A team of scientists led by Dr. Guan Ji-Song at the School of Life Science and Technology at ShanghaiTech has decoded the role of retrosplenial cortex in contextual fear conditioning, retrieval and extinction with in vivo two-photon imaging and TRAP. They discovered the extinction memory engrams in retrosplenial cortex and artificially controlled the level of fear by manipulating different memory engrams. Their work entitled ‘Switching from fear to no fear by different neural ensembles in mouse retrosplenial cortex’ was published online in Cerebral Cortex on March 19, 2019.
It has been reported that more than 70% of adults worldwide experience one or more traumatic events, such as violence, injury or death, in their lives, which can cause a variety of mental disorders, including posttraumatic stress disorder (PTSD). As a major clinical problem, PTSD is the most prevalent psychopathological disorder (Shalev A et al. 2017), the lifetime prevalence of which varies from 1.3% to 12.2% in different areas. Thus far, trauma-based exposure therapies have been thought to be the best-supported psychological intervention for PTSD, and these therapies involve a process similar to fear extinction training. To improve the therapeutic strategies for human PTSD and other related anxiety disorders, the neuronal mechanism underlying memory extinction must be revealed.
Here, by tracking immediate early gene (IEG) expression in vivo, we found that contextual fear extinction training evoked distinct neural ensembles in mouse retrosplenial cortex (RSC). The optogenetic reactivation of these extinction-activated neurons in the RSC was sufficient to suppress a fear response, while the reactivation of conditioning-activated neurons in the same area promoted a fear response. The generation of such an extinction-memory-related neural ensemble was associated with adult neurogenesis, as abolishing newborn neurons in the adult hippocampus via X-ray irradiation eliminated both the extinction-activated neurons in the RSC and the optogenetic-reactivation-induced suppression of contextual fear memory. Therefore, switching from fear to no fear in response to the same context is modulated by the RSC through an extinction-activated neural ensemble, the generation of which might require adult neurogenesis in the hippocampus.
Dr. Guan Ji-Song is the corresponding author. This work was supported by grants from the National Natural Science Foundation of China.
in vivo two-photon imaging (left) and the model for memory extinction in the RSC (Right)