The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Cognitive Neuroscience, Radboudumc Nijmegen, Nijmegen, The Netherlands.
Nature. 2018 Nov;563(7731):397-401. doi: 10.1038/s41586-018-0682-1. Epub 2018 Nov 7.
Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions; however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons, where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here we demonstrate that dopamine increases the signal-to-noise ratio of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal grey (dPAG). Using an electrochemical approach, we reveal the precise time course of pinch-evoked dopamine release in the mPFC, and show that mPFC dopamine biases behavioural responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behaviours. mPFC-dPAG neurons display robust shock-induced excitations, as visualized by single-cell, projection-defined microendoscopic calcium imaging. Finally, photostimulation of dopamine terminals in the mPFC reveals an increase in the signal-to-noise ratio in mPFC-dPAG responses to aversive stimuli. Together, these data highlight how dopamine in the mPFC can selectively route sensory information to specific downstream circuits, representing a potential circuit mechanism for valence processing.
多巴胺调节内侧前额叶皮层（mPFC）的活动，从而介导多种行为功能；然而，确切的电路计算仍然未知。多巴胺可能通过调节 mPFC 神经元亚群的信号噪声比来作为一种潜在的统一模型，其中传递感觉信息的神经活动（信号）相对于自发放电（噪声）被放大。在这里，我们证明多巴胺可以增加投射到背侧periaqueductal 灰色（dPAG）的 mPFC 神经元对厌恶刺激的反应的信号噪声比。使用电化学方法，我们揭示了 mPFC 中夹压诱发多巴胺释放的确切时程，并表明 mPFC 多巴胺偏向于对厌恶刺激的行为反应。mPFC-dPAG 神经元的激活足以驱动回避和防御行为。通过单细胞、投影定义的微内窥镜钙成像，可以观察到 mPFC-dPAG 神经元对电击诱导的强烈兴奋。最后，光刺激 mPFC 中的多巴胺末梢揭示了 mPFC-dPAG 对厌恶刺激的反应中信号噪声比的增加。总的来说，这些数据强调了 mPFC 中的多巴胺如何选择性地将感觉信息路由到特定的下游回路，这代表了一种用于处理效价的潜在电路机制。
