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The incidence and complexity of mental illnesses and cognitive impairments associated with ageing and Alzheimer’s disease underscores the need to develop novel treatments. Our mission is to generate fundamental insights into the role of adult hippocampal neurogenesis, the process by which neural stem cells generate dentate granule neurons throughout life, in hippocampal functions in encoding, memory processing and modulation of mood. By integrating cellular, circuit, systems and behavioral interrogation of adult hippocampal neurogenesis, we aspire to rejuvenate and re-engineer hippocampal circuitry to optimize performance in diseases such as PTSD, Alzheimer’s disease and ageing.
To address this goal, we have established a multifaceted research program that integrates inducible mouse- and viral-genetics, pharmaco- and optogenetics, synaptic tracing, in vivo awake behaving optical imaging, 2 photon imaging, human cellular reprogramming, and behavioral analysis. Specifically, we are interested in the following questions.
1. How are neural stem cell activation-quiescence decisions physiologically regulated?
2. What are the mechanisms underlying lineage homeostasis and experience dependent integration of adult-born neurons?
3. How do properties and connectivity of adult-born neurons causally relate to their encoding and memory functions?
4. How does adult hippocampal neurogenesis influence hippocampal activity and limbic circuits sub serving mood?
5. How do our studies on properties and connectivity of hippocampal neurons in rodents inform our thinking of human hippocampal neuronal subtypes in health and disease?
6. What are the molecular mechanisms operational in the hippocampus underlying resilience and vulnerability to stress?
Duong "Izzy" Chu, BA in Neuroscience and Behavior (Vassar College)
Nannan Guo, Ph.D. (Fudan University)
Kathleen McAvoy, Ph.D. (University of Rochester)
Antoine Besnard, Ph.D. (INSERM/CNRS/UPMC, Paris)
Tara Raam (Program in Neuroscience)
Hugo Vega-Ramirez (Program in Neuroscience)
Alexia Zagouras (Harvard)
Christine Xu (Harvard)
We are always looking for highly motivated individuals to contribute to science in the lab and join our community. Potential candidates must be highly self-motivated and enthusiastic about taking on new challenges. Projects will involve a combination of molecular genetic and viral based manipulations of neural circuits and stem cells in mice, optical imaging, optogenetics and behavioral assays. Postdoctoral candidates should have demonstrated research productivity, independent thinking and rigorous training in molecular, behavioral, developmental or systems neuroscience. Candidates with a strong background in other fields (eg. molecular biology, neuropharmacology) are also welcome to apply. Interested candidates should send their resume/CV and 3 letters of reference to Dr. Amar Sahay (email@example.com).
Antoine Besnard and Amar Sahay. Adult hippocampal neurogenesis, fear generalization and stress. Impact of Stress on the Brain: Pathology, Treatment and Prevention 2016 Neuropsychopharmacology Reviews: The Next Generation of Progress Volume IX, Editors: Kerry Ressler and Jordan Smoller (Jun 12. doi: 10.1038/npp.2015.167.)
Alik Widge and Amar Sahay. Closing the Loop in Deep Brain Stimulation for psychiatric disorders: Lessons from Motor Neural Prosthetics. 2016 Neuropsychopharmacology Reviews (Accepted).
Kathleen McAvoy, Antoine Besnard and Amar Sahay. Adult hippocampal neurogenesis and pattern separation in DG: A role for feedback inhibition in modulating sparseness to govern population-based coding. Frontiers in Systems Neuroscience (2015) 9:120. PMC4542503.
Kathleen McAvoy, Craig Russo, Shannen Kim, Genelle Rankin, and Amar Sahay. Fluoxetine induces input-specific dendritic spine remodeling in adulthood and middle age. Hippocampus April 7, 2015 doi: 10.1002/hipo.22464
Alexis Hill, Amar Sahay* and Rene Hen*. Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology. 2015 Apr 2. 40(10):2368-78 PMC4538351. * Co-corresponding author.
