disorders, including autism, epilepsy, mental retardation, and
neuropsychiatric disorders that include schizophrenia and anxiety.
Dr. