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

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Bibliographic Details
Title:	5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response.
Authors:	Samuels, Benjamin Adam, Anacker, Christoph, Hu, Alice, Levinstein, Marjorie R, Pickenhagen, Anouchka, Tsetsenis, Theodore, Madroñal, Noelia, Donaldson, Zoe R, Drew, Liam John, Dranovsky, Alex, Gross, Cornelius T, Tanaka, Kenji F, Hen, René
Source:	Nature Neuroscience. Nov2015, Vol. 18 Issue 11, p1606-1616. 11p. 7 Graphs.
Subjects:	Serotonin uptake inhibitors, Dentate gyrus, Antidepressants, Developmental neurobiology, Serotonin
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. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
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. [ABSTRACT FROM AUTHOR]
ISSN:	10976256
DOI:	10.1038/nn.4116