Autism, Behavior, Cerebral Cortex, Cognitive Neuroscience, Developmental Neurobiology, Molecular Biology, Neural Networks, Neuromodulation, Neurophysiology, Oxidative Stress, Prefrontal Cortex, Schizophrenia, Synaptic Plasticity, Systems Neuroscience, Vision
National Eye Institute R01 EY026053
National Institute of Health
National Eye Institute R01 EY024918
National Institute of Health
Inaugural Faculty Innovative Collaborations-Idea Prize
Icahn School of Medicine at Mount Sinai
National Institute of Mental Health R21 MH106919
National Institute of Health
Mindich Child Health & Development Institute Pilot Grant
Basil O'Connor Starter Scholar Research Awards
March of Dimes
American College of Neuropsychopharmacology (ACNP)
Young Investigator Award
National Alliance for Research on Schizophrenia and Depression (NARSAD)
Early Career-Starter Research Grant
Knights Templar Eye Foundation
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 neurodevelopmental and psychiatric disorders. We take an integrated approach combining molecular, anatomical, imaging, electrophysiological, and behavior methodologies using mouse models.
Mechanisms Regulating 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. The major goal of our research is 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 all in vivo by further incorporating advanced techniques such as 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 with sensory perceptual deficits such as autism. Currently our focus is on two regulatory systems of cortical plasticity: (1) endogenous nicotinic ACh Receptor regulators, and (2) proteolytic system.
Mechanisms Regulating Prefrontal Cortex-dependent Cognitive Development
Mechanisms driving critical period circuit development are well described in sensory systems—but poorly characterized for complex cognitive behaviors. Identification of a critical period and underlying mechanisms for cognitive circuits and behavior would eventually improve diagnosis, prevention and treatment of psychiatric disorders. Our study aims to examine to what extent a mechanism critical for regulating the critical period for visual cortex development also modulates maturation of frontal cortex-dependent cognitive functions such as attention and social cognition. We combine in vivo circuit-specific manipulations with a translationally-relevant touchscreen behavioral testing system to identify the developmental regulatory mechanism of cognitive function from the molecular, circuit to the behavioral level. For this line of research, we actively collaborate with division of psychiatric genomics, neurodevelopmental disorders, and psychiatric epigenomics at Mount Sinai.
Mari Sajo PhD: Postdoctoral Fellow
Yury Garkun PhD: Postdoctoral Fellow
Milo Smith: PhD Student
Masato Sadahiro: PhD Student
Elisa Nabel: MDPhD Student
Lucy Bicks: PhD Student
Giulia Taccheri: Master Student
Susanna Im: Master Student
Sarah Lopez: Associate Researcher
Priscilla Yevoo: Associate Researcher
Michelle Peng: Associate Researcher
Sajo M, Ellis-Davies G, Morishita H. Lynx1 Limits Dendritic Spine Turnover in the Adult Visual Cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 2016 Sep; 36(36).
Mitchell AC, Javidfar B, Bicks LK, Neve R, Garbett K, Lander SS, Mirnics K, Morishita H, Wood MA, Jiang Y, Gaisler-Salomon I, Akbarian S. Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex. Nature communications 2016 Sep; 7.
Lucas EK, Jegarl AM, Morishita H, Clem RL. Multimodal and Site-Specific Plasticity of Amygdala Parvalbumin Interneurons after Fear Learning. Neuron 2016 Jul;.
Bicks LK, Koike H, Akbarian S, Morishita H. Prefrontal Cortex and Social Cognition in Mouse and Man. Frontiers in psychology 2015 Nov; 6.
Bukhari N, Burman PN, Hussein A, Demars MP, Sadahiro M, Brady DM, Tsirka SE, Russo SJ, Morishita H. Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1. The Journal of neuroscience : the official journal of the Society for Neuroscience 2015 Sep; 35(37).
Koike H, Demars MP, Short JA, Nabel EM, Akbarian S, Baxter MG, Morishita H. Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2015 Jul;.
Morishita H, Kundakovic M, Bicks L, Mitchell A, Akbarian S. Interneuron epigenomes during the critical period of cortical plasticity: Implications for schizophrenia. Neurobiology of learning and memory 2015 Apr;.
Morishita H, Cabungcal JH, Chen Y, Do KQ, Hensch TK. Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons. Biological psychiatry 2015 Jan;.
Demars MP, Morishita H. Cortical parvalbumin and somatostatin GABA neurons express distinct endogenous modulators of nicotinic acetylcholine receptors. Molecular brain 2014 Oct; 7(1).
Nabel EM, Morishita H. Regulating critical period plasticity: insight from the visual system to fear circuitry for therapeutic interventions. Frontiers in psychiatry 2013 Nov; 4.
Morishita H, Miwa JM, Heintz N, Hensch TK. Lynx1, a cholinergic brake, limits plasticity in adult visual cortex. Science (New York, N.Y.) 2010 Nov; 330(6008).
Cabungcal JH, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch TK, Do KQ. Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proceedings of the National Academy of Sciences of the United States of America 2013 May; 110(22).
Morishita H, Hensch TK. Critical period revisited: impact on vision. Current opinion in neurobiology 2008 Feb; 18(1).
Morishita H, Yagi T. Protocadherin family: diversity, structure, and function. Current opinion in cell biology 2007 Oct; 19(5).
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. The Journal of biological chemistry 2006 Nov; 281(44).
Umitsu M, Morishita H, Murata Y, Udaka K, Akutsu H, Yagi T, Ikegami T. 1H, 13C and 15N resonance assignments of the first cadherin domain of Cadherin-related neuronal receptor (CNR)/protocadherin alpha. Journal of biomolecular NMR 2005 Apr; 31(4).
Morishita H, Kawaguchi M, Murata Y, Seiwa C, Hamada S, Asou H, Yagi T. Myelination triggers local loss of axonal CNR/protocadherin alpha family protein expression. The European journal of neuroscience 2004 Dec; 20(11).
Morishita H, Murata Y, Esumi S, Hamada S, Yagi T. CNR/Pcdhalpha family in subplate neurons, and developing cortical connectivity. Neuroreport 2004 Dec; 15(17).
Tada MN, Senzaki K, Tai Y, Morishita H, Tanaka YZ, Murata Y, Ishii Y, Asakawa S, Shimizu N, Sugino H, Yagi T. Genomic organization and transcripts of the zebrafish Protocadherin genes. Gene 2004 Oct; 340(2).
Murata Y, Hamada S, Morishita H, Mutoh T, Yagi T. Interaction with protocadherin-gamma regulates the cell surface expression of protocadherin-alpha. The Journal of biological chemistry 2004 Nov; 279(47).
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; 284(1).
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Dr. Morishita has not yet completed reporting of Industry relationships.
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