Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People's Republic of China.
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3799-3804. doi: 10.1073/pnas.1814292116. Epub 2019 Feb 11.
Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world's population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLA) project onto both medial prefrontal cortex glutamate (mPFC) and GABA (mPFC) neurons that locally innervate mPFC neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLA inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA-mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLA→mPFC circuit that controls the checking symptoms of OCD.
强迫症（OCD）影响全球人口的 1%至 3%。然而，强迫症过度检查症状的神经机制尚不完全清楚。我们使用病毒神经元示踪技术在小鼠中发现，来自杏仁基底外侧核（BLA）的谷氨酸能神经元投射到内侧前额叶皮质谷氨酸（mPFC）和 GABA（mPFC）神经元，这些神经元局部支配 mPFC 神经元。接下来，我们开发了一种 OCD 检查小鼠模型，使用喹吡罗诱导重复性检查行为。该模型表现出由增强的 BLA 输入调节的谷氨酸能 mPFC 微电路活性降低。这种适应性不良电路的光或化学遗传操作恢复了行为反应。在一项小鼠功能磁共振成像（fMRI）研究中验证了这些发现，其中 OCD 小鼠的 BLA-mPFC 功能连接性增加。总之，这些发现定义了一个独特的 BLA→mPFC 回路，该回路控制 OCD 的检查症状。
