Exploring the neurobehavioural impacts of combined early life and adult stress on decision making under uncertainty

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.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Stupart, Olivia

Advisor dc:contributor.advisor

• Dalley, Jeffrey

• Maternal Separation
• Early life stress
• Decision-making
• Monoamines
• Behavioural flexibility
• Cortisol
• Mitochondria
• Magnetic Resonance Imaging

Licence

• https://www.repository.cam.ac.uk/bitstreams/8fd228a3-9417-4522-a9fc-dc0e12777fa8/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

Author Identifier

0000-0001-9973-8889

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/376505