Differential involvement of M1-type and M4-type muscarinic cholinergic receptors in the dorsomedial striatum in task switching
Differential involvement of M1-type and M4-type muscarinic cholinergic receptors in the dorsomedial striatum in task switching
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DOI：
10.1016/j.nlm.2007.06.005
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发表时间：
2008-02-01
影响因子：
2.7
通讯作者：
Ragozzino, Michael E.
中科院分区：
文献类型：
--
作者：
McCool, Martha F.;Patel, Sima;Ragozzino, Michael E.
先前的实验已经证明，当条件需要改变策略时，大鼠的背内侧纹状体是一个在学习中起关键作用的大脑区域。进一步的证据表明，该脑区的毒蕈碱胆碱能受体支持行为反应的适应。目前尚不清楚背内侧纹状体中的特定毒蕈碱受体亚型是否有助于反应模式的灵活转变。本实验研究是否阻断M1型和/或M4型胆碱能受体在背内侧纹状体的基础位置反转学习。实验1研究了M1型毒蕈碱胆碱能拮抗剂的作用，毒蕈碱毒素7（MT-7）注入背内侧纹状体的位置获得和逆转学习。实验二探讨了纹状体背内侧区注射M4型胆碱能拮抗剂毒蕈碱毒素3（MT-3）对位置获得和逆转学习的影响。所有测试均在两个连续阶段的改良十字迷宫中进行。双侧注射MT-7到背内侧纹状体1或2微克，但不是0.05微克受损的位置反转学习。错误的分析表明，MT-7在1和2 μ g显着增加回归错误，但不持久的错误。注射MT-7 2微克到背内侧纹状体前收购的地方没有影响学习。实验2显示，背内侧纹状体注射MT-3（0.05，1或2 μ g）不影响位置获取或逆转学习。研究结果表明，激活M1型毒蕈碱胆碱能受体在背内侧纹状体，但不是M4型毒蕈碱胆碱能受体促进灵活的转变反应模式，保持或学习一个新的选择模式，一旦选择。(C)2007爱思唯尔公司All rights reserved.
Previous experiments have demonstrated that the rat dorsomedial striatum is one brain area that plays a crucial role in learning when conditions require a shift in strategies. Further evidence indicates that muscarinic cholinergic receptors in this brain area support adaptations in behavioral responses. Unknown is whether specific muscarinic receptor subtypes in the dorsomedial striatum contribute to a flexible shift in response patterns. The present experiments investigated whether blockade of M1-type and/or M4-type cholinergic receptors in the dorsomedial striatum underlie place reversal learning. Experiment 1 investigated the effects of the M1-type muscarinic cholinergic antagonist., muscarinic-toxin 7 (MT-7) infused into the dorsomedial striatum in place acquisition and reversal learning. Experiment 2 investigated the effects of the M4-type muscarinic cholinergic antagonist, muscarinic-toxin 3 (MT-3) injected into the dorsomedial striatum in place acquisition and reversal learning. All testing occurred in a modified cross-maze across two consecutive sessions. Bilateral injections of MT-7 into the dorsomedial striatum at 1 or 2 mu g, but not 0.05 mu g impaired place reversal learning. Analysis of the errors revealed that MT-7 at 1 and 2 mu g significantly increased regressive errors, but not perseverative errors. An injection of MT-7 2 mu g into the dorsomedial striatum prior to place acquisition did not affect learning. Experiment 2 revealed that dorsomedial striatal injections of MT-3 (0.05, 1 or 2 mu g) did not affect place acquisition or reversal learning. The findings suggest that activation of M1-type muscarinic cholinergic receptors in the dorsomedial striatum, but not M4-type muscarinic cholinergic receptors facilitate the flexible shifting of response patterns by maintaining or learning a new choice pattern once selected. (C) 2007 Elsevier Inc. All rights reserved.