Rene Hen
USERN Advisory Board
René Hen’s research is focused on the contribution of serotonin (5-HT) receptors to pathological states such as depression and anxiety. Pharmacological studies and molecular cloning have identified several subtypes of receptors with distinct properties, signaling systems, and tissue distributions. However, the study of the function of individual serotonin receptor subtypes has been hampered by the lack of specific drugs. In addition, a number of the serotonergic drugs that are active in the treatment of neuropsychiatric disorders influence the whole serotonergic system. For example, antidepressants such as fluoxetine are 5-HT uptake blockers and potentiate the action of 5-HT at multiple post-synaptic sites. To dissect the contributions of individual serotonin receptors to physiology and behavior, mouse mutants lacking individual receptor subtypes were created in his laboratory, providing genetic models for a number of human behavioral traits such as impulsiveness, depression, and anxiety. Tissue specific and conditional knockouts are currently being used to identify the neural circuits underlying these traits. Recently his lab has also been investigating the function of the ventral hippocampus and the contribution of hippocampal neurogenesis to mood and cognition. Specifically, they have shown that antidepressants stimulate the division of neuronal progenitor cells in the dentate gyrus, which in turn results in an increase in the number of immature neurons in the adult hippocampus. Furthermore, using various ablation strategies they have shown that hippocampal neurogenesis is required for some of the behavioral effects of antidepressants. Novel antidepressant therapies aimed at targeting directly hippocampal stem cells are currently under investigation.
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