Center for Regenerative Medicine, Department of Psychiatry
185 Cambridge Street
Boston, MA 02114
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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 link them with specific mnemonic processes (iii) Interrogate how stem cells and adult-born neurons function within the hippocampal circuit to influence learning and affective behaviors.
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.
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.
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
For a complete listing of publications click here.
Last Update: 7/26/2012