Ramesh Kritika, Nair Indrajith R, Yamamoto Naoki, Ogawa Sachie K, Terranova Joseph I, Kitamura Takashi
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Biology, Kyushu University, Fukuoka, JPN, Japan.
Mol Brain. 2025 Feb 25;18(1):14. doi: 10.1186/s13041-025-01188-9.
Observational fear (OF) is the ability to vicariously experience and learn from another's fearful situation, enabling adaptive responses crucial for survival. It has been shown that the anterior cingulate cortex (ACC) and basolateral amygdala (BLA) are crucial for OF. A subset of neurons in the ACC is activated when observing aversive events in the demonstrator, which elicits OF. However, the neural circuit mechanisms underlying the expression of OF-related activity in the ACC remain unexplored. Previous studies have shown that the mediodorsal thalamus (MD) is crucial for OF, and MD neurons project to the ACC. Therefore, we hypothesize that the projection from MD to ACC may facilitate the OF-related activity in the ACC. By utilizing in vivo calcium imaging combined with the optogenetic terminal inhibition of MD-ACC pathway, we found that a subset of ACC neurons was activated when observing demonstrator's fearful situation in male mice. Furthermore, the optogenetic inhibition of the MD-ACC projection during the demonstrator's aversive moments significantly suppressed the OF-related activity in the ACC. Our data suggests that the MD-ACC projection plays a role in OF-related activity in ACC neurons.
观察性恐惧（OF）是一种能够通过间接体验并从他人的恐惧情境中学习的能力，它能引发对生存至关重要的适应性反应。研究表明，前扣带回皮层（ACC）和基底外侧杏仁核（BLA）对观察性恐惧至关重要。当观察示范者的厌恶事件时，ACC中的一部分神经元会被激活，从而引发观察性恐惧。然而，ACC中与观察性恐惧相关活动表达的神经回路机制仍未得到探索。先前的研究表明，背内侧丘脑（MD）对观察性恐惧至关重要，且MD神经元投射至ACC。因此，我们推测从MD到ACC的投射可能会促进ACC中与观察性恐惧相关的活动。通过结合体内钙成像技术与对MD-ACC通路的光遗传学终末抑制，我们发现，在雄性小鼠观察示范者的恐惧情境时，ACC中的一部分神经元被激活。此外，在示范者出现厌恶时刻对MD-ACC投射进行光遗传学抑制，可显著抑制ACC中与观察性恐惧相关的活动。我们的数据表明，MD-ACC投射在ACC神经元与观察性恐惧相关的活动中发挥作用。
