A novel small molecule fluorescent agent called SERTlight specifically labels serotonin neurons in the mammalian brain. SERTlight is a substrate for the serotonin transporter (SERT) and accumulates inside serotonin neurons, producing a bright and selective optical signal. Unlike many other agents, SERTlight does not activate serotonin receptors or other common targets and is not released by neuronal activity or drugs like MDMA. It is compatible with other imaging tools and can label distant axonal projections while allowing simultaneous measurement of serotonin release. This new tool enables detailed study of the serotonin system in health and disease.
Classic psychedelics are thought to work by inducing neuroplasticity, often measured as dendritic arbor growth. This study tested whether psychedelics directly activate the TrkB receptor or BDNF/TrkB signaling, and whether they cause morphological growth in primary cortical neurons. Using a multimodal screening platform, the authors found that psychedelics do not directly modulate TrkB or BDNF-TrkB signaling, and that 5-HT2A receptor expression and functional levels are low. Psychedelics did not induce dendritogenesis, unlike BDNF which did. These results challenge previous findings and highlight the need for rigorous methods in studying neuroplasticity.