Expression of brain-derived neurotrophic factor in basolateral amygdala inputs to lateral septum is necessary for mice to identify socially novel individuals

Abstract

ABSTRACTBACKGROUNDThe lateral septum (LS) is activated by social novelty, and perturbing LS activity impairs social recognition. 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 social behavior is influenced by brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB. However, whether BDNF-TrkB signaling mediates social behavior by affecting function in LS circuits is not known.METHODSWe used single-molecule fluorescent in-situ hybridization to quantify expression of Ntrk2 (gene encoding TrkB) in LS. Viral transgenesis was used to induce cre-recombinase mediated TrkB knockdown in LS as well as for ablation and BDNF-depletion in neurons projecting from the basolateral amygdala (BLA) to the LS. We evaluated social recognition behavior using the three-chamber social interaction test, and assessed social novelty-induced c-Fos expression using fluorescence immunohistochemistry.RESULTSThe majority of GABAergic neurons in LS express TrkB. TrkB knockdown in LS abolishes social novelty recognition, and decreases LS activation in response to social novelty. Ablating BLA-LS projection neurons abolishes social novelty recognition behavior, an effect that is phenocopied by selectively depleting BDNF in this circuit.CONCLUSIONSSocial novelty recognition in the mouse requires both BDNF expression in BLA-LS projections neurons and intact TrkB signaling in the LS. These data support the hypothesis that BLA-LS projection neurons are a critical source of BDNF for activating LS TrkB signaling to control social novelty recognition.