Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Nat Neurosci. 2015 Nov;18(11):1606-16. doi: 10.1038/nn.4116. Epub 2015 Sep 21.

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

Author information

1
Department of Psychiatry, Columbia University Medical Center and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, New York, USA.
2
Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy.
3
Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.

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.

Comment in

PMID:
26389840
PMCID:
PMC4624493
DOI:
10.1038/nn.4116
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center