in adulthood and may confer some resilience. However, early MS stress appears to influence the interaction with subsequent stressors, potentially leading to more severe impacts and contributing to the emergence of stress-related mood and emotional disorders. University of Cambridge 2024-07-19 Thesis Doctoral Doctor of Philosophy (PhD) eng Sims Scholarship, University of Cambridge University of Cambridge, Clinical School https://www.repository.cam.ac.uk/handle/1810/376505 https://www.repository.cam.ac.uk/bitstreams/4a9a7dac-5be4-42bf-8641-d07a3f94bb2a/download 0c0b3a7f92f18e7eae74b1af9a977600 https://www.repository.cam.ac.uk/bitstreams/8fd228a3-9417-4522-a9fc-dc0e12777fa8/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Maternal Separation Early life stress Decision-making Monoamines Behavioural flexibility Cortisol Mitochondria Magnetic Resonance Imaging