Individual behavioral and neurochemical markers of unadapted decision-making processes in healthy inbred mice

Abstract

One of the hallmarks of decision-making processes is the inter-individual variability between healthy subjects. These behavioral patterns could constitute risk factors for the development of psychiatric disorders. Therefore, finding predictive markers of safe or risky decision-making is an important challenge for psychiatry research. We set up a mouse gambling task (MGT)—adapted from the human Iowa gambling task with uncertain contingencies between response and outcome that furthermore enables the emergence of inter-individual differences. Mice (n = 54) were further individually characterized for locomotive, emotional and cognitive behavior. Individual basal rates of monoamines and brain activation after the MGT were assessed in brain regions related to reward, emotion or cognition. In a large healthy mice population, 44 % showed a balanced strategy with limited risk-taking and flexible choices, 29 % showed a safe but rigid strategy, while 27 % adopted risky behavior. Risky mice took also more risks in other apparatus behavioral devices and were less sensitive to reward. No difference existed between groups regarding anxiety, working memory, locomotion and impulsivity. Safe/rigid mice exhibited a hypoactivation of prefrontal subareas, a high level of serotonin in the orbitofrontal cortex combined with a low level of dopamine in the putamen that predicted the emergence of rigid behavior. By contrast, high levels of dopamine, serotonin and noradrenalin in the hippocampus predicted the emergence of more exploratory and risky behaviors. The coping of C57bl/6J mice in MGT enables the determination of extreme patterns of choices either safe/rigid or risky/flexible, related to specific neurochemical and behavioral markers.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-016-1192-2) contains supplementary material, which is available to authorized users.

Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain

“…The present findings provide further support of a role for vitamin D in serotonin synthesis and metabolism in the developing brain. Furthermore, decreased cortical serotonergic function has been associated with impaired cognitive flexibility in adult mice (Pittaras et al, 2016) and increase impulsivity in humans (Campus et al, 2016). Serotonergic cell bodies, located in the raphe nuclei of the brainstem, primarily project to the frontal cortex and striatum (Chung et al, 2010).…”

Gambling disorder: an integrative review of animal and human studies

“…Additionally, nonoperant‐based tasks have been developed and used in rats and mice, which measure choice behavior with a multiarm maze . In one version of this paradigm called the mouse gambling task, each arm of the maze offers an immediate smaller reward (one or two sugar pellets) and then a subsequent larger reward (three to five sugar pellets) or an equivalent “nonreward,” which was nonpalatable quinine pellets, with probabilities ranging from 0.05 to 0.9 …”

“…48 In one version of this paradigm called the mouse gambling task, each arm of the maze offers an immediate smaller reward (one or two sugar pellets) and then a subsequent larger reward (three to five sugar pellets) or an equivalent "nonreward," which was nonpalatable quinine pellets, with probabilities ranging from 0.05 to 0.9. 53 This latter mouse paradigm is interesting because it includes the receipt of nonpalatable pellets instead of the absence of the reward plus a time-out, which is given in the rGT and mIGT. However, in some cases, rats are excluded if they consume the nonpalatable quinine pellets, limiting the benefit of this additional nonreward.…”

Modeling decision-making under uncertainty: a direct comparison study between human and mouse gambling data

“…These data illustrate a behavioral continuum with overlap in choice strategies between human physiological and pathological conditions. Interestingly, animal versions of the IGT have been developed, with species appropriate adjustments, to assess DM in a design comparable to humans [8][9][10][11][12][13][14][15][16] . For example, in rodent gambling tasks the decks of cards have been replaced by mazes or operant chambers suited with different options of varying outcomes.…”

“…Similar to human studies, lesioned rodents perform suboptimally in adapted IGT versions, as well as they show delayed DM compared to healthy individuals 18,19 . For the majority of healthy rodents, an improvement of performances is observed as the task progresses and individuals commonly cluster in three subpopulations reflecting variable choice strategies 12,14,20 . Good DM individuals quickly develop a strong preference for the advantageous options, while poor DM individuals display the worst performances, either not showing any preference for neither advantageous nor disadvantageous options, or displaying a long-term preference for the disadvantageous ones.…”