Biology subjects

Wilod Versprille, L. J. F.

Publications and source records attributed to Wilod Versprille, L. J. F..

4 recordsLinked to original sources

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

Modulatory effects of α7-nicotinic cholinergic receptors on perceptual sensitivity in a visual signal detection task

RationaleCholinergic signalling is critical for attentional control and signal detection, yet the contribution of specific acetylcholine receptor (AChR) subtypes remains poorly understood. Although the 7 nicotinic AChR (nAChR) holds promise as a target for cognition-enhancing therapy, clinical findings to date have been inconsistent. ObjectiveTo investigate the effects of putative cognitive enhancing drugs, including those targeting cholinergic transmission and 7 nAChRs on a visual signal detection task (SDT). MethodsMale and female Sprague Dawley rats were trained on an SDT. Cholinergic transmission was probed systemically with nicotinic and muscarinic receptor antagonists (mecamylamine and scopolamine), a cholinesterase inhibitor (galantamine), an M4-AChR positive allosteric modulator (PAM; VU0467154), an 7 nAChR antagonist (MLA), an 7 nAChR PAM (CCMI), and an 7 nAChR partial agonist (SSR-180,711). Dopaminergic transmission was probed using the catechol-O-methyltransferase (COMT) inhibitor, tolcapone. A novel, trial-level signal detection theory-based generalised linear mixed-effects model (SDT-GLMM) was used to index response bias and perceptual sensitivity (d'), the latter reflecting subjects ability to discriminate signal from noise. ResultsMecamylamine profoundly impaired SDT performance across all measures. Galantamine significantly improved d' at moderate doses but not when a distractor was present. MLA uniquely produced dose-dependent improvements in d' that were preserved under distraction. In contrast, positive allosteric modulation and agonism of 7 nAChRs impaired task performance. Scopolamine, VU0467154, and tolcapone had no consistent or interpretable effects on signal detection. ConclusionsThis work demonstrates that 7 nAChR modulation bidirectionally and dose-dependently regulates perceptual sensitivity, irrespective of attentional distraction. These findings have implications for targeted cognitive enhancement in disorders of attention.

neuroscience↗

bioRxiv2026

Detrimental effects of atomoxetine on visual signal detection in rats: Comparison with ADHD psychomotor stimulant drugs

RationaleAttention-deficit/hyperactivity disorder (ADHD) is associated with executive dysfunction involving inattention and impulsivity, with evidence of disrupted functional expression of the dopamine and noradrenaline transporters. ObjectiveWe investigated the dose-dependent modulation of anti-ADHD drugs on selective and sustained visual attention in low-, mid-and high-attention phenotypes. Two mathematical approaches, signal detection theory and theory of visual attention were applied to further characterise the effects and mechanisms. MethodsRats were trained to detect and respond to the presence or absence of a visual target to obtain food reward on a signal detection task. After attentional performance stabilised, the indirect catecholamine agonist, d-amphetamine (0.1; 0.2; 0.4 mg/kg), the dopamine (DA) and noradrenaline (NA) reuptake inhibitor methylphenidate (0.3; 1; 3 mg/kg), and the NA reuptake inhibitor atomoxetine (0.1; 0.3; 1 mg/kg), were administered systemically. ResultsLow-dose d-amphetamine produced baseline-dependent effects on attention, improving target discrimination only in rats with lower attentive performance, whereas methylphenidate did not significantly improve attention but increased guessing. In contrast, low-dose atomoxetine selectively impaired attention in low-attentive subjects, whereas high-dose atomoxetine generally impaired discrimination performance. All three drugs had expected effects on motor response output. ConclusionsAs well as demonstrating baseline-dependent effects of amphetamine on visual attention, the findings for methylphenidate and atomoxetine suggest important, apparently opposing effects on visual signal detection performance produced via blockade of the DA and NA transporters. The deleterious effects of atomoxetine on performance were especially noteworthy in view of its use as a treatment in ADHD.

animal behavior and cognition↗

bioRxiv2025

Dopamine Dynamics in the Nucleus Accumbens Reflect Confidence in Detecting the Occurrence and Non-Occurrence of Visual Signals in Perceptual Decision-Making

Dopamine (DA) is critically involved in processes such as reward anticipation, attention, and decision - making. The present study examined the temporal dynamics of phasic DA transients in the nucleus accumbens core (NAcC) during a visual decisional task based on signal detection theory, using the fluorescent DA sensor dLight1.3b. During the decision-making phase, DA transients in the NAcC encoded real-time outcome expectancy, apparently reflecting the confidence of rats in their choices. Reward prediction errors (RPEs) emerged following reward delivery and omission and were amplified under conditions of increased uncertainty, produced either by degrading the visual target or introducing interfering distraction. Moreover, DA transients were elicited on both visual signal and no-signal trials. These findings demonstrate that DA fluctuations in the NAcC reflect the RPE that incorporates confidence and levels of uncertainty, emphasizing an involvement of nucleus accumbens DA in adaptive decision-making.

neuroscience↗