Adult-born hippocampal neurons in cognition and affective behaviors
Although the maturation of the mammalian brain is marked by the progressive restriction of cellular and neural plasticity, it is now widely recognized that the dentate gyrus sub region of the hippocampus is host to neurogenesis, the generation of functional neurons from neural stem cells, throughout life. Our research seeks to: (i) Characterize the regulatory mechanisms that control adult hippocampal neurogenesis, (ii) Identify molecular programs that define the properties and connectivity of new neurons, and (iii) Interrogate how stem cells and adult-born neurons function within the hippocampal circuit to influence learning and emotional behavior of normal mice and murine models of psychiatric illness.
Neural mechanisms underlying psychiatric illnesses
Most, if not all, psychiatric illnesses have their origins in the disruption of genetic and epigenetic programs that dictate embryonic and early-post natal development of neural circuits. We want to understand how alterations in neural circuits during the early postnatal period, when environment refines behaviors, contribute to perturbed affective behaviors and impairments in cognitive functions in adulthood.
Towards these goals, we employ a combination of viral and mouse genetic based molecular-, pharmaco- and opto-genetic techniques to manipulate neural stem cells and distinct cell types, as well as candidate genes that we have identified, with concomitant assessment of circuit function and behavior. It is hoped that our efforts will shed light on: (i) The therapeutic potential of targeting adult neurogenesis for treatment of cognitive impairments and mood dysfunction, (ii) The identification of latent mechanisms of plasticity extant in other regions of the adult mammalian brain, and (iii) Etiological mechanisms underlying psychiatric illnesses.
Sally Levinson, B.S (Ph.D. program in Neuroscience at NYU, 2013-)
Tomer Langberg, B.S. (2013- )
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)
Shannen Kim (Harvard)
Melissa Boldridge (Harvard)
Visiting students and fellows
Paoyan Lin, Medical Student (Karolinska Insitute)
Sreyan Chowdhury (College of Wooster)
For research opportunities please contact Dr. Amar Sahay.
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)