Projections from thalamic nucleus reuniens to medial septum enable extinction of remote fear memory

Aversive experiences lead to the formation of long-lasting memories. Despite the need to better understand how enduring fear memories can be attenuated, the underlying brain circuits remain largely unknown. In this study, employing a combination of genetic manipulations, neuronal circuit mapping, and chemogenetics in mice, we identify a new projection from the thalamic nucleus reuniens (RE) to the medial septum (MS), and show that this circuit is involved in the extinction of remote (30-day old), but not recent (1-day old), fear memories. These findings provide the first functional description of the RE[->]MS circuit and highlight the significance of the thalamo-septal regions in memory organization as a function of memory age, a phenomenon known as systems consolidation.