NEURAL REPRESENTATION OF AVERSIVE MEMORIES IN NUCLEUS REUNIENS DURING EXPRESSION AND EXTINCTION OF COMPLEX DEFENSIVE RESPONSES

Learning danger is fundamental for survival, but effective suppression of traumatic memories is essential to prevent development of pathological conditions. While previous studies have revealed neural circuits mediating attenuation of simplified aversive memories characterized by freezing, traumatic memory is clinically associated with a number of symptoms. Similarly, mice display a wide repertoire of defensive behaviors and effective extinction paradigms should have the potential to broadly attenuate them. Despite the high clinical relevance, how extinction promoting circuits regulate different defensive behaviors remains unknown.
To address this gap, we developed a novel behavioral paradigm using a three-compartment platform, which is designed to observe mixed, naturalistic defensive behaviors. In this paradigm, mice showed avoidance, stretch posture and flight behavior following aversive conditioning with electrical footshock. After repeated exposure to the conditioned platform, mice gradually extinguished the learned defensive responses. Using fiber photometry, we investigated neural representation of aversive and extinction memories in the nucleus reuniens of the thalamus (NRe), which is well connected with emotion-processing brain regions. We found that calcium response in NRe is modulated differently by distinct defensive behaviors, including stretch posture and flight. In addition, we observed that defensive behavior-locked NRe activities are weakened after extinction learning. These findings demonstrate that NRe neurons encode aversive and extinction memories which accompany with mixed behavioral responses, suggesting its potential to orchestrate adaptive control of diverse defensive behaviors.