Faculty Detail   
Name KAZUTOSHI NAKAZAWA
  
Campus Address SHEL 1010 Zip 2182
Phone  (205) 934-0742
E-mail  nakazawk@uab.edu
Other websites
    

 Education

Medical School  Keio University School of Medicine     1987  MD 
Graduate  Keio University School of Medicine     1991  PhD 
Fellowship  Riken Brain Science Institute     1995  Postdoctoral Fellow 
Fellowship  Massachusetts Institute of Technology    2003  Research Fellow/Associate 

Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Neurobiology  Neurobiology Associate Professor Adjunct

Biographical Sketch 
Dr. Kazu Nakazawa attended medical school at the Keio University School of Medicine in Tokyo, Japan. He received his M.D. and Ph.D. degrees from the Department of Microbiology at Keio in 1991 where he worked with Dr. Hisashi Narimatsu studying the molecular diversity of mammalian glycosyltransferases. He began his post-doctoral training in the Laboratory for Neural Networks, Frontier Research Programs at the RIKEN Institute, Wako, Japan. There he focused on the molecular and cellular mechanisms of cerebellar long-term depression under Professor Masao Ito. In 1995, he moved to the Center for Learning and Memory at MIT as a research fellow and became a research associate in 2000. At MIT, he studied the molecular mechanism of hippocampal learning and memory, in particular, pattern completion, under Professor Susumu Tonegawa. In 2003 he moved to NIMH Intramural Program as a faculty member, where he began studying pathophysiology of major neuropsychiatric illnesses by modeling in mice. Dr. Nakazawa joined the faculty of the Department of Psychiatry and Behavioral Neurobiology at the University of Alabama at Birmingham in September 2013. His lab is focused on the identification of critical mechanisms that regulate maturation of cortical and hippocampal interneuron circuitry and to specify how abnormalities in these systems lead to mental disorders.

Society Memberships
Organization Name Position Held Org Link
Society for Neuroscience  Member  http://www.sfn.org  
 

Research/Clinical Interest
Title
NMDA Receptors, GABAergic interneurons, and neuropsychiatric illnesses
Description
Nearly a century ago, Santiago Ramon y Cajal called interneurons 'mysterious butterflies of the soul'. In recent years, this prescient metaphor has been amply borne out by experiments suggesting that such basic mental functions as memory, cognition, attention, and perception depend on cortical interneurons maintaining the proper excitatory-inhibitory balance. Disruptions of this balance, moreover, are implicated in the development of mental disorders. To investigate the neural foundations of mental function and the causes of mental disorders, we focus on GABAergic interneurons' role in cortical development, especially during the perinatal and early postnatal periods. Critically, we have discovered schizophrenia-like phenotypes in mice deprived, during early postnatal development, of glutamatergic NMDA receptors (NMDARs) in cortical and hippocampal interneurons, a majority of which are parvalbumin-positive. This finding has driven our current and future research focus. Our first research goal is to delineate the downstream pathways of NMDAR deletion in GABAergic neurons, which may be responsible for positive, negative, and cognitive symptoms, through genetically dissecting the changes in the molecular and cellular processes. Our second goal is to identify the specific dysfunctions which occur during embryonic development that lead to the NMDAR hypofunction in the cortical interneurons. In turn, these studies may uncover the physiological mechanisms by which normal cortical network refinement occurs during development. Overall, our research aim is, relying on a multidisciplinary approach, using the techniques of mouse genetics, immunocytochemistry, slice physiology, cellular neurobiology, in vivo tetrode recording, and mouse behavioral analysis, to create and use mouse models to address these key questions with the ultimate goal of identifying objective neurobiological markers for human schizophrenia.