Taruna Ikrar, Nannan Guo, Kaiwen He, Antoine Besnard, Sally Levinson, Alexis Hill, Hey-Kyoung Lee, Rene Hen, Xiangmin Xu and Amar Sahay. Adult neurogenesis modifies excitability of the dentate gyrus Frontiers in Neural Circuits, 7:204, 26 Dec 2013. doi: 10.3389/fncir.2013.00204
Purushothama Rao Tata, Hongmei Mou, Ana Pardo-Saganta, Rui Zhao, Mythili Prabhu, Brandon M. Law, Vladimir Vinarsky, Josalyn L. Cho, Sylvie Breton, Amar Sahay, Benjamin D. Medoff and Jayaraj Rajagopal. Dedifferentiation of committed luminal epithelial cells into functional stem cells in vivo. Nature 2013; 503(7475).
Mazen A. Kheirbek, Klemenhagen KC, Amar Sahay* and René Hen* (2012). Nat Neurosci, Nov;15(12):1613-20. Epub 2012 Nov 27. Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders. *Co-corresponding author.
Amar Sahay*, Kimberly N. Scobie, Alexis S. Hill, Colin M. O'Carroll, Mazen A. Kheirbek, Nesha S. Burghardt, André A. Fenton, Alex Dranovsky and René Hen* (2011). Nature, April 28; 472 (7344): 466-70. * Co-corresponding author. Covered in Leading edge, Cell 145, May 13, 2011. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.
Amar Sahay, Donald A. Wilson and René Hen (2011), Perspective, Special Issue: Reviews on stem cells and adult neurogenesis, Neuron, May 26, 70 (4), 582-588. Pattern separation: A common function for new neurons in hippocampus and olfactory Bulb.
Tillmann Weber, Vera Baier, Rahel Pauly, Amar Sahay, Max Baur, Elke Hermann, Francesca Ciccolini, René Hen, Golo Kronenberg and Dusan Bartsch (2011). Glia April; 59(4): 615-26. Inducible gene expression in GFAP+ progenitor cells of the SGZ and the dorsal wall of the SVZ– a novel tool to manipulate and trace adult neurogenesis.
Kimberly N. Scobie, Benjamin J. Hall, Scott A. Wilke, Kristen C. Klemenhagen, Yoshiaki Fujii-Kuriyama, Anirvan Ghosh, René Hen and Amar Sahay (2009). The Journal of Neuroscience August 5; 29(31): 9875-9887. Krüppel-like factor 9 (Klf-9) is necessary for late-phase neuronal maturation in the developing dentate gyrus and during adult hippocampal neurogenesis (Cover Image)
Amar Sahay* and René Hen (2007), Focus on Emotion and Disorders of Emotion issue. Nature Neuroscience 10(9):1110-1115. * Co-corresponding author. Adult hippocampal neurogenesis in depression
Amar Sahay, René Hen and Ronald S. Duman (2007). Adult Neurogenesis Cold Spring Harbor Monographs. Chapter: Hippocampal neurogenesis: Depression and Antidepressant responses.
Amar Sahay *, Chong-Hyun Kim *, Edward Cho, Jehuda Sepkuty, Richard L. Huganir, David D. Ginty and Alex L. Kolodkin (2005). The Journal of Neuroscience Apr 6; 25(14): 3613-20. Secreted semaphorins modulate synaptic transmission in the adult hippocampus (* equal contribution)
Jean-Francois Cloutier *, Amar Sahay *, Ernie C. Chang, Marc Tessier-Lavigne, Catherine Dulac, Alex L. Kolodkin and David D. Ginty (2004). The Journal of Neuroscience Oct 13; 24(41): 9087-9096. Distinct requirements for Semaphorin 3F and Slit-1 in axonal targeting, fasciculation and segregation of olfactory receptor sensory neuron projections (* equal contribution)
Amar Sahay, Mark E. Molliver, David D. Ginty and Alex L. Kolodkin (2003). The Journal of Neuroscience Jul 30; 23(17): 6671-80. Semaphorin 3F is critical for development of limbic system circuitry and is required in neurons for selective CNS axon guidance events.
Roman J. Giger, Jean-Francois Cloutier *, Amar Sahay *, Rabinder K. Prinjha* , Dorothy V. Levengood, Stephen E. Moore, Susan Pickering, David Simmons, Sohaila Rastan, Frank S. Walsh, Alex L. Kolodkin, David D. Ginty, and Martin Geppert (2000). Neuron 25, 29-41. Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins. (* equal contribution)