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抑制 PKMζ 揭示了背外侧纹状体和背内侧纹状体储存了支持适应性行为所需的不同记忆。

Inhibiting PKMζ reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior.

机构信息

Department of Neuroscience and Psychology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.

出版信息

Learn Mem. 2012 Jun 20;19(7):307-14. doi: 10.1101/lm.025148.111.

DOI:10.1101/lm.025148.111
PMID:22723053
Abstract

Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.

摘要

有证据表明,纹状体的两个区域对工具性反应选择有不同的支持作用。背内侧纹状体(DMS)被认为支持期望介导的动作,而背外侧纹状体(DLS)被认为支持习惯。目前尚不清楚这些区域是存储与任务相关的信息,还是只是协调其他大脑区域对这些解决方案的学习和保留。为了解决这个问题,我们开发了一个双杠杆同时可变间隔强化操作性条件反射任务,并使用它来评估训练大鼠对关联变化的敏感性。与这两个区域对动作和习惯有不同贡献的观点一致,在关联变化前将 NMDA 拮抗剂 DL-AP5 注入 DMS 会损害大鼠的表现,但注入 DLS 会增强表现。为了确定这些区域是否支持记忆内容,我们首先在偏置同时性方案(杠杆 1:VI 40"和杠杆 2:VI 10")上训练大鼠。为了“擦除”存储在纹状体中的记忆内容,在这种训练之后,我们抑制了假定的记忆维持蛋白激酶 C 同工酶蛋白激酶 Mζ(PKMζ)。将zeta 抑制肽(ZIP)注入 DLS 增强了大鼠适应关联变化的能力,而将其注入 DMS 则产生相反的效果。在 ZIP 注射前 1 小时将 GluR2(3Y) 注入 DMS 可防止 ZIP 损害大鼠对关联变化的敏感性。这些结果支持了这样的假设,即 DMS 存储支持动作所需的信息,而 DLS 存储支持习惯所需的信息。

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