Biology subjects

Giglio, E.

Publications and source records attributed to Giglio, E..

4 recordsLinked to original sources

bioRxiv2025

16p11.2 duplication shows early male-biased impacts on reward learning, but NMDA receptor antagonism reduces optimal choice selection in both wildtypes and 16p11.2 duplication

Rationale16p11.2 duplication is associated with numerous neuropsychiatric conditions at a genome-wide level, including psychosis. Mice modeling 16p11.2 duplication may provide important insights into cognitive risk factors, in particular in reward-guided decision making. NMDAR function has also been implicated in psychosis phenotypes, but whether these phenotypes differ by genetic risk factor is unknown. ObjectivesWe aimed to: 1) identify sex and genotype differences in early operant training and two-arm spatial restless bandit task performance; 2) examine the effects of an NMDAR antagonist on task performance and strategy across genotypes. Methods16p11.2 duplication and wildtype mice completed a series of training schedules of escalating difficulty followed by bandit tasks. MK-801 and saline were administered in alternating sessions prior to later bandit task performance. ResultsLarge sex differences in early operant training revealed some male-biased impacts of 16p11.2 duplication, contingent on training schedule difficulty. Once on the two-arm spatial restless bandit task, 16p11.2 duplication was no longer a strong contributor to decision making. However, MK-801 decreased the tendency to stay with a rewarded choice, lowered the probability of selecting the highest rewarded option, and decreased the influence of prior outcomes on choice. ConclusionsThe male-biased vulnerability in early operant training suggests that strategies for learning early schemas or in novel environments may be impacted by 16p11.2 duplication in males. In contrast, NMDAR are influential in the ability to flexibly switch between choices, and disrupting this function significantly impairs decision making in all animals.

animal behavior and cognition↗

bioRxiv2025

Sex-biased computations underlying differential set shift performance in mice

Cognitive flexibility can be defined as the ability to adaptively shift between choices or strategies based on environmental feedback and it is disrupted in numerous neuropsychiatric conditions. Individual differences in the computations supporting cognitive flexibility are poised to reveal mechanisms of neuropsychiatric risk and resilience. One critical variable well known to influence individual differences in neuropsychiatric risk is sex. While previous research has identified sex differences in value based decision making in mice, whether sex reflects a major source of variation in cognitive flexibility remains unknown. To directly assess sex-biased individual differences in cognitive flexibility, we developed a novel touchscreen Set Shift task that permits robust and continuous testing in mice. Using this task, we discovered that female mice completed significantly more rule shifts with fewer errors than males. We next employed a suite of computational models that revealed sex-biased individual differences in the computations underlying cognitive flexibility. Overall, our results suggest that following rule shifts, female mice learn the new rule faster and commit to exploiting rule choices sooner compared to males - sometimes because they commit to multiple rules simultaneously. This suggests that increased choice stability in female rodents enhances commitment to a strategy during periods of uncertainty and directly contributes to increased rule shifting. This supports the counterintuitive conclusion that a high degree of stable choice is a strong requirement for enhanced cognitive flexibility in the Set Shift task, one of the gold standard cognitive flexibility tasks.

animal behavior and cognition↗

bioRxiv2025

Nitrogen and oxygen isotope effects during enzymatic nitrate reduction in vitro and by natural lake water consortia

Nitrate (NO3-) isotope ratios are useful indicators for nitrogen (N)-transformation processes if the associated isotope effects and their environmental controls are well-constrained. The NO3- isotope effects in natural environments may depend on the type of dissimilatory nitrate reductases involved and the degree of isotopic overprinting via NO3- regeneration. We measured the coupled N and oxygen (O) isotope effects of NO3- reduction in anoxic incubation experiments with laboratory cultures (Pseudomonas sp. and Escherichia coli) harboring different nitrate reductase enzymes (Nar and/or Nap) as well as with natural freshwater consortia from Lake Lugano (Switzerland) and Lake La Cruz (Spain). For comparison, isotope effects were also evaluated through coupled N and O isotope measurements in the redox transition zone of Lake Lugano North Basin. Incubation-based Rayleigh model N isotope effects ({varepsilon}N) were variable, ranging from 9 to 30{per thousand}. In comparison, in situ {varepsilon}N values (5 to 14{per thousand}) estimated by the closed system model were lower, likely due to substrate limitation in the water column. Experiments with Pseudomonas sp. and E. coli cultures possessing Nar yielded N isotope effects of similar magnitudes and, consistent with previous data, robust {Delta}{delta}18O:{Delta}{delta}15N enrichment ratios of [~]0.9 - 1.0. Nitrate reduction by cultures possessing solely Nap led to lower {Delta}{delta}18O:{Delta}{delta}15N of [~]0.7. In anoxic incubations of lake water, where the effect of nitrification could be excluded, {Delta}{delta}18O:{Delta}{delta}15N values between 0.6 and 1.0 suggest "community activity" of both Nar and Nap. Interestingly, stimulation of lithotrophic nitrate reduction in incubations with amended NO3- + sulfide resulted in a {Delta}{delta}18O:{Delta}{delta}15N slope of 0.90 {+/-} 0.03 (standard error, SE), indicating Nar as the more dominant nitrate-reducing enzyme. On the contrary, stimulation of organotrophic nitrate reduction in NO3- + acetate amended incubations resulted in a significantly lower slope of 0.72 {+/-} 0.03 SE, suggesting a greater contribution by Nap. In contrast to the nitrate-reduction incubation experiments, the in situ {Delta}{delta}18O:{Delta}{delta}15N value of 1.36 {+/-} 0.14 SE observed in the Lake Lugano water column was unusually high for a freshwater environment, likely reflecting the superimposed effect of NO3- production by nitrification. Our study thus underscores that both variations in activity of Nar versus Nap during nitrate reduction, as well as isotopic overprinting by nitrate regeneration may impact ecosystem NO3- isotope dynamics in natural denitrifying environments.

microbiology↗

bioRxiv2024

Touchscreen response precision is sensitive to the explore/exploit tradeoff

The explore/exploit tradeoff is a fundamental property of choice selection during reward-guided decision making. In perceptual decision making, higher certainty decisions are more motorically precise, even when the decision does not require motor accuracy. However, while we can parametrically control uncertainty in perceptual tasks, we do not know what variables - if any - shape motor precision and reflect subjective certainty during reward-guided decision making. Touchscreens are increasingly used across species to measure choice, but provide no tactile feedback on whether an action is precise or not, and therefore provide a valuable opportunity to determine whether actions differ in precision due to explore/exploit state, reward, or individual variables. We find all three of these factors exert independent drives towards increased precision. During exploit states, successive touches to the same choice are closer together than those made in an explore state, consistent with exploit states reflecting higher certainty and/or motor stereotypy in responding. However, exploit decisions might be expected to be rewarded more frequently than explore decisions. We find that exploit choice precision is increased independently of a separate increase in precision due to immediate past reward, suggesting multiple mechanisms regulating choice precision. Finally, we see evidence that male mice in general are less precise in their interactions with the touchscreen than females, even when exploiting a choice. These results suggest that as exploit behavior emerges in reward-guided decision making, individuals become more motorically precise reflecting increased certainty, even when decision choice does not require additional motor accuracy, but this is influenced by individual differences and prior reward. These data uncover the hidden potential for touchscreen tasks in any species to uncover the latent neural states that unite cognition and movement.

animal behavior and cognition↗