Selected Publications 
Nakao, K. and Nakazawa, K. (2014) Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model. Frontiers in Neuroscience 168: doi: 10.3389/fnins.2014.00168  25018691 
Jiang Z, Cowell RM and Nakazawa K (2013) Convergence of genetic and environmental factors on parvalbumin-positive interneurons in schizophrenia. Front. Behav. Neurosci. 7:116. doi:10.3389/fnbeh.2013.00116  24027504 
Brigman, J.L., Graybeal, C., Wright, T., Davis, M., Daut, R., Jiang, Z., Jinde, S., Saksida, L., Pease, M., Bussey, T.J., Lovinger, D.M., Nakazawa, K., and Holmes, A. (2013) GluN2B in corticostriatal circuits governs choice learning and shifting. Nat Neurosci 16, 1101-1110.  23831965 
Rompala, G.R., Zsiros, V., Zhang, S., Kolata, S.M., and Nakazawa, K. (2013) Contribution of GluN1 Deletion in Prefrontal and Cortical Sensory Excitatory Cells to Schizophrenia-like Phenotypes. PLOS ONE 8, e61278.  23613827 
Jinde, S., Zsiros, V, and Nakazawa, K. (2013) Hilar mossy cell circuitry controlling dentate granule cell excitability. Front. Neural Circuits 7:14. doi: 10.3389/fncir.2013.00014   23407806 
Jiang, Z., Rompala, G.R., Zhang, S., Cowell, R.M., and Nakazawa, K. (2013) Social Isolation Exacerbates Schizophrenia-like Phenotypes via Oxidative Stress in Cortical Interneurons. Biol Psychiatry 73, 2014-1034.  23348010 
Jinde, S., Zsiros, V., Jiang, Z., Nakao, K., Kohno, K., Belforte, J.E., and Nakazawa, K. (2012) Hilar Mossy Cell Degeneration Causes Transient Dentate Granule Cell Hyperexcitability and Impaired Pattern Separation. Neuron 76, 1189-1200.   23259953 
Malkesman, O., Austin, D.R., Tragon, T., Wang, G., Rompala, G., Hamidi, H.B., Cui, Z., Young, W.S., Nakazawa, K., Zarate, C.A., Manji, H.K., and Chen, G. (2012) Acute D-serine treatment produces antidepressant-like effects in rodent models of depression. International Journal of Neuropsychopharmacology 15, 1135-1148.   21906419 
Nakazawa, K., Zsiros, V., Jiang, Z., Nakao, K., Kolata, S., Zhang, S., and Belforte, J.E. (2012) GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology 62, 1574-1583.  21277876 
Christian, K.M. Miracle, A.D., Wellman, C.L., and Nakazawa, K. (2011) Chronic stress-induced hippocampal dendritic retraction requires CA3 NMDA receptors. Neuroscience 174, 26-36.  21108993 
Jiang, Z., Belforte, J.E., Lu, Y., Yabe, Y., Pickel, J., Smith, C.B., Je, H.-S., Lu, B., and Nakazawa K. (2010) eIF2alpha phosphorylation-dependent translation in CA1 pyramidal cells impairs hippocampal memory consolidation without affecting general protein synthesis J. Neurosci. 30, 2582-2594.  20164343 
Belforte, J.E., Zsiros, V., Sklar, E.R., Jiang, Z., Yu, G., Li, Y., Quinlan, E.M., and Nakazawa, K. (2010) Postnatal NMDA Receptor Ablation in Corticolimbic Interneurons Confers Schizophrenia-like Phenotypes. Nat. Neurosci. 13, 76-83. Epub 2009 Nov 15 (associated with a featured preview article in the January 2010 issue).  19915563 
Jinde, S., Belforte, J.E., Yamamoto, J., Wilson, M.A., Tonegawa, S., and Nakazawa K. (2009) Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death. Eur. J. Neurosci. 30, 1036-1055.  19735292 
Cravens, C.J., Vargas-Pinto, N., Christian, K.M., and Nakazawa, K (2006) CA3 NMDA Receptors are Crucial for Rapid and Automatic Representation of Context Memory. Eur. J. Neurosci. 24, 1771-1780.  17004940 
Nakazawa, K., McHugh, T.J., Wilson, M.A., and Tonegawa, S. (2004) NMDA Receptors, Place Cells and Hippocampal Spatial Memory. Nature Rev. Neurosci. 5, 361-372.  15100719 
Nakazawa, K., Sun, L.D., Quirk, M.C., Rondi-Reig, L., Wilson, M.A., and Tonegawa, S. (2003) Hippocampal CA3 NMDA receptors are crucial for memory acquisition of one-time experience. Neuron 38, 305-315.  12718863 
Nakazawa, K., Quirk, M.C., Chitwood, R.A., Watanabe, M., Yeckel, M.F., Sun, L.D., Kato, A., Carr, C.A., Johnston, D., Wilson, M.A., and Tonegawa, S. (2002) Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297, 211-218.  12040087 
 

Keywords
Schizophrenia, depression, stress, psychosis, NMDA receptor, interneuron, synchronous oscillation, dopamine, transgenic mice