Biology subjects

Milton, A. L.

Publications and source records attributed to Milton, A. L..

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

The silence of the rewards: Non-reward cue suppresses cue-driven behaviour in pavlovian-instrumental transfer

Flexible reward-seeking relies upon an organisms integration of expectations about environmental cues with knowledge of actions that produce rewards, which is captured by pavlovian instrumental transfer (PIT). Although widely used to study motivation across species, rodent PIT paradigms differ from human tasks in lacking an active baseline for comparison. Here we adapted the full PIT paradigm to include a non-rewarded cue (CSO) as an active control with the aim of improving the translational relevance of the procedure. Despite robust pavlovian and instrumental learning, neither male nor female rats expressed outcome-specific PIT when the active baseline was present. The absence of PIT persisted even after instrumental extinction training prior to the test, though cue-driven magazine approaches remained elevated. Data obtained under these conditions may reflect protocol-dependent modulation by the amount of training, or strain-specific differences in motivational influence. Replicated across male and female cohorts, they identify boundary conditions where PIT appears less robust. This methodological adaptation advances the translational alignment between animal and human PIT paradigms and informs future investigations into the mechanisms of cue-motivated behaviour.

animal behavior and cognition↗

bioRxiv2018

A re-examination of responding on ratio and regulated-probability interval schedules

The higher response rates observed on ratio than on matched interval reward schedules has been attributed to the differential reinforcement of longer inter-response times (IRTs) on the interval contingency. Some data, however, seem to contradict this hypothesis, showing that the difference is still observed when the role of IRT reinforcement is neutralized by using a regulated-probability interval schedule (RPI). Given the mixed evidence for these predictions, we re-examined this hypothesis by training three groups of rats to lever press under ratio, interval and RPI schedules across two phases while matching reward rates within triads. At the end of the first phase, the master ratio and RPI groups responded at similar rates. In the second phase, an interval group yoked to the same master ratio group of the first phase responded at a lower rate than the RPI group. Post-hoc analysis showed comparable reward rates for master and yoked schedules. The experienced response-outcome rate correlations were likewise similar, and approached zero as training progressed. We discuss these results in terms of dual-system theories of instrumental conditioning.

animal behavior and cognition↗