Biology subjects

Grissom, N. M.

Publications and source records attributed to Grissom, N. M..

4 recordsLinked to original sources

bioRxiv2023

Dopamine and norepinephrine differentially mediate the exploration-exploitation tradeoff

The catecholamines dopamine (DA) and norepinephrine (NE) have been implicated in neuropsychiatric vulnerability, in part via their roles in mediating the decision making processes. Although the two neuromodulators share a synthesis pathway and are co-activated, they engage in distinct circuits and roles in modulating neural activity across the brain. However, in the computational neuroscience literature, they have been assigned similar roles in modulating the exploration-exploitation tradeoff. Revealing how each neuromodulator contributes to this explore-exploit process is important in guiding mechanistic hypotheses emerging from computational psychiatric approaches. To understand the differences and overlaps of the roles of dopamine and norepinephrine in mediating exploration, a direct comparison using the same dynamic decision making task is needed. Here, we ran mice in a restless bandit task, which encourages both exploration and exploitation. We systemically administered a nonselective DA antagonist (flupenthixol), a nonselective DA agonist (apomorphine), a NE beta-receptor antagonist (propranolol), and a NE beta-receptor agonist (isoproterenol), and examined changes in exploration within subjects across sessions. We found a bidirectional modulatory effect of dopamine receptor activity on exploration - increasing dopamine activity decreased exploration and decreasing dopamine activity increased exploration. The modulation of exploration via beta-noradrenergic activity was mediated by sex. Computational model parameters revealed that dopamine modulation affected exploration via decision noise and norepinephrine modulation via outcome sensitivity. Together, these findings suggested that the mechanisms that govern the transition between exploration and exploitation are sensitive to changes in both catecholamine functions and revealed differential roles for NE and DA in mediating exploration. Significance StatementBoth dopamine (DA) and norepinephrine (NE) has been implicated in the decision making process. Although these two catecholamines have shared aspects of their biosynthetic pathways and projection targets, they are thought to exert many core functions via distinct neural targets and receptor subtypes. However, the computational neuroscience literature often ascribes similar roles to these catecholamines, despite the above evidence. Resolving this discrepancy is important in guiding mechanistic hypotheses emerging from computational psychiatric approaches. This study examines the role of dopamine and norepinephrine on the explore-exploit tradeoff. By testing mice, we were able to compare multiple pharmacological agents within subjects, and examine source of individual differences, allowing direct comparison between the effects of these two catecholamines in modulating decision making.

animal behavior and cognition↗

bioRxiv2021

Sequential delay and probability discounting tasks in mice reveal anchoring effects partially attributable to decision noise

Delay discounting and probability discounting decision making tasks in rodent models have high translational potential. However, it is unclear whether the discounted value of the large reward option is the main contributor to variability in animals choices in either task, which may limit translatability to human discounting data. Male and female mice underwent sessions of delay and probability discounting in sequence to assess how choice behavior adapts over experience with each task. To control for "anchoring" (persistent choices based on the initial delay or probability), mice experienced "Worsening" schedules where the large reward was offered under initially favorable delay or probability conditions that became less favorable during testing, followed by "Improving" schedules where the large reward was offered under initially unfavorable conditions that improved over a session. During delay discounting, both male and female mice showed elimination of anchoring effects over training. In probability discounting, both sexes of mice continued to show some anchoring even after months of training. One possibility is that noisy action selection could contribute to these anchoring effects, rather than persistent fluctuations in value discounting. We fit choice behavior in individual animals using models that included both a value-based discounting parameter and a decision noise parameter that captured variability in choices deviating from value maximization. Changes in anchoring behavior over time were tracked by changes in our decision noise parameter, not the value parameter. Thus, changes in discounting behavior in mice can result from changes in exploration of the environment rather than changes in reward valuation.

animal behavior and cognition↗

bioRxiv2020

Sex differences in learning from exploration

Sex-based modulation of cognitive processes could set the stage for individual differences in vulnerability to neuropsychiatric disorders. While value-based decision making processes in particular have been proposed to be influenced by sex differences, the overall correct performance in decision making tasks often show variable or minimal differences across sexes. Computational tools allow us to uncover latent variables that define different decision making approaches, even in animals with similar correct performance. Here, we quantify sex differences in mice in the latent variables underlying behavior in a classic value-based decision making task: a restless 2-armed bandit. While male and female mice had similar accuracy, they achieved this performance via different patterns of exploration. Male mice tended to make more exploratory choices overall, largely because they appeared to get "stuck" in exploration once they had started. Female mice tended to explore less, but learned more quickly during exploration. Together, these results suggest that sex exerts stronger influences on decision making during periods of learning and exploration than during stable choices. Exploration during decision making is altered in people diagnosed addictions, depression, and neurodevelopmental disabilities, pinpointing the neural mechanisms of exploration as a highly translational avenue for conferring sex-modulated vulnerability to neuropsychiatric diagnoses.

animal behavior and cognition↗

bioRxiv2019

Divergent strategies for learning in males and females

A frequent assumption in value-based decision-making tasks is that agents make decisions based on the feature dimension that reward probabilities vary on. However, in complex, multidimensional environments, stimuli can vary on multiple dimensions at once, meaning that the feature deserving the most credit for outcomes is not always obvious. As a result, individuals may vary in the strategies used to sample stimuli across dimensions, and these strategies may have an unrecognized influence on decision-making. Sex is a proxy for multiple genetic and endocrine influences that can influence decision-making strategies, including how environments are sampled. In this study, we examined the strategies adopted by female and male mice as they learned the value of stimuli that varied in both image and location in a visually-cued two-armed bandit, allowing two possible dimensions to learn about. Female mice acquired the correct image-value associations more quickly than male mice, and they used a fundamentally different strategy to do so. Female mice constrained their decision-space early in learning by preferentially sampling one location over which images varied. Conversely, male strategies were inconsistent, changing frequently and strongly influenced by the immediate experience of stochastic rewards. Individual strategies were related to sex-gated changes in neuronal activation in early learning. Together, we find that in mice, sex is linked with divergent strategies for sampling and learning about the world, revealing substantial unrecognized variability in the approaches implemented during value-based decision-making.

animal behavior and cognition↗