Cortical Mechanisms of Perceptual and Cognitive Development
How much of our behavior and its disorders are determined by our genes and by our environment? This nature-nurture debate has continued for centuries by both philosophers and scientists. We now know our behavior reflects neural circuits sculpted by experience during “critical periods” in postnatal life. Such heightened plasticity declines into adulthood, often limiting recovery of function. On the other hand, the adult brain needs stability. Failed stabilization can disrupt circuit computations by allowing modification by undesirable information, which may lead to mental disorders. How does the brain solve this stability-plasticity dilemma? The goal of our lab is to identify the mechanisms of developmental critical periods to establish (1) perception and (2) cognition relevant to neuro-developmental and psychiatric disorders. Our strategy is to use visual system, a premier model of critical period for cortical plasticity, to discover molecular/ circuit mechanisms, and then apply these mechanisms as unique tools to dissect more complicated critical periods for cognitive behaviors such as attention and social cognition. We are an active member of Center for Neurotechnology and Behavior and Center for Affective Neuroscience at Mount Sinai.
Experience-dependent Perceptual Development
Experience-dependent cortical plasticity is heightened during developmental critical periods but declines into adulthood, posing a major challenge to recovery of function following injury or disease later in life. Our research aims to identify the mechanisms of experience-dependent cortical plasticity. Using visual system, a premier model of critical period, we take an integrated approach, combining molecular, anatomical, imaging, electrophysiological methodologies (e.g. in vivo viral gene transfer, optogenetics, chemogenetics, and two-photon time lapse imaging). We also take translational bioinformatics approach to identify pro-plasticity drugs and anti-plastic perturbations. Our study would have direct implications for Amblyopia, a condition with limited adult-applicable treatment affecting 2–5% of the human population, but also for brain injury repair, sensory recovery, and the treatment of neurodevelopmental disorders.
Prefrontal Cortex-dependent Cognitive Development
Mechanisms driving critical period circuit development are well described in sensory cortex—but poorly characterized for prefrontal cortex dependent cognitive behaviors. Impaired prefrontal cortical connectivity is increasingly identified in a host of several neuropsychiatric disorders that coincides with this protracted developmental period. A second major goal of our research is to examine to what extent a mechanism regulating the critical period for visual cortex development also modulates maturation of prefrontal cortex-dependent cognitive functions such as attentional behavior, and social cognition. We aim to identify the developmental regulatory mechanism of cognitive function from the molecular, circuit to the behavioral level. Identified circuit-associated mechanisms would promote translation of our basic research findings to clinical research to improve diagnosis, prevention and treatment of neuro-developmental disorders.
Hirofumi Morishita M.D. Ph.D
Department of Psychiatry, Neuroscience, & Ophthalmology
Mindich Child Health & Development Institute
Friedman Brain Institute
Icahn School of Medicine at Mount Sinai
Postdoctoral Fellow/Graduate Student Positions Available
We are currently recruiting 2 postdocs or graduate students, 1 position each for the study of (1) circuit mechanism of cortical plasticity, and (2) social circuit maturation.
Special consideration will be given to applicants with experience in slice electrophysiology.
(1) Circuit Mechanisms of Cortical Plasticity: The goal of this position is to identify novel circuit mechanisms of experience dependent cortical plasticity using mouse visual system, a premier model of critical period. Potential project will combine slice patch-clamp recordings and in vivo electrophysiology with optogenetics, pharmacogenetics, and cell-type specific gain/loss of gene expression through genetic and viral techniques.
(2) Circuit Mechanisms of Social Processing Development: The goal of this position is to identify novel circuit and molecular mechanisms of social behavior maturation. Potential project will combine slice patch-clamp recordings, molecular study, optogenetics, pharmacogenetics, fiber photometry. Qualifications: PhD in neuroscience or relevant experience required. Past experience in slice electrophysiology is preferred. Experience with molecular biology, rodent in vivo analysis (e.g. stereotaxic surgery, behavior experiments, optogenetics), programing is a plus.
Application and required documents:
1) Cover letter, 2) Description of research experience, skills, & interests, 3) CV, 4) Names and contact information (email & tel) of 3 references with a brief description of your relationship to each reference. Please send the above information as a single pdf file to firstname.lastname@example.org
Hirofumi Morishita is an Associate Professor of Psychiatry, Neuroscience and Ophthalmology at the Icahn School of Medicine at Mount Sinai. He is also a faculty member of interdisciplinary Mindich Child Health & Development Institute, and Friedman Brain Institute. His research focuses on understanding the mechanisms of developmental critical periods for cortical maturation to establish perception and cognition relevant to neurodevelopmental and psychiatric disorders. His laboratory takes an integrated approach, combining molecular, anatomical, imaging, electrophysiological, and behavior methodologies using mouse models.
