Serotonin Signaling through Prefrontal Cortex 5-HT1A Receptors during Adolescence Can Determine Baseline Mood-Related Behaviors

Publication date: 31 January 2017
Source:Cell Reports, Volume 18, Issue 5
Author(s): Alvaro L. Garcia-Garcia, Qingyuan Meng, Sarah Canetta, Alain M. Gardier, Bruno P. Guiard, Christoph Kellendonk, Alex Dranovsky, E. David Leonardo
Lifelong homeostatic setpoints for mood-related behaviors emerge during adolescence. Serotonin (5-HT) plays an important role in refining the formation of brain circuits during sensitive developmental periods. In rodents, the role of 5-HT1A receptors in general and autoreceptors in particular has been characterized in anxiety. However, less is known about the role of 5-HT1A receptors in depression-related behavior. Here, we show that whole-life suppression of heteroreceptor expression results in a broad depression-like behavioral phenotype accompanied by physiological and cellular changes within medial prefrontal cortex-dorsal raphe proper (mPFC-DRN) circuitry. These changes include increased basal 5-HT in a mPFC that is hyporesponsive to stress and decreased basal 5-HT levels and firing rates in a DRN hyperactivated by the same stressor. Remarkably, loss of heteroreceptors in the PFC at adolescence is sufficient to recapitulate this depression-like behavioral syndrome. Our results suggest that targeting mPFC 5-HT1A heteroreceptors during adolescence in humans may have lifelong ramifications for depression and its treatment.

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Teaser

Garcia-Garcia et al. use transgenic and viral approaches to demonstrate that signaling through 5-HT1A heteroreceptors in the medial prefrontal cortex during adolescence is critical in establishing baseline mood setpoints.


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