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Altered Decision Behavior of Dopamine Receptor Knock-out Mice in a Free Binary Choice Task

초록/요약

Dopamine has been thought to play an important role in updating values according to reward prediction error by reinforcement learning theory, since the finding that phasic activity of midbrain dopamine neurons signals the difference between actual and predicted outcomes (reward prediction error). However, the extent and nature of dopamine roles in reward-based learning are still under debate. Specific roles of different dopamine receptor subtypes in this process are also unknown. To investigate roles of dopamine receptor subtypes in reward-based learning, I examined choice behavior of dopamine D1 and D2 receptor-knockout (D1R-KO and D2R-KO, respectively) mice in an instrumental learning task with progressively increasing reversal frequency and in a dynamic foraging task. Performance of D2R-KO mice was progressively impaired in an instrumental learning task as the frequency of reversal increased and profoundly impaired in a dynamic foraging task even with prolonged training, whereas D1R-KO mice showed only minor deficits in performance. Animals’ choice behavior in the dynamic foraging was better explained by hybrid model that included win-stay-lose-switch and reinforcement learning terms than by simple reinforcement learning alone. A hybrid model-based analysis revealed that D1R-KO mice showed the increased win-stay and uncertainty-based exploration, and D2R-KO mice also showed the increased win-stay, but at the same time, showed the impaired value updating and increased randomness in action selection which were detrimental to maximizing rewards in the dynamic foraging task. These results indicate that dopamine D2 receptors rather than D1 receptors are important in learning from past choice outcomes for optimizing choice strategy in a dynamic and uncertain environment.

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목차

I. INTRODUCTION 1
A. Reinforcement Learning 2
1. Dilemma of exploration and exploitation 4
2. Q-learning model as a model-free method 6
B. The dopaminergic system 7
1. Features of the dopamine system 7
2. Dopamine-mediating learning 14
C. Aim of the thesis 15
II. MATERIALS AND METHODS 18
A. Genetic information of subjects 18
B. Apparatus 19
C. Behavioral task 19
1. Reversal learning task 21
2. TAB task 21
D. Experimental groups 24
E. Analysis 27
1. Logistic regression 27
2. Computational models 28
3. Statistics 31
III. RESULTS 32
A. Behavioral performance 32
1. Reversal task 32
2. TAB task 35
B. Logistic regression analysis 39
C. Modeling 41
IV. DISCUSSION 54
A. Motor deficits in both D1R- and D2R-KO mice 54
B. Role of D2R in rapid adjustment of choice behavior 55
C. Learning from RPE 56
D. Value-dependent action selection 57
E. Win-stay 58
F. Uncertainty-driven exploration 59
G. Multiple roles of dopamine in reward effects 59
H. Model-free vs. Model-based RL 60
I. Future directions 61
V. CONCLUSION 63

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