Contribution of specific serotonin receptors as well as hippocampal neurogenesis to pathological states such as depression and anxiety
Area of Research
Stem Cell Biology, Neurobiology of Learning & Memory, Animal Models of Psychiatric Disorders, Neurogenetics
Contribution of specific serotonin receptors as well as hippocampal neurogenesis to pathological states such as depression and anxiety.
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.
- Sahay A, Wilson DA, Hen R. (2011). Pattern separation: a common function for new neurons in hippocampus and olfactory bulb. Neuron;70(4):582-8. Review.
- Sahay A, Scobie KN, Hill AS, O'Carroll CM, Kheirbek MA, Burghardt NS, Fenton AA, Dranovsky A, Hen R. (2011). Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature; 472(7344):466-70.
- David, D., Samuels, B., Rainer, Q., Wang, J., Marsteller, D., Mendez, I., Drew, M., Craig, D., Guiard, B., Guilloux, J-P., Artymyshyn, R., Gardier, A., Gerald, C., Antonijevic, I., Leonardo, E., Hen, R. (2009) Behavioral effects of fluoxetine in an animal model of anxiety/depression are mediated by both neurogenesis-dependent and independent mechanisms. Neuron, 62, 1-15.
- Saxe MD, Malleret G, Vronskaya S, Mendez I, Garcia AD, Sofroniew MV, Kandel ER, Hen R. (2007). Paradoxical influence of hippocampal neurogenesis on working memory. Proc Natl Acad Sci U S A. 104(11): 4642-6.
- Dranovsky A, Hen R. (2006). Hippocampal neurogenesis: regulation by stress and antidepressants. Biol Psychiatry. 59(12): 1136-43. Review. Gross C, Hen R. (2004). The developmental origins of anxiety. Nat Rev Neurosci. 5(7):545-52. Review.
- Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 301(5634): 805-9.
- Gross C, Zhuang X, Stark K, Ramboz S, Oosting R, Kirby L, Santarelli L, Beck S, Hen R. (2002). Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature. 416(6879): 396-400.