Cholinergic mediation of attention - Contributions of phasic and tonic increases in prefrontal cholinergic activity
Cholinergic mediation of attention - Contributions of phasic and tonic increases in prefrontal cholinergic activity
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DOI：
10.1196/annals.1417.021
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Sarter, Martin
中科院分区：
文献类型：
--
作者：
Parikh, Vinay;Sarter, Martin
与经典的乙酰胆碱（ACh）作为一种影响唤醒状态的缓慢作用的神经调节剂的描述相反，采用酶选择性微电极实时监测注意任务执行大鼠皮层ACh释放的实验结果表明，胆碱能信号在多个时间尺度上表现，（秒、数十秒和分钟）支持并且是所定义的认知操作的中介所必需的。具体来说，在前额叶皮层，第二个基础的胆碱能信号支持检测行为的重要线索。与这些前额叶胆碱能瞬变相反，在皮层的其他地方也观察到表现在较低的时间分辨率的性能相关的胆碱能活动。虽然紧张性胆碱能信号水平与提示诱发的胆碱能瞬变的幅度相关，后者与反应潜伏期相关，但多种胆碱能信号模式之间的相互关系和相互作用仍不清楚。假设传入电路有助于调节第二与分钟为基础的胆碱能信号进行了讨论。胆碱能瞬变及其在线索检测和注意力表现中的关键作用的发现形成了关于认知障碍中胆碱能功能障碍的性质的新假设的基础，并为神经精神和神经退行性疾病的认知症状的治疗的发展提供了新的靶点。
Contrary to the classic description of acetylcholine (ACh) as a slowly acting neuromodulator that influences arousal states, results from experiments that employed enzyme-selective microelectrodes for the real-time monitoring of ACh release in the cortex of attentional task-performing rats indicate that cholinergic signals manifesting on multiple timescales (seconds, tens of seconds, and minutes) support, and are necessary for, the mediation of defined cognitive operations. Specifically, in the prefrontal cortex, second-based cholinergic signals support the detection of behaviorally significant cues. In contrast to these prefrontal cholinergic transients, performance-associated cholinergic activity that manifested at lower temporal resolution also was observed elsewhere in the cortex. Although tonic cholinergic signal levels were correlated with the amplitudes of cue-evoked cholinergic transients, and the latter with response latencies, the interrelationships and interactions between the multiple cholinergic signaling modes remains unclear. Hypotheses concerning the afferent circuitry contributing to the regulation of second- versus minute-based cholinergic signals are discussed. The discovery of cholinergic transients and their crucial role in cue detection and attentional performance form the basis for new hypotheses about the nature of cholinergic dysfunction in cognitive disorders and offer new targets for the development of treatments for the cognitive symptoms of neuropsychiatric and neurodegenerative disorders.