Distinct Roles of Segregated Transmission of the Septo-Habenular Pathway in Anxiety and Fear

The posterior septum consisting of the triangular septum (TS) and the bed nucleus of the anterior commissure (BAG) is predominantly linked with the medial habenula (MHb) and has been implicated in the control of anxiety and fear responses. However, its anatomical and functional linkage has largely remained elusive. We established a transgenic mouse model in which the TS and BAG projection neurons were visualized by GFP fluorescence and selectively eliminated by immunotoxin-mediated cell targeting. The linkage between the TS/BAC and the MHb constitutes two parallel pathways composed of the TS-ventral MHb, the core part of the interpeduncular nucleus (IPN), and the BAG-dorsal MHb, the peripheral part of the IPN. Ablation of the TS and BAG projection neurons selectively impaired anxiety and enhanced fear responses and learning, respectively. Inputs from the TS and BAC to the MHb are thus segregated by two parallel pathways and play specialized roles in controlling emotional behaviors.