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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
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.
Representative Recent Publications
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.
A, Scobie KN, Hill AS, O'Carroll CM, Kheirbek MA, Burghardt NS, Fenton
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):
- 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.
- 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):
- 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.