The role of Akt1, a schizophrenia candidate gene, in the regulation of behavioral and electrophysiological responses in reward-based decision-making in mice
Date Issued
2016
Date
2016
Author(s)
Chen, Ching
Abstract
Accumulating evidence from human genetic studies and animal studies suggests that AKT1, a schizophrenia candidate gene, is involved in the pathogenesis of schizophrenia and dopamine-dependent behaviors. Recent findings also indicate that AKT1 plays an important role in the regulation of schizophrenia-related behaviors, methamphetamine-induced behavioral sensitization, goal-directed behavior, reward prediction error in decision-making, and striatal neuronal activity, particularly in Akt1-deficient mice. In this study, to further investigate the role of Akt1 in the regulation of probabilistic reward-based decision-making, male Akt1 heterozygous (HET) mutant mice and their wild-type (WT) littermate controls were used to perform Pavlovian-conditioned pairing and a 2-choice dynamic foraging task with different reward rates. Behavioral data of the Pavlovian-conditioned pairing revealed that there was no significant difference in the sign-tracking or goal-tracking behaviors between HET and WT mice. However, in the 2-choice dynamic foraging task, HET mice took fewer trials to consistently choose the high reward option compared to their WT controls. Trial-by-trial choice behaviors of mice were further analyzed to estimate parameters for reinforcement learning. Our model-fitting data revealed that HET mice had a higher learning rate but a lower choice consistency compared to WT controls. Based on these findings, in vivo local field potential recordings were conducted in the dorsomedial striatum of mice during different stages of the decision-making process in the dynamic foraging task. Our results revealed a genotypic difference in the power spectrum density (dB) of local field potentials at the baseline. The event-related potential data further indicated genotypic differences at different stages of the decision-making process in different sections of reward rate of the dynamic foraging task. Our results collectively suggest that Akt1 deficiency can result in aberrant electrophysiological responses as well as abnormal reward prediction error signaling and reward learning during decision-making. Furthermore, our findings implicate the contribution of AKT1 deficiency and consequential neural abnormality in the dorsomedial striatum in the alteration of aberrant reward learning and reward prediction error signaling. Findings from this study shed light on our understanding of the role of Akt1 in reward-based decision-making and the involvement of this gene in the pathogenesis of schizophrenia.
Subjects
schizophrenia
motivational salience
reinforcement learning
Pavlovian-conditioned learning
2-choice dynamic foraging task
reward prediction error
Type
thesis
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