Fang Wei, Chen Xi, He Jufang
Department of Neuroscience, City University of Hong Kong, Kowloon, Hong Kong.
Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong.
Neurobiol Stress. 2024 Oct 16;33:100680. doi: 10.1016/j.ynstr.2024.100680. eCollection 2024 Nov.
The basolateral amygdala (BLA) hyperactivity has been implicated in the pathophysiology of anxiety disorders. We recently found that enhancing inhibitory transmission in BLA by chemo-genetic activation of local interneurons (INs) can reduce stress-induced anxiety-like behaviors in mice. Cholecystokinin interneurons (CCK-INs) are a major part of INs in BLA. It remains unknown whether CCK-INs modulated inhibition in BLA can mediate anxiety. In the present study, we found that BLA CCK-INs project extensively to most local excitatory neurons. Activating these CCK-INs using chemo-genetics and optogenetics can both effectively suppress electrical-induced neuronal activity within the BLA. Additionally, we observed that direct and sustained activation of CCK-INs within the BLA via chemo-genetics can mitigate stress-induced anxiety-like behaviors in mice and reduce stress-induced hyperactivity within the BLA itself. Furthermore, augmenting inhibitory plasticity within the BLA through a brief, 10-min high-frequency laser stimulation (HFLS) of CCK-INs also reduce stress-induced anxiety-like behaviors in mice. Collectively, these findings underscore the pivotal role of BLA CCK-IN-mediated inhibitory transmission and plasticity in modulating anxiety.
基底外侧杏仁核（BLA）的活动亢进与焦虑症的病理生理学有关。我们最近发现，通过化学遗传学激活局部中间神经元（INs）来增强BLA中的抑制性传递，可以减少小鼠应激诱导的焦虑样行为。胆囊收缩素中间神经元（CCK-INs）是BLA中INs的主要组成部分。CCK-INs调节BLA中的抑制作用是否能介导焦虑尚不清楚。在本研究中，我们发现BLA中的CCK-INs广泛投射到大多数局部兴奋性神经元。使用化学遗传学和光遗传学激活这些CCK-INs都能有效抑制BLA内电诱导的神经元活动。此外，我们观察到，通过化学遗传学直接和持续激活BLA内的CCK-INs可以减轻小鼠应激诱导的焦虑样行为，并减少应激诱导的BLA自身的活动亢进。此外，通过对CCK-INs进行10分钟的短暂高频激光刺激（HFLS）来增强BLA内的抑制性可塑性，也能减少小鼠应激诱导的焦虑样行为。总的来说，这些发现强调了BLA中CCK-IN介导的抑制性传递和可塑性在调节焦虑中的关键作用。
