Augmented prefrontal acetylcholine release during challenged attentional performance

Augmented prefrontal acetylcholine release during challenged attentional performance
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DOI:
10.1093/cercor/bhi079
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发表时间:
2006-01-01
期刊:
影响因子:
3.7
通讯作者:
Sarter, M
Sarter, M
中科院分区:
医学2区
文献类型:
--
作者:
Kozak, R;Bruno, JP;Sarter, M

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先前的研究表明,注意力的表现取决于皮质胆碱能输入系统的完整性,并且这种表现与皮质乙酰胆碱(ACh)释放的增加有关。本实验验证了双侧基底前脑输注NMDA受体拮抗剂dl -2-氨基-5-磷酸戊酸(APV)引起的注意障碍与性能相关的乙酰胆碱释放增加的衰减有关的假设。大鼠接受持续注意力任务训练,并配备三根导管,用于双侧输注NMDA受体拮抗剂APV (0,3,20 nmol),并将透析探针插入内侧前额叶皮层(mPFC)。APV或载具在完成第一批试验后远程注入。在第一个阶段,注意力表现与乙酰胆碱外排增加140%相关。注射APV降低了动物检测信号的能力,增强了注射前观察到的乙酰胆碱外排的增加。这些数据表明,注意力表现水平与mPFC乙酰胆碱释放增加之间存在分离。假设mPFC胆碱能传递的增强与表现相关,可以调节在具有挑战性的条件下保持表现所需的注意力“努力”需求的增加。
Previous research has demonstrated that attentional performance depends on the integrity of the cortical cholinergic input system and that such performance is associated with increases in cortical acetylcholine (ACh) release. The present experiment tested the hypothesis that the attentional impairments produced by bilateral basal forebrain infusions of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) are associated with attenuation of performance-associated increases in ACh release. Rats were trained in a sustained attention task and equipped with three guide cannula for the bilateral infusion of the NMDA receptor antagonist APV (0, 3, 20 nmol) and for the insertion of a dialysis probe into the medial prefrontal cortex (mPFC). APV or vehicle was infused remotely following completion of the first of five blocks of trials. During the first block, attentional performance was associated with a 140% increase in ACh efflux. Infusions of APV decreased the animals' ability to detect signals and augmented the increases in ACh efflux observed prior to infusions. These data indicate a dissociation between levels of attentional performance and increases in mPFC ACh release. Augmentation of performance-associated increases in mPFC cholinergic transmission is hypothesized to mediate the increased demands on attentional 'effort' that are required to maintain performance under challenging conditions.