PT  - JOURNAL ARTICLE
AU  - Lionel A. Rodriguez
AU  - Sun-Hong Kim
AU  - Stephanie C. Page
AU  - Claudia V. Nguyen
AU  - Elizabeth A. Pattie
AU  - Henry L. Hallock
AU  - Jessica Valerino
AU  - Kristen R. Maynard
AU  - Andrew E. Jaffe
AU  - Keri Martinowich
TI  - Expression of brain-derived neurotrophic factor in basolateral amygdala inputs to lateral septum is necessary for mice to identify socially novel individuals
AID  - 10.1101/2021.10.21.464669
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.21.464669
4099  - http://biorxiv.org/content/early/2021/10/22/2021.10.21.464669.short
4100  - http://biorxiv.org/content/early/2021/10/22/2021.10.21.464669.full
AB  - BACKGROUND The 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.METHODS We 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.RESULTS The 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.CONCLUSIONS Social 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.Competing Interest StatementThis work was supported by internal funding from the Lieber Institute for Brain Development, and the National Institute of Mental Health (R01MH105592 to KM). Andrew E. Jaffe is now a full time employee at Neumora Therapeutics, a for-profit biotechnology company, which is unrelated to the contents of this manuscript. Sun-Hong Kim is now employed by Genentech. Their contributions to the manuscript were made while previously employed by the Lieber Institute for Brain Development. No other authors have financial relationships with commercial interests, and the authors declare no competing interests.