ABSTRACT The lateral septum (LS) is a GABAergic region in the basal forebrain that is implicated in sociability. However, the neural circuits and cell signaling pathways that converge on the LS to mediate social behaviors aren’t well understood. Multiple lines of evidence suggest that brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays important roles in social behavior. While BDNF is not locally produced in LS, we demonstrate that nearly all GABAergic neurons in LS express TrkB. Local knock-down of TrkB expression from LS neurons decreased sociability and reduced recruitment of social novelty-induced neural activity. Since BDNF is not synthesized in LS, we evaluated which inputs to the LS could serve as potential BDNF sources for controlling sociability. By selectively ablating inputs to LS, we demonstrated that inputs from the basolateral amygdala (BLA), but not ventral CA1 (vCA1), regulate sociability. Moreover, depleting BDNF selectively in BLA-LS projection neurons phenocopied the decreased sociability observed following either local LS TrkB knockdown or ablation of BLA-LS inputs. These data support the hypothesis that BLA-LS projection neurons could serve as a critical source of BDNF for activating TrkB signaling in LS neurons to control sociability.

The basolateral amygdala to lateral septum circuit is critical for regulating sociability in mice