Hirofumi Morishita received his PhD from Osaka University after Psychiatry residency at National Center Hospital of Neurology and Psychiatry in Tokyo and medical school training at Kyushu University (MD). Before joining Mount Sinai, he was a postdoctoral research fellow at Takao Hensch lab, Children’s Hospital Boston, Harvard Medical School. His postdoctoral work led to the preclinical discovery of therapeutic strategies for functional recovery in adulthood (Morishita et al. Science 2010).
Awards & Honors
2016-: Associate Member, American College of Neuropsychopharmacology (ACNP)
2015: Inaugural Faculty Innovative Collaborations-Idea Prize, Icahn School of Medicine at Mount Sinai
2014: Travel Award: 47th Winder Conference on Brain Research
2012: Travel Award, American College of Neuropsychopharmacology (ACNP)
2017 – 2019: R21 NS105119 (BRAIN Initiative), National Institute of Neurological Disorders and Stroke
2017 – 2019: R21 EY026702, National Eye Institute
2015 – 2017: R21 MH106919, National Institute of Mental Health
2015 – 2018: R01 EY026053, National Eye Institute
2015 – 2020: R01 EY024918, National Eye Institute
2014, 2016: Mindich Child Health & Development Institute Pilot Grant
2013 – 2015: Basil O’Connor Starter Scholar Research Awards, March of Dimes
2012 – 2015: Research Grant, Whitehall Foundation
2012 – 2014: Early Career-Starter Research Grant, Knights Templar Eye Foundation
2012 – 2014: Young Investigator Award, National Alliance for Research on Schizophrenia and Depression (NARSAD)
Sadahiro, M.*, Demars, MP.*, Burman, P., Yevoo, P., Smith, MR., Zimmer, A., Morishita, H. (* equal contribution)
Activation of Somatostatin Inhibitory Neurons by Lypd6-nAChRα2 System Restores Juvenile-like Plasticity in Adult Visual Cortex.
BioRxiv doi: https://doi.org/10.1101/155465 (Pre-print).
Morishita, H*. Vinogradov, S*. (* corresponding authors)
Neuroplasticity and dysplasticity processes in Schizophrenia
Schizophrenia Research 2019 Mar 28. pii: S0920-9964(19)30090-8. PubMed
Smith M, , Dudley J, Morishita H
Critical period plasticity-related transcriptional aberrations in schizophrenia and bipolar disorder.
Schizophrenia Research 2018 Nov 12th, pii: S0920-9964(18)30623-6. PubMed
Smith M, Yevoo P, Sadahiro M, Arora M, Dudley J, Morishita H
Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity.
Scientific Reports Nov 6;8(1):16388. doi: 10.1038/s41598-018-34592-4, 2018. PubMed
Smith M, Glicksberg B, Li L, Chen R, *Morishita H, *Dudley J (* corresponding authors)
Loss-of-function of neuroplasticity-related genes confers risk for human neurodevelopmental disorders.
Pac Symp Biocomput 2018 23:68-79. PubMed
Jiang Y, Loh YE, Rajarajan P, Hirayama T, Liao W, Kassim BS, Javidfar B, Hartley BJ, Kleofas L, Park RB, Labonte B, Ho SM, Chandrasekaran S, Do C, Ramirez BR, Peter CJ, C W JT, Safaie BM, Morishita H, Roussos P, Nestler EJ, Schaefer A, Tycko B, Brennand KJ, Yagi T, Shen L, Akbarian S. The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain. Nature Genetics 2017 Jul 3. doi: 10.1038/ng.3906. PubMed
Steullet, P., Cabungcal, J., Coyle, J., Didriksen, M., Gill, K., Grace, A., Hensch, T., LaMantia, A., Lindemann, L., Maynard, T., Meyer, U., Morishita, H., O’Donnell, P., Puhl, M., Cuenod, M., Do, KQ. Oxidative stress-driven parvalbumin interneuron impairment as a core mechanism in models of psychiatric disorders. Molecular Psychiatry 2017 Jul;22(7):936-943. PubMed
Morishita, H., Arora, M. Tooth-matrix biomarkers to reconstruct critical periods of brain plasticity. Trends in Neurosciences 2017. Jan 27; 40 (1):1-3. Pubmed # Video clip: Tooth Biomarkers Reconstruct Brain Plasticity
Smith, M., Burman, P., Sadahiro, M., Kidd, B., Dudley, J., Morishita, H. Integrative analysis of disease signatures shows inflammation disrupts juvenile experience-dependent cortical plasticity eNeuro 2017 Jan 18. 3 (6). Pubmed
Sadahiro, M., Sajo, M., Morishita, H.
