Mechanisms of Dopamine-dependent Plasticity in Auditory Cortex

通过将电刺激多巴胺神经元和纯音刺激相结合，可以在听觉皮质中诱导一种形式的可塑性；在复合刺激的重复刺激下，纯音将表现为皮质面积的扩大。当纯音刺激与基底前脑胆碱能神经元的刺激相结合时，也会出现类似的可塑性。在这里，我们通过检测多巴胺对大脑皮质对声刺激反应的急性影响，来研究多巴胺如何诱导可塑性。使用电压敏感染料的光学成像，我们能够以毫秒的时间分辨率记录大脑皮层的听觉反应。通过检查大脑皮层的强直反应，我们可以同时识别初级和次级皮质。这样的检查还导致在听觉皮质中发现了几个新的区域。然而，将多巴胺或其激动剂应用于大脑皮层，并没有引起听觉反应的变化。全身应用L多巴也未引起明显的反应改变。因此，我们开始研究乙酰胆碱的作用。应用奥托莫林可抑制对声刺激的初始兴奋反应和随后的抑制反应。接下来，我们想知道多巴胺和乙酰胆碱之间是否存在相互作用。我们发现，多巴胺和乙酰胆碱的联合应用没有引起听觉反应的变化，这表明多巴胺完全抑制了乙酰胆碱的所有作用。这些结果表明，多巴胺通过与乙酰胆碱相互作用诱导皮质可塑性的一种新机制。

One form of plasticity in the auditory cortex can be induced by combining electrical stimulation of dopamine neurons with a pure tone stimulation ; the pure tone will be represented by an enlarged cortical area after repeated stimulation with the combined stimuli. Similar plasticity occurs when pure tone stimulation is combined with stimulation of cholinergic neurons in the basal forebrain. Here we asked how dopamine might induce the plasticity by examining the acute effect of dopamine on cortical response to acoustic stimulations. Using optical imaging with voltage sensitive dyes, we were able to record auditory response in the cortex with millisecond temporal resolution. Examining the tonotopic responses in the cortex allowed us identifying both the primary and the secondary cortices. Such examinations also led to the finding of several new fields in the auditory cortices. Application of dopamine or its agonists to the cortex, however, caused no change in the auditory response. Systemic application of L-DOPA also failed to induce a significant change in the response. We thus set out to study the effect of acetylcholine. Application of Oxotromorine suppressed both the initial excitatory response and the following inhibitory responses to acoustic stimulations. We wondered next if there is any interaction between dopamine and acetylcholine. We found that co-application of dopamine and acetylcholine induced no change in the auditory response, indicating that dopamine completely suppressed all effects of acetylcholine. These results suggest a novel mechanism for dopamine in inducing plasticity in the cortex by interacting with acetylcholine.