Noradrenergic control of error perseveration in medial prefrontal cortex.
Noradrenergic control of error perseveration in medial prefrontal cortex.
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DOI：
10.3389/fnint.2012.00125
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发表时间：
2012
影响因子：
3.5
通讯作者：
Laubach M
中科院分区：
文献类型：
--
作者：
Caetano MS;Jin LE;Harenberg L;Stachenfeld KL;Arnsten AF;Laubach M
内侧前额叶皮质(MPFC)在行为变异、动作监测和抑制控制中起着关键作用。由于一系列与衰老相关的问题，mPFC的功能作用可能会随着寿命的延长而改变，包括树突状细胞退化、cAMP信号增加以及影响mPFC加工的神经调节剂效力的降低。MPFC中的一个关键神经递质是去甲肾上腺素。以前的研究已经报道了mPFC依赖任务对去甲肾上腺素能激动剂药物(如鸟嘌呤)的敏感性随年龄的变化。在这里，我们评估了育亨宾，一种α-2去甲肾上腺素能拮抗剂，在一组年轻和老年大鼠中的效果，在一个经典的空间工作记忆测试中(使用T迷宫)。老年大鼠(23-29个月)与年轻的动物(5-10个月)相比，育亨宾的剂量较小。为了确定药物是否作用于mPFC的α-2去甲肾上腺素能受体，以及它的作用是否与记忆引导能力有关，我们将育亨宾注入一组年轻大鼠的mPFC(6个月)。使用可操作的延迟反应任务。这项任务包括在记忆和刺激引导下对大鼠进行分组试验。育亨宾选择性地损害记忆引导的表现，并与错误持久力有关。在相同的部位注射麝香酚(一种GABA-A激动剂)也选择性地损害记忆引导能力，但不会导致错误坚持。基于这些结果，我们对去甲肾上腺素系统在延迟反应任务中的作用提出了几种可能的解释，包括对先前反应位置的编码、任务规则(即，使用Win-Stay策略而不是Win-Shift策略)和性能监控(例如，对结果的预期编码)。
The medial prefrontal cortex (mPFC) plays a key role in behavioral variability, action monitoring, and inhibitory control. The functional role of mPFC may change over the lifespan due to a number of aging-related issues, including dendritic regression, increased cAMP signaling, and reductions in the efficacy of neuromodulators to influence mPFC processing. A key neurotransmitter in mPFC is norepinephrine. Previous studies have reported aging-related changes in the sensitivity of mPFC-dependent tasks to noradrenergic agonist drugs, such as guanfacine. Here, we assessed the effects of yohimbine, an alpha-2 noradrenergic antagonist, in cohorts of younger and older rats in a classic test of spatial working memory (using a T-maze). Older rats (23–29 mo.) were impaired by a lower dose of yohimbine compared to younger animals (5–10 mo.). To determine if the drug acts on alpha-2 noradrenergic receptors in mPFC and if its effects are specific to memory-guided performance, we made infusions of yohimbine into mPFC of a cohort of young rats (6 mo.) using an operant delayed response task. The task involved testing rats in blocks of trials with memory- and stimulus-guided performance. Yohimbine selectively impaired memory-guided performance and was associated with error perseveration. Infusions of muscimol (a GABA-A agonist) at the same sites also selectively impaired memory-guided performance, but did not lead to error perseveration. Based on these results, we propose several potential interpretations for the role for the noradrenergic system in the performance of delayed response tasks, including the encoding of previous response locations, task rules (i.e., using a win-stay strategy instead of a win-shift strategy), and performance monitoring (e.g., prospective encoding of outcomes).