Nicotinic regulaiton of experience-dependent plasticity in visual cortex
Journal of Physiology-Paris 2016 Nov 10th, Review. Pubmed
Sajo, M., Ellis-Davies, G.C., Morishita, H.
Lynx1 limits dendritic spine turnover in the adult visual cortex
Journal of Neuroscience 2016 Sep7, 36(36):9472-9478 Pubmed
Mitchell, A.C., Javidfar, B., Bicks, L.K., Neve, R., Garbett, K., Lander, S.S., Mirnics, K., Morishita,H., Wood, M.A., Jiang, Y., Gaisler-Salomon, I., Akbarian, S.
Longitudinal Assessment of Neuronal 3D Genomes in Mouse Prefrontal Cortex.
Nature Communications 2016 Sep 6;7:12743. PubMed
Lucas, E.K., Jegarl, A.M., Morishita, H., Clem, R.L.
Multimodal and site-specific plasticity of amygdala parvalbumin interneurons after fear learning
Neuron 2016 2016 Aug 3;91(3):629-43. PubMed
Koike, H., Demars, M.P., Short, J.A., Nabel, E.M., Akbarian, S., Baxter, M.G., Morishita, H.
Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse.
Neuropsychopharmacology 2016. Mar, 41 (4) 1014-23, doi: 10.1038/npp.2015.229. PubMed
Bicks, L., Koike, H., Akbarian, S., Morishita,H.
Prefrontal cortex and social cognition in mouse and man
Frontiers in Psychology. Front. Psychol. | doi: 10.3389/fpsyg.2015.01805. Review.PubMed
Bukhari, N., Burman, P., Hussein, A., Demars, M.P., Sadahiro, M., Brady, D., Tsirka, S.E., Russo, S.J., Morishita, H.
Unmasking proteolytic activity for adult visual cortex plasticity by the removal of Lynx1.
Journal of Neuroscience 2015. Sep 16;35(37):12693-702. PubMed
Morishita, H., Kundakovic, M., Bicks, L., Mitchell, A., Akbarian, S.
Interneuron Epigenomes duing the Critical Period of Cortical Plasticity: Implications for Schizophrenia.
Neurobiology of Learning and Memory.2015 Oct;124:104-10. Review.PubMed
Morishita, H., Cabungcal, J., Chen, Y., Do, KQ., Hensch, TK.
Prolonged period of cortical plasticity upon redox dysregulation in fast-spiking interneurons.
Biological Psychiatry Sep 15;78(6):396-402.PubMed
Demars, MP., Morishita, H.
Cortical parvalbumin and somatostatin GABA neurons express distinct endogenous modulators of nicotinic acetylcholine receptors. Molecular Brain 2014 Oct 31;7(1):75. PubMed
Nabel E, Morishita H.
Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions.
Front. Psychiatry 2013 Nov 11: 4: 146. Review PubMed
Sajo, M., Morishita, H.
Critical Period Mechanisms: Implication for Neurodevelopmental and Psychiatric Disorders.
Brain and Nerve 2013; 65(10) 1159-66. Review PubMed
Cabungcal JH, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch TK, Do KQ.
Perineuronal nets protect fast-spiking interneurons against oxidative stress.
Proc Natl Acad Sci U S A. 2013 May 13. 110 (22) 9130-5: PubMed
# Safety Net: Perineuronal Nets Protect Interneurons Linked to Schizophrenia
Research News in Schizophrenia Research Forum
# Damaged Protective ‘Net’ May Cause Malfunction in Brain Cells in Schizophrenia
Discoveries in Brain & Behavior Research Foundation
Molecular Strategies for Recovery from Amblyopia.
Ophthalmology 013; 55(1) 23-28. Review
Cholinergic contribution on visual cortex plasticity.
