Neurocentre Magendie, INSERM 1215, Université de Bordeaux, Bordeaux, France.
Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nat Commun. 2023 Aug 21;14(1):5073. doi: 10.1038/s41467-023-40517-1.
Responses of the insular cortex (IC) and amygdala to stimuli of positive and negative valence are altered in patients with anxiety disorders. However, neural coding of both anxiety and valence by IC neurons remains unknown. Using fiber photometry recordings in mice, we uncover a selective increase of activity in IC projection neurons of the anterior (aIC), but not posterior (pIC) section, when animals are exploring anxiogenic spaces, and this activity is proportional to the level of anxiety of mice. Neurons in aIC also respond to stimuli of positive and negative valence, and the strength of response to strong negative stimuli is proportional to mice levels of anxiety. Using ex vivo electrophysiology, we characterized the IC connection to the basolateral amygdala (BLA), and employed projection-specific optogenetics to reveal anxiogenic properties of aIC-BLA neurons. Finally, we identified that aIC-BLA neurons are activated in anxiogenic spaces, as well as in response to aversive stimuli, and that both activities are positively correlated. Altogether, we identified a common neurobiological substrate linking negative valence with anxiety-related information and behaviors, which provides a starting point to understand how alterations of these neural populations contribute to psychiatric disorders.
岛叶皮层（IC）和杏仁核对正性和负性效价刺激的反应在焦虑障碍患者中发生改变。然而，IC 神经元的焦虑和效价的神经编码仍然未知。使用小鼠光纤光度记录，当动物探索焦虑空间时，我们发现前（aIC）而不是后（pIC）部的 IC 投射神经元的活动选择性增加，并且这种活动与小鼠的焦虑水平成正比。aIC 中的神经元也对正性和负性效价的刺激做出反应，对强负性刺激的反应强度与小鼠的焦虑水平成正比。通过离体电生理学，我们描述了 IC 与基底外侧杏仁核（BLA）的连接，并采用投射特异性光遗传学来揭示 aIC-BLA 神经元的焦虑特性。最后，我们发现 aIC-BLA 神经元在焦虑空间中以及对厌恶刺激的反应中被激活，并且这两种活动呈正相关。总的来说，我们确定了一个将负效价与焦虑相关信息和行为联系起来的共同神经生物学基础，这为理解这些神经群体的改变如何导致精神障碍提供了一个起点。
