Institute of Neurobiology, University of Tübingen, Tübingen, Germany.
J Neurosci. 2013 Aug 21;33(34):13724-34. doi: 10.1523/JNEUROSCI.0210-13.2013.
The lateral prefrontal cortex (PFC), a hub of higher-level cognitive processing, is strongly modulated by midbrain dopamine (DA) neurons. The cellular mechanisms have been comprehensively studied in the context of short-term memory, but little is known about how DA regulates sensory inputs to PFC that precede and give rise to such memory activity. By preparing recipient cortical circuits for incoming signals, DA could be a powerful determinant of downstream cognitive processing. Here, we tested the hypothesis that prefrontal DA regulates the representation of sensory signals that are required for perceptual decisions. In rhesus monkeys trained to report the presence or absence of visual stimuli at varying levels of contrast, we simultaneously recorded extracellular single-unit activity and applied DA to the immediate vicinity of the neurons by micro-iontophoresis. We found that DA modulation of prefrontal neurons is not uniform but tailored to specialized neuronal classes. In one population of neurons, DA suppressed activity with high temporal precision but preserved signal/noise ratio. Neurons in this group had short visual response latencies and comprised all recorded narrow-spiking, putative interneurons. In a distinct population, DA increased excitability and enhanced signal/noise ratio by reducing response variability. These neurons had longer visual response latencies and were composed exclusively of broad-spiking, putative pyramidal neurons. By gating sensory inputs to PFC and subsequently strengthening the representation of sensory signals, DA might play an important role in shaping how the PFC initiates appropriate behavior in response to changes in the sensory environment.
外侧前额叶皮层（PFC）是高级认知处理的中枢，强烈受到中脑多巴胺（DA）神经元的调节。在短期记忆的背景下，已经对其细胞机制进行了全面研究，但对于 DA 如何调节 PFC 之前的感觉输入以及导致这种记忆活动的机制知之甚少。通过为传入信号准备接收皮质回路，DA 可能成为下游认知处理的有力决定因素。在这里，我们测试了这样一个假设，即前额叶 DA 调节了用于知觉决策的感觉信号的表示。在经过训练以报告视觉刺激存在或不存在的恒河猴中，我们同时记录了细胞外单个单元的活动，并通过微电泳将 DA 施加到神经元的紧邻部位。我们发现，DA 对 PFC 神经元的调制不是均匀的，而是针对专门的神经元类型进行了调整。在一组神经元中，DA 以高精度抑制活动，但保持了信号/噪声比。该组中的神经元具有较短的视觉反应潜伏期，并且包括所有记录的窄峰，假定的中间神经元。在另一个不同的群体中，DA 通过减少反应变异性来增加兴奋性并提高信号/噪声比。这些神经元具有较长的视觉反应潜伏期，并且仅由宽峰，假定的锥体神经元组成。通过对 PFC 的感觉输入进行门控，然后增强感觉信号的表示，DA 可能在塑造 PFC 如何响应感觉环境的变化而启动适当的行为方面发挥重要作用。
