Techniques for in vivo serotonin detection in the brain: State of the art

Neuronal circuits in the brain that utilize the neurotransmitter serotonin are essential to the regulation of mood and emotional expression. Disruptions in serotonin signaling underlie neuropsychiatric conditions such as depression and anxiety. However, the cellular mechanisms that regulate serotonergic signaling in the brain in healthy and diseased states remain to be better understood. In particular, as more is learned about serotonin in the brain, we recognize an urgent need to develop techniques capable of mapping its complex spatiotemporal dynamics in awake, behaving animals. Notably, analytical methods to detect serotonin in situ, including tomography, are widely used but still recognized as limited in terms of their spatiotemporal resolution, their methodological caveats, and their technical limitations when cross-referenced with behavioral studies. To overcome such limitations, genetically encoded serotonin indicators were developed, leading to the introduction of novel imaging modalities that enable researchers to achieve remarkable spatiotemporal resolution in the study of serotonergic circuits in preclinical models of neuropsychiatric disorders. These novel approaches, while remarkably powerful, are also not without limitations. Here, we review the current techniques for detecting and quantifying serotonin in vivo within the brain and discuss how novel approaches such as genetically encoded serotonin indicators will lead to new insights into the roles of serotonergic circuits in health and disease.