Biology subjects

Wilkinson, M. P.

Publications and source records attributed to Wilkinson, M. P..

2 recordsLinked to original sources

bioRxiv2024

Analysis of Hippocampal Synaptic Function in a Rodent Model of Early Life Stress

BackgroundEarly life stress (ELS) is an important risk factor in the aetiology of depression. Developmental glucocorticoid exposure impacts multiple brain regions with the hippocampus being particularly vulnerable. Hippocampal mediated behaviours are dependent upon the ability of neurones to undergo long-term potentiation (LTP), an N-methyl-D-aspartate receptor (NMDAR) mediated process. In this study we investigated the effect of ELS upon hippocampal NMDAR function. MethodsHooded Long-Evans rat pups (n=82) were either undisturbed or maternally separated for 180 minutes per day (MS180) between post-natal day (PND) 1 and PND14. Model validation consisted of sucrose preference (n=18) and novelty supressed feeding (NSFT, n=34) tests alongside assessment of corticosterone (CORT) and paraventricular nucleus (PVN) cFos reactivity to stress and hippocampal neurogenesis (all n=18). AMPA/NMDA ratios (n=19), miniEPSC currents (n=19) and LTP (n=15) were assessed in whole-cell patch clamp experiments in CA1 pyramidal neurones. ResultsMS180 animals showed increased feeding latency in the NSFT alongside increased overall CORT in the restraint stress experiment and increased PVN cFos expression in males but no changes in neurogenesis or sucrose preference. MS180 was associated with a lower AMPA/NMDA ratio with no change in miniEPSC amplitude or area. There was no difference in short- or long-term potentiation between MS180 and control animals nor were there any changes during the induction protocol. ConclusionsThe MS180 model showed a behavioural phenotype consistent with previous work. MS180 animals showed increased NMDAR function with preliminary evidence suggesting that this was not concurrent with an increase in LTP.

neuroscience↗

bioRxiv2020

Investigation of reward learning and feedback sensitivity in non-clinical participants with a history of early life stress

Early life stress (ELS) is an important risk factor for the development of depression. Impairments in reward learning and feedback sensitivity are suggested to be an intermediate phenotype in depression aetiology therefore we hypothesised that similar impairments are present in healthy adults with a history of ELS. We recruited 64 adults with high levels of ELS and no diagnosis of a current mental health disorder and 65 controls. Participants completed the probabilistic reversal learning task and probabilistic reward task followed by depression, anhedonia, social status, and stress scales. Participants with high levels of ELS showed decreased positive feedback sensitivity in the probabilistic reversal learning task compared to controls. High ELS participants also trended towards possessing a decreased model-free learning rate. This was coupled with a decreased learning ability in the acquisition phase of block 1 following the practice session. Neither group showed a reward induced response bias in the probabilistic reward task however high ELS participants exhibited decreased stimuli discrimination. Due to the PRT not meeting its primary endpoint a separate cohort of control participants were tested in a modified PRT where they showed a response bias. This indicates the PRT can be successfully carried out online. Overall, these data suggest that healthy participants without a mental health diagnosis and high levels of ELS show deficits in positive feedback sensitivity and reward learning in the probabilistic reversal learning task that are distinct from depressed patients. These deficits may be relevant to increased depression vulnerability.

neuroscience↗