MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, 199 Chang'an South Road, Xi'an, 710062, China; Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, 555 Qiangye Road, Shanghai, 201210, China.
MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, 199 Chang'an South Road, Xi'an, 710062, China.
Biochem Biophys Res Commun. 2024 Aug 6;720:150073. doi: 10.1016/j.bbrc.2024.150073. Epub 2024 May 8.
Astrocytes in the central nervous system play a vital role in modulating synaptic transmission and neuronal activation by releasing gliotransmitters. The 5-HTergic neurons in the ventrolateral periaqueductal gray (vlPAG) are important in anxiety processing. However, it remains uncertain whether the regulation of astrocytic activity on vlPAG 5-HTergic neurons is involved in anxiety processing. Here, through chemogenetic manipulation, we explored the impact of astrocytic activity in the PAG on the regulation of anxiety. To determine the role of astrocytes in the control of anxiety, we induced anxiety-like behaviors in mice through foot shock and investigated their effects on synaptic transmission and neuronal excitability in vlPAG 5-HTergic neurons. Foot shock caused anxiety-like behaviors, which were accompanied with the increase of the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs), the area of slow inward currents (SICs), and the spike frequency of action potentials (AP) in vlPAG 5-HTergic neurons. The chemogenetic inhibition of vlPAG astrocytes was found to attenuate stress-induced anxiety-like behaviors and decrease the heightened synaptic transmission and neuronal excitability of vlPAG 5-HTergic neurons. Conversely, chemogenetic activation of vlPAG astrocytes triggered anxiety-like behaviors, enhanced synaptic transmission, and increased the excitability of vlPAG 5-HTergic neurons in unstressed mice. In summary, this study has provided initial insights into the pathway by which astrocytes influence behavior through the rapid regulation of associated neurons. This offers a new perspective for the investigation of the biological mechanisms underlying anxiety.
中枢神经系统中的星形胶质细胞通过释放神经胶质递质在调节突触传递和神经元激活方面起着至关重要的作用。腹外侧导水管周围灰质（vlPAG）中的 5-HT 能神经元在焦虑处理中很重要。然而，星形胶质细胞活性对 vlPAG 5-HT 能神经元的调节是否参与焦虑处理仍不确定。在这里，我们通过化学遗传操作探讨了 PAG 中星形胶质细胞活性对焦虑调节的影响。为了确定星形胶质细胞在控制焦虑中的作用，我们通过足底电击诱导小鼠出现焦虑样行为，并研究它们对 vlPAG 5-HT 能神经元突触传递和神经元兴奋性的影响。足底电击引起焦虑样行为，伴随着 vlPAG 5-HT 能神经元中兴奋性突触后电流（mEPSC）幅度和频率、缓慢内向电流（SIC）面积和动作电位（AP）频率的增加。发现 vlPAG 星形胶质细胞的化学遗传抑制可减轻应激引起的焦虑样行为，并降低 vlPAG 5-HT 能神经元中增强的突触传递和神经元兴奋性。相反，vlPAG 星形胶质细胞的化学遗传激活会引发焦虑样行为，增强未受应激小鼠中 vlPAG 5-HT 能神经元的突触传递，并增加其兴奋性。总之，这项研究为星形胶质细胞通过快速调节相关神经元影响行为的途径提供了初步的见解。这为研究焦虑的生物学机制提供了一个新的视角。
