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

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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.

Figures

  • Fig. 1 a Schematic representation of the MGT experimental design and picture of the maze. White circle represented food pellets and black circle quinine pellets. Advantageous choices gave access to one food pellet and then to three or four food pellets (18/20) or quinine pellets (2/20). Disadvantageous choices gave access to two food pellets and then to four or five food pellets (1/20) or quinine pellets (19/20). We distinguished advantageous choices from
  • Fig. 2 Inter-individual differences that emerged during the MGT. a Performances evolution during MGT for safe (n = 16, grey circle), average (n = 23, black square) and risky animals (n = 15, grey triangle). Safe and average groups differed from chance but not risky group (W safe, #p\ 0.05; average, *p\ 0.05). The three sub-groups differed from each other during the two last sessions (MW, §p\ 0.05). b Cumulative pellet consumption across sessions (addition of pellets obtained from the beginning for each session). Safe and average animals did not differ from each other but the three groups differed the three last sessions (KW, #p\ 0.05). c Rigidity score was calculated as the percentage of the more chosen arms during the two
  • Fig. 3 Individual behavioral characterization. a During the sucrose preference task, average (n = 23) and safe (n = 16) animals significantly preferred sucrose over water whereas risky mice (n = 14) did not differ from chance (W, *p\ 0.05). Safe and risky animals differed from each other (MW, #p\ 0.05). b Risky (n = 15) animals spent more time in the open arms of the elevated plus maze and did
  • Fig. 4 A. Relative quantification of fos reactivity (mean ± SEM) in the orbitofrontal cortex (OFC), amygdala (Amy), nucleus accumbens (NAcc), basolateral amygdala (BLA), prelimbic (PrL), infralimbic (IL), cingular cortex (Cg), caudate putamen, (CPu), insular cortex (CIns), hippocampus and motor cortex. c-fos quantification was expressed as a percentage of that measured in the control group
  • Fig. 5 Basal rates of serotonin (5-HT) (a–d) and dopamine (DA) (e– h) in the prelimbic (PrL), the insular cortex (CIns), orbitofrontal cortex (OFC), the hippocampus, the amygdala (Amy), the nucleus accumbens (NAcc) and the caudate putamen (CPu) for safe (n = 16), average (n = 20) and risky (n = 14) mice. Results are expressed as mean ± SEM for each group. *p\ 0.05 represented a significant

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APA

Pittaras, E., Callebert, J., Chennaoui, M., Rabat, A., & Granon, S. (2016). Individual behavioral and neurochemical markers of unadapted decision-making processes in healthy inbred mice. Brain Structure and Function, 221(9), 4615–4629. https://doi.org/10.1007/s00429-016-1192-2

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