title: 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response.
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.
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Benjamin Adam
authors.initials: BA
authors.lastname: Samuels
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Anacker
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Hu
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Marjorie R
authors.initials: MR
authors.lastname: Levinstein
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Anouchka
authors.initials: A
authors.lastname: Pickenhagen
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy.
authors.forename: Theodore
authors.initials: T
authors.lastname: Tsetsenis
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy.
authors.forename: Noelia
authors.initials: N
authors.lastname: Madroñal
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Zoe R
authors.initials: ZR
authors.lastname: Donaldson
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Liam John
authors.initials: LJ
authors.lastname: Drew
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Dranovsky
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy.
authors.forename: Cornelius T
authors.initials: CT
authors.lastname: Gross
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: René
authors.initials: R
authors.lastname: Hen
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects*; D018891:Dentate Gyrus / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A