Department Psychology & Neuroscience, University of Michigan, Ann Arbor, Michigan 48109
J Neurosci. 2020 Jan 22;40(4):712-719. doi: 10.1523/JNEUROSCI.1305-19.2019.
Conceptualizations of cholinergic signaling as primarily spatially diffuse and slow-acting are based largely on measures of extracellular brain ACh levels that require several minutes to generate a single data point. In addition, most such studies inhibited the highly potent catalytic enzyme for ACh, AChE, to facilitate measurement of ACh. Absent such inhibition, AChE limits the presence of ambient ACh and thus renders it unlikely that ACh influences target regions via slow changes in extracellular ACh concentrations. We describe an alternative view by which forebrain signaling in cortex driving cognition is largely phasic (milliseconds to perhaps seconds), and unlikely to be volume-transmitted. This alternative is supported by new evidence from real-time amperometric recordings of cholinergic signaling indicating a specific function of rapid, phasic, transient cholinergic signaling in attentional contexts. Previous neurochemical evidence may be reinterpreted in terms of integrated phasic cholinergic activity that mediates specific behavioral and cognitive operations; this reinterpretation fits well with recent computational models. Optogenetic studies support a causal relationship between cholinergic transients and behavior. This occurs in part via transient-evoked muscarinic receptor-mediated high-frequency oscillations in cortical regions. Such oscillations outlast cholinergic transients and thus link transient ACh signaling with more sustained postsynaptic activity patterns to support relatively persistent attentional biases. Reconceptualizing cholinergic function as spatially specific, phasic, and modulating specific cognitive operations is theoretically powerful and may lead to pharmacologic treatments more effective than those based on traditional views. Diverse Spatiotemporal Scales of Cholinergic Signaling in the Neocortex, by Anita A. Disney and Michael J. Higley.
概念化胆碱能信号主要是空间弥散和缓慢作用的，这主要基于需要几分钟才能生成一个数据点的脑外 ACh 水平的测量。此外，大多数此类研究抑制了 ACh 的高效催化酶 AChE，以方便 ACh 的测量。如果没有这种抑制，AChE 会限制环境 ACh 的存在，从而使 ACh 不太可能通过缓慢改变细胞外 ACh 浓度来影响靶区。我们描述了另一种观点，即大脑皮层的前脑信号驱动认知主要是相位性的（毫秒到秒），不太可能通过体积传递。这种替代观点得到了实时安培记录胆碱能信号的新证据的支持，该证据表明在注意力环境中，快速、相位性、短暂的胆碱能信号具有特定的功能。以前的神经化学证据可以根据快速、相位性、短暂的胆碱能信号在整合相位胆碱能活动中的特定功能进行重新解释，这种重新解释与最近的计算模型非常吻合。光遗传学研究支持胆碱能瞬变与行为之间的因果关系。这部分是通过皮质区域中短暂诱发的毒蕈碱受体介导的高频振荡来实现的。这种振荡持续时间超过胆碱能瞬变，从而将短暂的 ACh 信号与更持续的突触后活动模式联系起来，以支持相对持久的注意力偏向。将胆碱能功能重新概念化为空间特异性、相位性和调节特定认知操作在理论上具有强大的功能，并且可能导致比基于传统观点的药物治疗更有效。Anita A. Disney 和 Michael J. Higley 的《新皮层中的胆碱能信号的多种时空尺度》。
