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Role of molecularly defined lateral septum cell types and circuits in social behaviors

Neuropsychopharmacology (2025)Cite this article

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Impaired social functioning is a defining characteristic across all neuropsychiatric and neurodevelopmental disorders. Social behavior encompasses a broad range of interactions that may differ by sex, and accurately identifying the appropriate behavioral response to varied social stimuli is required for an animal’s ability to survive and reproduce. Early research implicated many brain regions in social behaviors, including the lateral septum (LS), prefrontal cortex (PFC), hippocampus, amygdala, and hypothalamus. However, only recently have we begun to understand how connections between these regions control social behaviors. Understanding the cell types and circuits involved in social behaviors is essential for understanding the etiology of impaired social functioning in brain disorders.

The LS, a GABAergic basal forebrain structure, sends and receives projections from all brain regions implicated in the control of social behavior, including the basolateral amygdala (BLA) and PFC. The LS receives direct input from brain derived neurotrophic factor (BDNF) expressing neurons in the BLA [1]. BLABDNF-LS neurons are essential for social novelty recognition, the ability to distinguish between novel and familiar conspecifics, as neuronal ablation or circuit-specific BDNF knockout blocks this behavior [1]. Conversely, LS-projecting corticotropin releasing hormone (CRH)-expressing neurons in the PFC are essential for familiarization [2], the ability to recognize a conspecific from previous interactions [2].

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References

  1. Rodriguez LA, Kim S-H, Page SC, Nguyen CV, Pattie EA, Hallock HL, et al. The basolateral amygdala to lateral septum circuit is critical for regulating social novelty in mice. Neuropsychopharmacology. 2023;48:529–39.

    Article  CAS  PubMed  Google Scholar 

  2. de León Reyes NS, Sierra Díaz P, Nogueira R, Ruiz -Pino A, Nomura Y, de Solis CA, et al. Corticotropin-releasing hormone signaling from prefrontal cortex to lateral septum suppresses interaction with familiar mice. Cell. 2023;186:4152–71.e31.

    Article  PubMed  Google Scholar 

  3. Simon RC, Loveless MC, Yee JX, Goh B, Cho SG, Nasir Z, et al. Opto-seq reveals input-specific immediate-early gene induction in ventral tegmental area cell types. Neuron. 2024;112:2721–31.e5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chen G, Lai S, Jiang S, Li F, Sun K, Wu X, et al. Cellular and circuit architecture of the lateral septum for reward processing. Neuron. 2024;112:2783–98.e9.

    Article  CAS  PubMed  Google Scholar 

  5. Li L, Durand-de Cuttoli R, Aubry AV, Burnett CJ, Cathomas F, Parise LF, et al. Social trauma engages lateral septum circuitry to occlude social reward. Nature. 2023;613:696–703.

    Article  CAS  PubMed  Google Scholar 

  6. Phillips RA, Oh S, Bach SV, Du Y, Miller RA, Kleinman JE, et al. Transcriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species. IScience. 2025;28:111820.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Keri Martinowich and Kristen Maynard for comments on the manuscript.

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  1. Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA

    Robert A. Phillips III & Stephanie C. Page

  2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Stephanie C. Page

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  1. Robert A. Phillips III
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  2. Stephanie C. Page
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RAPIII and SCP wrote the article.

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Correspondence to Stephanie C. Page.

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Phillips, R.A., Page, S.C. Role of molecularly defined lateral septum cell types and circuits in social behaviors. Neuropsychopharmacol. (2025). https://doi.org/10.1038/s41386-025-02216-x

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  • DOI: https://doi.org/10.1038/s41386-025-02216-x

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