Biology subjects

Stupart, O.

Publications and source records attributed to Stupart, O..

3 recordsLinked to original sources

bioRxiv2026

Maternal separation recalibrates prefrontal mitochondrial function and protects against stress-induced negative cognitive bias

Ambiguity represents a form of uncertainty in which outcome probabilities cannot be explicitly learned, making decisions dependent on emotional states and cognitive biases. Early-life stress (ELS) increases the risk of adverse mental and physical health outcomes and alters affective processing and learning. ELS may thus affect how ambiguous information is processed, which may depend on interactions with adulthood stress (AS) and mechanistically on bioenergetic mechanisms mediated by top-down cognitive control systems within the prefrontal cortex (PFC). The present study investigated the effects of AS in rats exposed to early maternal separation (MS), a rodent model of ELS, on a task assessing cognitive bias, together with putatively accompanying alterations in PFC mitochondrial function. Cognitive bias was assessed using an ambiguous cue task (ACT) in MS and non-separated control rats tested at baseline and following repeated unpredictable mild stress during adulthood. MS did not affect baseline cognitive bias but increased response latencies. Following AS, control animals showed a significant negative shift in cognitive bias, whereas MS animals were resistant to this shift. MS was also associated with greater PFC mitochondrial respiratory capacity and uncoupling of oxidative phosphorylation following AS. These findings suggest that ELS is associated with a recalibrated phenotype that buffers against the affective consequences of later stress. Enhanced PFC mitochondrial bioenergetics may underlie this resilience, highlighting the importance of developmental context in shaping affective-cognitive responses to stress.

neuroscience↗

bioRxiv2026

Impacts and interactions of stress, noradrenaline and serotonin signalling on probabilistic reversal learning

RationaleEarly life stress (ELS) is acknowledged to underlie cognitive and emotional abnormalities linked to stress-related mood disorders. ELS can lead to persistent biases in how uncertain feedback is processed to affect the flexibility of decision-making. Objectives(1) To investigate the effects of ELS on the flexibility of rats trained on a serial probabilistic reversal learning (PRL) task involving spurious positive and negative feedback. (2) To elucidate the involvement of the stress hormone corticosterone and the noradrenergic and serotonergic systems in modulating how ELS affects PRL. MethodsMale and female rats were intermittently separated from maternal care on postnatal days five to nineteen, inclusively. As adults, the same rats were trained on a deterministic reversal learning task involving certain rewarded or non-rewarded outcomes followed by a PRL task where correct and incorrect responses were rewarded on 80% and 20% of trials, respectively. Dose-dependent effects of the beta-blocker, propranolol, selective serotonin reuptake inhibitor, citalopram and corticosterone were subsequently determined. ResultsELS resulted in an increased responsivity to feedback, specifically in males making more win-stay responses following a reward, that was associated with an increased punishment learning rate. In both control and MS rats, propranolol increased feedback sensitivity, but delayed updating following a rule switch. In contrast, neither citalopram nor corticosterone significantly affected reversal learning. ConclusionsELS is sufficient to cause persistent changes in how feedback is processed by male rats on a reversal learning task. Activation of beta-adrenergic receptors may be necessary for updating learned associations during decision-making involving uncertain feedback.

neuroscience↗

bioRxiv2026

Expression levels of α5 subunit-containing GABA-A receptors in the prelimbic cortex are associated with visual perceptual learning

Perceptual learning is a dynamic process involving the acquisition and integration of sensory information necessary for adaptive decision making. Resolving the neural basis of perceptual learning may have relevance for our understanding of schizophrenia and other neurodevelopmental disorders that implicate impaired perceptual acuity. We developed a novel touchscreen task that utilizes orientation discrimination and variable attentional load to elucidate the perceptual and attentional components of visual perceptual learning (VPL) in male and female rats. Based on previous evidence we hypothesised that individual variation in VPL may depend in part on inhibitory neurotransmission mediated by {gamma}-amino butyric acid (GABA). Segregating subjects based on poor and good learning after task pretraining revealed dose-dependent improvements in VPL in poor learners following the administration of an 5 subunit specific GABA-A (GABRA5) positive allosteric modulator (Alogabat) and a GABA-B agonist (R-baclofen) early in learning. Poor VPL performance was associated with significantly reduced GABRA5 mRNA expression in dorsal regions of the prefrontal cortex (PFC), notably the prelimbic cortex. Decreased GABRA5 expression in this region was co-localized to somatostatin- and parvalbumin-expressing interneurons. These findings reveal a potential link between GABRA5 expression in selective PFC populations of inhibitory interneurons and the speed and acuity of VPL. Significance statementCortical inhibitory microcircuits underlie visual perceptual learning (VPL) and may contribute to altered perceptual learning in neurodevelopmental disorders. However, the mechanisms underlying VPL are poorly understood. This study implemented a translationally relevant touchscreen task to assess visual perception and attention. We report that 5-subunit containing GABA-A receptors (GABRA5) are decreased in expression in the prelimbic subregion of the prefrontal cortex in animals that are slower to acquire the VPL task compared with animals showing superior VPL. We also report that VPL can be improved in a subset of poor learning animals by a positive allosteric modulator of GABRA5. These findings suggest that GABRA5 may be a potential therapeutic target to improve visual perception in schizophrenia and other neurodevelopmental disorders.

neuroscience↗