額葉紋狀體與額葉海馬體迴路功能性破壞對區辨性增強低頻反應操作式制約行為的影響

Abstract

在大腦掌管的高階認知功能中，前額葉、紋狀體，和海馬迴等多個腦區共 同針對衝動控制和時間感知這兩個功能扮演著重要角色。而在操作式制約行為 中，區辨性低反應頻率增強模式作業 (Differential Reinforcement of Low-rate Response task; DRL)被認為需要涉及上述兩個認知歷程。然而，過去對於此些腦 區的研究主要是使用消融、興奮性毒素破壞、或藥理方式所進行單一或雙側破 壞腦區的方式，很少有研究運用功能性連結破壞的方法探索衝動行為的神經機 制。本研究透過功能性連結破壞方法探討前額葉中兩個子腦區的連結、前額葉- 紋狀體、前額葉-伏隔核，和前額葉-海馬迴的神經連結機制對 DRL 衝動行為的 影響。實驗 1 針對外側眼眶前額葉(lateral orbitofrontal cortex; lOFC)與內側前 額葉(medial prefrontal cortex; mPFC)之間的功能聯繫進行破壞。實驗 2 則針 對外側眼眶前額葉與基底核或海馬迴進行功能性破壞。實驗 2-1 針對 lOFC 與背 側紋狀體(dorsal striatum; DS)，實驗 2-2 為 lOFC 與伏隔核(Nucleus accumbens; NAc)，以及實驗 2-3 為 lOFC 和海馬迴(Hippocampus; HIP)等三連結進行功能性破壞。實驗 3 則針對 mPFC 與 NAc 之間的連接進行了功能性破壞。然而，因連結破壞的實驗方式可能在學習階段的不同時間發生，因此本研 究測量了學習的不同階段，包含 DRL 10 秒與 DRL 15 秒的習得，DRL 15 秒消 除，與 DRL 15 秒再習得。研究結果顯示，在針對 lOFC-DS 連接迴路操弄的實 驗中，功能性破壞組在再習得階段的表現優於實驗控制組，其他階段則無此影 響。而在針對 lOFC-NAc 連接迴路操弄的實驗中，功能性破壞組則在習得 DRL 10 秒與 DRL 15 秒的表現較控制組差。然而在針對 lOFC-mPFC、lOFC-HIP 和 mPFC-NAc 這三個迴路操弄的研究中沒有組間的差異。綜合以上結果，實驗支 持皮質-紋狀體間的神經網絡參與衝動行為，並有助於實驗者對不同學習階段的 DRL 作業在行為抑制相關的時間感知中進行更深入的了解。

In the brain, the prefrontal, striatal, and hippocampal areas together are important for high-level cognition functions, including impulsive control and timing. Operant behavior trained by differential reinforcement of low-rate response (DRL) schedule of reinforcement requires these two processes. Previous studies investigated the functions of these brain areas using aspiration, excitotoxic lesion, or pharmacological treatment mainly through a manner of bilateral interventions, few studies applied the functional disconnection approach to explore the neural substrates of impulsive action. This study evaluated the roles of fronto-striatal and fronto-hippocampal circuits on DRL behavior via the approach of functional disconnection. Experiment 1 manipulated the functional disconnection between the lateral orbitofrontal cortex (lOFC) and medial prefrontal cortex (mPFC). Experiment 2 intervened the lOFC connecting to the dorsal striatum (DS; Experiment 2-1), to the nucleus accumbens (NAc; Experiment 2-2), and to the hippocampus (HIP; Experiment 2-3). And, Experiment 3 manipulated the functional disconnection between the mPFC and NAc. In consideration of the potential impacts of disconnection lesions that could affect distinct processes in different learning stages. Behavioral assessments were conducted in the acquisition of DRL 10s and DRL 15s which were followed by the extinction and spontaneous recovery. The results showed that rats with disconnection lesions of lOFC-DS performed better in the recovery stage than those with control lesions, but had no impact on the other stages. Moreover, rats with disconnection lesions of lOFC- NAc disrupted the acquisition of DRL 10s and DRL 15s. No significant influence was produced by the functional disconnection of lOFC-mPFC, lOFC-HIP, or mPFC-NAc. Together, the current data are in general agreement with the notion of the cortico- striatal circuit involved in impulsive action and provide insights of timing associated with behavioral inhibition in the acquisition of DRL behavior at different learning stages.