Hefei National Laboratory for Physical Sciences at the Microscale, Chinese Academy of Sciences Key Laboratory of Brain Function and Diseases, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China.
Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Commun Biol. 2022 Apr 6;5(1):322. doi: 10.1038/s42003-022-03260-9.
Corticotropin-releasing factor (CRF) neurons are one of the most densely distributed cell types in the central amygdala (CeA), and are involved in a wide range of behaviors including anxiety and learning. However, the fundamental input circuits and patterns of CeA-CRF neurons are still unclear. Here, we generate a monosynaptic-input map onto CeA-CRF neurons at single-cell resolution via a retrograde rabies-virus system. We find all inputs are located in 44 nested subregions that directly innervate CeA-CRF neurons; most of them are top-down convergent inputs expressing Ca/calmodulin-dependent protein kinase II, and are centralized in cortex, especially in the layer 4 of the somatosensory cortex, which may directly relay information from the thalamus. While the bottom-up divergent inputs have the highest proportion of glutamate decarboxylase expression. Finally, en passant structures of single input neuron are revealed by in-situ reconstruction in a modified 3D-reference atlas, represented by a Periaqueductal gray-Subparafascicular nucleus-Subthalamic nucleus-Globus pallidus-Caudoputamen-CeA pathway. Taken together, our findings provide morphological and connectivity properties of inputs onto CeA-CRF neurons, which may provide insights for future studies interrogating circuit mechanisms of CeA-CRF neurons in mediating various functions.
促肾上腺皮质释放因子（CRF）神经元是中枢杏仁核（CeA）中分布最密集的细胞类型之一，参与广泛的行为，包括焦虑和学习。然而，CeA-CRF 神经元的基本输入回路和模式仍不清楚。在这里，我们通过逆行狂犬病毒系统以单细胞分辨率生成了一个单突触输入图谱到 CeA-CRF 神经元。我们发现所有输入都位于 44 个嵌套的子区域中，这些子区域直接支配 CeA-CRF 神经元；其中大多数是表达钙/钙调蛋白依赖性蛋白激酶 II 的自上而下会聚输入，集中在皮层，特别是在体感皮层的第 4 层，这可能直接从丘脑传递信息。而自下而上的发散输入谷氨酸脱羧酶表达的比例最高。最后，通过在改良的 3D 参考图谱中的原位重建揭示了单个输入神经元的过路结构，代表了中脑导水管周围灰质-副束核-丘脑底核-苍白球-尾状核-杏仁核通路。总之，我们的研究结果提供了 CeA-CRF 神经元输入的形态和连接特性，这可能为未来研究提供线索，以研究 CeA-CRF 神经元在介导各种功能中的回路机制。
