台大心理系

Schizophrenia is a severe neuropsychiatric disorder in which cognitive impairment features prominently. Accumulating evidence from human genetic studies suggests that multiple susceptibility genes might contribute to the pathogenesis of schizophrenia, including AKT1 (protein kinas B α), a key signaling kinase intermediate downstream of dopamine D2 receptor. Alterations of dopaminergic transmission have been implicated in the pathogenesis of schizophrenia and patients with schizophrenia also show worse performance than healthy controls in many decision-making tasks. Recent finding further revealed that Akt1 might play a crucial role in the modulation of reward-based decision making, especially in the striatum. However, so far, the importance of Akt1 in reward-based decision making and its specific role in the dorsomedial striatum (DMS) during this process remain elusive. To this end, we examined the role of Akt1 in a probabilistic two-choice foraging task and the relationship between electrophysiological properties in the DMS and behavioral performance in Akt1 heterozygous mutant (Akt1^+/-) mice and their wild-type littermates. In this task, each food-deprived mouse had to discover which choice has a higher reward rate by trial and error and to maximize the total amount of reward. Once the pre-set criterion was achieved, each mouse moved on to reversal phase and the reward rates of the two choice arms were switched. Simultaneously, in vivo electrophysiological recording was conducted in the DMS of the mouse brain during the whole acquisition and reversal phases. Analysis of neural oscillations and behavioral model fitting were performed as well. Our results indicated that (1) Akt1^+/- mice required significantly fewer trials to achieve the criteria compared to their controls in both acquisition and reversal phases. (2) The evoked power in the DMS is time-locked while receiving the outcome of each choice. In the trials of no-reward outcomes, the evoked theta and gamma powers had a high correlation with their behavioral outcomes whereas no correlation was found in the trials of reward outcomes. (3) Taking advantage of a Bayesian approach to estimate the parameters in a modified reinforcement learning model, we found that Akt1^+/- mice have a higher learning rate in the no-reward outcomes compared to controls. Collectively, our results suggest that the neural oscillation in the DMS contributed to the learning rate which resulted in the differential behavioral performances in Akt1^+/- mice during decision making. Our emerging data provides further support to the importance of AKT1 in schizophrenia-related cognitive deficits that is certainly worth further investigation.