Clinical Neuroscience 2012; 30(6) 649-651. Review
Molecularly targeted therapeutic strategies for Amblyopia
NeuroOphthalmol 2012; 29(4) 389-395. Review
Morishita, H., Miwa, JM., Heintz, N., Hensch, TK..
Lynx1, a cholinergic brake limits plasticity in adult visual cortex.
Science 2010 Nov 26; 330(6008):1238-40. view in: PubMed
# Perspective by Higley MJ, Strittmatter SM.
Science. 2010 Nov 26; 330(6008):1189-90.
# Editor’s Choice by Hines PJ. Science Signaling
2010 Nov 30
# Understanding the brain’s “Brake Pedal” in Neural
Plasticity. Scientific American. 2011 Feb 22.
# Removing an Endogenous Prototoxin Restores Vision.
Harvard MCB News. 2010 Dec 9.
# Alzheimer’s drugs for “lazy eye”?
Children’s Hospital Boston’s science and
clinical innovation blog. 2010 Dec 16.
# Supported by the James S. McDonnell Foundation
“Recovery from Amblyopia” network
Morishita, H., Hensch, TK.
Critical period revisited: impact on vision.
Current Opinion in Neurobiology. 2008 Feb; 18(1):101-7. Review. view in: PubMed
Morishita, H.*, Yagi, T.*. (*co-corresponding authors)
Protocadherin family: diversity, structure, and function.
Current Opinion in Cell Biology. 2007 Oct; 19(5):584-92. Review. view in: PubMed
Morishita, H.*, Umitsu, M.*, Murata, Y., Shibata, N., Udaka, K., Higuchi, Y., Akutsu, H., Yamaguchi T, Yagi, T., Ikegami, T.
Structure of the cadherin-related neuronal receptor/protocadherin-alpha first extracellular cadherin domain reveals diversity across cadherin families.
Journal of Biological Chemistry. 2006 Nov 3; 281(44):33650-63. view in: PubMed
# Evaluated by Faculty of 1000 Biology
Umitsu, M.*,Morishita, H.*, Murata, Y., Udaka, K., Akutsu, H., Yagi, T., Ikegami, T. (* equal first authors)
1H, 13C and 15N resonance assignments of the first cadherin domain of Cadherin related neuronal receptor/Protocadherin α.
Journal of Biomolecular NMR. 2005, Apr; 31(4):365-6. view in: PubMed
Morishita, H., Murata, Y., Esumi, S., Hamada, S., Yagi, T.
CNR/Pcdhα family in subplate neurons, and developing cortical connectivity.
Neuroreport. 2004 Dec 3; 15(17): 2595-2599. view in: PubMed
Morishita, H., Kawaguchi, M., Murata, Y., Seiwa, C., Hamada, S., Asou, H., Yagi, T.
Myelination triggers local loss of axonal CNR/Protocadherinα family expression.
European Journal of Neuroscience. 2004 Dec 2; 20(11): 2843-2847. view in PubMed
Murata, Y., Hamada, S., Morishita, H., Mutoh, T., Yagi, T.
Interaction with Protocadherin-g regulates the cell-surface expression of Protocadherin-α.
Journal of Biological Chemistry. 2004 Nov 19;279(47): 49508-49516. view in PubMed
Tada, M., Senzaki, K., Tai, Y., Morishita, H., Tanaka, Y., Murata, Y., Ishii, Y., Asakawa, S., Shimizu, N., Sugino, H., Yagi, T.
Genomic organization and transcripts of the zebrafish Protocadherin genes.
Gene. 2004 Oct 13; 340(2):197-211. view in PubMed
Morishita, H., Makishima, T., Kaneko, C., Lee, YS., Segil, N., Takahashi, K., Kuraoka, A., Nakagawa, T., Nabekura, J., Nakayama, K., Nakayama, KI.
Deafness due to degeneration of cochlear neurons in caspase-3-deficient mice.
Biochemical and Biophysical Research Communications. 2001 Jun 1; 284(1):142-9. view in PubMed
Hirofumi Morishita MD PhD
Yury Garkun PhD
(with Morishita & Joel Dudley lab)
(with Morishita and Akbarian Lab)
Christina (Na Yun) Cho
We accept rotation students from
Mount Sinai PhD, MD-PhD, MD, & MS programs
For postdoc position, please contact
One Gustave L. Levy Place Box1230
New York, NY 10029
1470 Madison Avenue
Hess Center 9-301 (lab), 9-113 (office)
New York, NY 10029