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Postdoctoral Fellow

Saurav Seshadri, Ph.D.

Section on Critical Brain Dynamics

Laboratory of Systems Neuroscience
Building 35 Room 3A-116
35 Convent Drive
Bethesda MD 20892-3726
Office: (301) 594-8060
Lab: (301) 451-9616
Fax: (301) 480-7480

I am currently a postdoctoral fellow in the lab of Dr. Dietmar Plenz, in the Section on Critical Brain Dynamics at NIMH.  I received my Ph.D. in Cellular and Molecular Medicine under the mentorship of Dr. Akira Sawa, in the Department of Psychiatry at Johns Hopkins University.  I am experienced in molecular biology, 2-photon imaging and optogenetics, transgenic and pharmacological disease models, and computational neuroscience.   

As a graduate student and postdoctoral fellow, I studied pathological mechanisms in schizophrenia, at the level of genes, molecules, cells, circuits, networks, and behavior.  My main research interest is in characterizing the network-level dysfunction that translates genetic abnormalities into cognitive impairment.  My approach to this topic is based on performing targeted disruptions of molecular functioning in model animals, and identifying phenotypes in the higher order interactions of cortical neurons, by recording population activity with cellular resolution and applying established, theory-driven analysis methods.  I believe that this strategy can provide insight into the cell type-specific deficits underlying disease-associated network dysfunction, as well as into network dynamics that influence cognitive performance.  These phenotypes can also serve as a platform to test mechanistic hypotheses and therapeutic interventions. 

My recent work has focused on pharmacological models of schizophrenia.  By performing in vivo 2-photon imaging of genetically encoded calcium indicators, as well as behavioral testing, in these animals, I can characterize the network-level phenotypes that bridge molecular dysfunction (e.g., NMDAR hypofunction induced by PCP treatment) and cognitive impairment (e.g., deficient working memory).  I can also study the mechanisms associated with these phenotypes, by testing the effects of interventions at the molecular (e.g., treatment with NMDAR co-agonist D-serine) or cellular (e.g., optogenetic inhibition of fast-spiking interneurons) levels.  By combining these experimental paradigms with neuronal avalanche analysis, based on the theory of criticality in neural systems, I am working to discover new biomarkers for schizophrenia and determine their underlying causes.

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  • 1) Seshadri, S., Bellay, T., Klaus, A., Winkowski, D., Plenz, D. (2016)
  • Altered Cortical Dynamics in a Rodent Model of Schizophrenia
  • In preparation
  • 2) Seshadri, S., Ishizuka, K., Faust, T., Delevich, K., Chung, Y., Kim, S.H., Cowles, M., Niwa. M, Jaaro-Peled, H., Tomoda, T., Lai, C., Anton, E., Li, B., Sawa, A (2015)
  • Interneuronal DISC1 Regulates NRG1-ErbB4 Signaling and Excitatory-Inhibitory Circuit Functioning in the Mature Cortex.
  • Nat Commun, 6:10118
  • 3) Bellay, T., Klaus, A., Seshadri, S., Plenz, D. (2015)
  • Irregular Spiking of Pyramidal Neurons Organizes as Scale-Invariant Neuronal Avalanches in the Awake State.
  • eLife, 4:e07224. DOI: 10.7554/eLife.07224
  • 4) Shahani, N., Seshadri, S., Jaaro-Peled, H., Ishizuka, K., Hirota-Tsuyada, Y., Wang, Q., Koga, M., Sedlak, T.W., Korth, C., Brandon, N.J., Kamiya, A., Subramaniam, S., Tomoda, T., Sawa, A. (2014)
  • DISC1 Regulates Trafficking and Processing of APP and Aβ Generation.
  • Mol. Psychiatry, 20(7):874-9. doi: 10.1038/mp.2014.100. Epub 2014 S
  • 5) Niwa, M., Jaaro-Peled, H., Tankou, S., Seshadri, S., Hikida, T., Matsumoto, Y., Cascella, N.G., Kano, S., Ozaki, N., Nabeshima, T., Sawa, A. (2013)
  • Adolescent Stress-Induced Epigenetic Control of Dopaminergic Neurons via Glucocorticoids.
  • Science, 18:339 (6117):335-9
  • 6) Seshadri, S., Zeledon. M., Sawa, A. (2013)
  • Synapse-Specific Contributions in the Cortical Pathology of Schizophrenia.
  • Neurobiol. Dis. , 53, 26-35
  • 7) Ishizuka, K., Kamiya, A., Oh, E. C., Kanki, H., Seshadri, S., Robinson, J. F., Murdoch, H., Dunlop, A. J., Kubo, K., Furukori, K., Huang, B., Zeledon, M., Hayashi-Takagi, A., Okano, H., Nakajima, K., Houslay, M. D., Katsanis, N., Sawa, A. (2011)
  • DISC1-Dependent Switch from Progenitor Proliferation to Migration in the Developing Cortex.
  • Nature, 473, 92-96
  • 8) Hayashi-Takagi, A., Takaki, M., Graziane, N., Seshadri, S., Murdoch, H., Dunlop, A.J., Makino, Y., Seshadri, A.J., Ishizuka, K., Srivastava, D.P., Xie, Z., Baraban, J.M., Houslay, M.D., Tomoda, T., Brandon, N.J., Kamiya, A., Yan, Z., Penzes, P., Sawa, A. (2010)
  • Disrupted-in-Schizophrenia 1 (DISC1) Regulates Spines of the Glutamate Synapse via Rac1.
  • Nat Neurosci, 13, 327-332
  • 9) Niwa, M., Kamiya, A., Murai, R., Kubo, K., Gruber, A.J., Tomita, K., Lu, L., Tomisato, S., Jaaro-Peled, H., Seshadri, S., Hiyama, H., Huang, B., Kohda, K., Noda, Y., O'Donnell, P., Nakajima, K., Sawa, A., Nabeshima, T. (2010)
  • Knockdown of DISC1 by In Utero Gene Transfer Disturbs Postnatal Dopaminergic Maturation in the Frontal Cortex and Leads To adult Behavioral Deficits
  • Neuron, 65, 480-489
  • 10) Seshadri, S., Kamiya, A., Yokota, Y., Prikulis, I., Kano, S., Hayashi-Takagi, A., Stanco, A., Eom, T. Y., Rao, S., Ishizuka, K., Wong, P., Korth, C., Anton, E. S., Sawa, A. (2010)
  • Disrupted-in-Schizophrenia-1 Expression Is Regulated by Beta-Site Amyloid Precursor Protein Cleaving Enzyme-1-Neuregulin Cascade.
  • Proc Natl Acad. Sci. U S A, 107, 5622-5627
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