5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response

Benjamin Adam Samuels, Christoph Anacker, Alice Hu, Marjorie R. Levinstein, Anouchka Pickenhagen, Theodore Tsetsenis, Noelia Madroñal, Zoe R. Donaldson, Liam John Drew, Alex Dranovsky, Cornelius T. Gross, Kenji Tanaka, René Hen

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Adult hippocampal neurogenesis is necessary for some of the responses to SSRIs, but it is not known whether mature dentate gyrus granule cells (DG GCs) also contribute. We deleted the serotonin 1A receptor (5HT1AR, a receptor required for the SSRI response) specifically from DG GCs and found that the effects of the SSRI fluoxetine on behavior and the hypothalamic-pituitary-adrenal (HPA) axis were abolished. By contrast, mice lacking 5HT1ARs only in young adult-born GCs (abGCs) showed normal fluoxetine responses. Notably, 5HT1AR-deficient mice engineered to express functional 5HT1ARs only in DG GCs responded to fluoxetine, indicating that 5HT1ARs in DG GCs are sufficient to mediate an antidepressant response. Taken together, these data indicate that both mature DG GCs and young abGCs must be engaged for an antidepressant response.

Original languageEnglish
Pages (from-to)1606-1616
Number of pages11
JournalNature Neuroscience
Volume18
Issue number11
DOIs
Publication statusPublished - 2015 Nov 1

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of '5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response'. Together they form a unique fingerprint.

  • Cite this

    Samuels, B. A., Anacker, C., Hu, A., Levinstein, M. R., Pickenhagen, A., Tsetsenis, T., Madroñal, N., Donaldson, Z. R., Drew, L. J., Dranovsky, A., Gross, C. T., Tanaka, K., & Hen, R. (2015). 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response. Nature Neuroscience, 18(11), 1606-1616. https://doi.org/10.1038/nn.4116