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Publication : Distinct circuits in anterior cingulate cortex encode safety assessment and mediate flexibility of fear reactions.

First Author  Wu K Year  2023
Journal  Neuron Volume  111
Issue  22 Pages  3650-3667.e6
PubMed ID  37652003 Mgi Jnum  J:352805
Mgi Id  MGI:7550299 Doi  10.1016/j.neuron.2023.08.008
Citation  Wu K, et al. (2023) Distinct circuits in anterior cingulate cortex encode safety assessment and mediate flexibility of fear reactions. Neuron 111(22):3650-3667.e6
abstractText  Safety assessment and threat evaluation are crucial for animals to live and survive in the wilderness. However, neural circuits underlying safety assessment and their transformation to mediate flexibility of fear-induced defensive behaviors remain largely unknown. Here, we report that distinct neuronal populations in mouse anterior cingulate cortex (ACC) encode safety status by selectively responding under different contexts of auditory threats, with one preferably activated when an animal staysing in a self-deemed safe zone and another specifically activated in more dangerous environmental settings that led to escape behavior. The safety-responding neurons preferentially target the zona incerta (ZI), which suppresses the superior colliculus (SC) via its GABAergic projection, while the danger-responding neurons preferentially target and excite SC. These distinct corticofugal pathways antagonistically modulate SC responses to threat, resulting in context-dependent expression of fear reactions. Thus, ACC serves as a critical node to encode safety/danger assessment and mediate behavioral flexibility through differential top-down circuits.
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