Liu Wei-Zhu, Wang Chun-Yan, Wang Yu, Cai Mei-Ting, Zhong Wei-Xiang, Liu Tian, Wang Zhi-Hao, Pan Han-Qing, Zhang Wen-Hua, Pan Bing-Xing
Department of Biological Science, School of Life Science, Nanchang University, Nanchang, 330031, China.
Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang, 330031, China.
Cell Biosci. 2023 May 18;13(1):90. doi: 10.1186/s13578-023-01050-2.
Chronic stress exposure increases the risk of mental health problems such as anxiety and depression. The medial prefrontal cortex (mPFC) is a hub for controlling stress responses through communicating with multiple limbic structures, including the basolateral amygdala (BLA) and nucleus accumbens (NAc). However, considering the complex topographical organization of the mPFC neurons in different subregions (dmPFC vs. vmPFC) and across multiple layers (Layer II/III vs. Layer V), the exact effects of chronic stress on these distinct mPFC output neurons remain largely unknown.
We first characterized the topographical organization of mPFC neurons projecting to BLA and NAc. Then, by using a typical mouse model of chronic restraint stress (CRS), we investigated the effects of chronic stress on the synaptic activity and intrinsic properties of the two mPFC neuronal populations. Our results showed that there was limited collateralization of the BLA- and NAc-projecting pyramidal neurons, regardless of the subregion or layer they were situated in. CRS significantly reduced the inhibitory synaptic transmission onto the BLA-projecting neurons in dmPFC layer V without any effect on the excitatory synaptic transmission, thus leading to a shift of the excitation-inhibition (E-I) balance toward excitation. However, CRS did not affect the E-I balance in NAc-projecting neurons in any subregions or layers of mPFC. Moreover, CRS also preferentially increased the intrinsic excitability of the BLA-projecting neurons in dmPFC layer V. By contrast, it even caused a decreasing tendency in the excitability of NAc-projecting neurons in vmPFC layer II/III.
Our findings indicate that chronic stress exposure preferentially modulates the activity of the mPFC-BLA circuit in a subregion (dmPFC) and laminar (layer V) -dependent manner.
长期暴露于慢性应激会增加患焦虑和抑郁等心理健康问题的风险。内侧前额叶皮质（mPFC）是通过与包括基底外侧杏仁核（BLA）和伏隔核（NAc）在内的多个边缘系统结构进行通信来控制应激反应的枢纽。然而，考虑到mPFC神经元在不同亚区域（背内侧前额叶皮质与腹内侧前额叶皮质）和多层（第II/III层与第V层）中的复杂拓扑组织，慢性应激对这些不同的mPFC输出神经元的确切影响仍然很大程度上未知。
我们首先描绘了投射到BLA和NAc的mPFC神经元的拓扑组织。然后，通过使用典型的慢性束缚应激（CRS）小鼠模型，我们研究了慢性应激对这两种mPFC神经元群体的突触活动和内在特性的影响。我们的结果表明，投射到BLA和NAc的锥体神经元的侧支化有限，无论它们位于哪个亚区域或层。CRS显著降低了背内侧前额叶皮质第V层中投射到BLA的神经元的抑制性突触传递，而对兴奋性突触传递没有任何影响，从而导致兴奋-抑制（E-I）平衡向兴奋方向转变。然而，CRS在mPFC的任何亚区域或层中均未影响投射到NAc的神经元的E-I平衡。此外，CRS还优先增加了背内侧前额叶皮质第V层中投射到BLA的神经元的内在兴奋性。相比之下，它甚至导致腹内侧前额叶皮质第II/III层中投射到NAc的神经元的兴奋性有下降趋势。
我们的研究结果表明，长期暴露于慢性应激会优先以亚区域（背内侧前额叶皮质）和层（第V层）依赖性方式调节mPFC-BLA回路的活动。
