Dr. Rene Hen is a Professor of Neuroscience and Pharmacology at Columbia University and the Director of the Division of Integrative Neuroscience in the Department of Psychiatry at the New York State Psychiatric Institute (NYSPI). He has been studying the mechanism of action of antidepressant medications as well as hippocampal neurogenesis for the past 25 years and has a strong background in molecular biology, pharmacology, gene targeting technologies and in behavioral studies. He is also the Director of the NYSTEM Cellular Imaging Facility. Dr. Hen and his lab have acquired the expertise to analyze large datasets including various gene expression and calcium imaging platforms, and they are actively collaborating with the Department of Computational Neuroscience at Columbia University.

Dr. Hen has been the director of a T32 training grant for the past 12 years and has mentored numerous students, postdoctoral fellows, and residents who went on to successful research careers both in academia and in industry. Dr. Hen’s goal is to foster a generation of researchers who are equally comfortable with basic science and clinical questions and who will provide us in the future with a better understanding of the mechanisms underlying neurological and psychiatric disorders. Dr. Hen is the Leader of the Conte Center for Suicide Prevention Project 2, “Animal Models of Suicide: Behavior, Neurobiological and Molecular Phenotypes”.

Research Focus

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 drugs with high specificity, as a number of the 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 Hen’s lab also has 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.

Select Publications

1. 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. PMID: 12907793.

2. Kheirbek MA, Klemenhagen KC, Sahay A, Hen R. (2012). Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders. Nat Neurosci. 15(12):1613-20. PMID: 2318769

3. Hill AS, Sahay A, Hen R. (2015). Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology PMID: 25833129

4. Jimenez JC, Su K, Goldberg AR, Luna VM, Biane JS, Ordek G, Zhou P, Ong SK, Wright MA, Zweifel L, Paninski L, Hen R, Kheirbek MA. (2018) Anxiety Cells in a Hippocampal-Hypothalamic Circuit. Neuron. 97(3):670-683.e6. PMID: 29397273.

5. Anacker C., Luna V., Stevens G., Millette A., Shores R., Jimenez JC., Chen B., Hen R (2018); Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus; Nature, 559, 98-102.

6. 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. PMCID: PMC3084370.

7. Kheirbek, MA, Drew, L, Burghardt NS, Costantini DO, Tannenholz L, Ahmari SE, Zeng H, Fenton AA, Hen R. (2013) Differential control of learning and anxiety along the dorso-ventral axis of the dentate Neuron. 6;77(5):955-68. PMCID: PMC3595120.

8. Denny CA, Kheirbek MA, Alba EL, Tanaka KF, Brachman RA, Laughman KB, Tomm NK, Turi GF, Losonczy A, and Hen R. (2014). Hippocampal Memory Traces Are Differentially Modulated By Experience, Time, And Adult Neurogenesis. Neuron. 83:189-201.

9. Stefanini F., Kheirbek M., Kushnir L., Jennings J., Deisseroth K., Stuber G., Hen R., Fusi S. A distributed neural code in ensembles of dentate gyrus granule cells. bioRxiv 292953; doi: https://doi.org/10.1101/292953.

10. Gross, C., Zhuang, X., Stark, K., Ramboz, S., Oosting, R., Kirby, L., Santarelli, L., Beck, S., and Hen, R. (2002). Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 416, 396-400.

11. Richardson-Jones JW, Craige CP, Guiard BP, Stephen A, Metzger KL, Kung HF, Gardier AM, Dranovsky A, David DJ, Beck SG, Hen R, Leonardo ED. (2010). 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron. 65(1):40-52.

12. Samuels BA, Anacker C, Hu A, Levinstein MR, Pickenhagen A, Tsetsenis T, Madroñal N, Donaldson ZR, Drew LJ, Dranovsky A, Gross CT, Tanaka KF, Hen R. (2015). 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response. Nat Neurosci. 18(11): 1606-16.

13. Nautiyal KM, Tanaka KF, Barr MM, Tritschler L, Le Dantec Y, David DJ, Gardier AM, Blanco C, Hen R, Ahmari SE. Distinct Circuits Underlie the Effects of 5-HT1B Receptors on Aggression and Impulsivity. Neuron. 2015 May 6;86(3):813-26.