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. We also demonstrate that the activity of this circuit, as well as consolidation of remote extinction memory, require autophosphorylation of αCaMKII, a key signaling molecule in the excitatory synapses. Our 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.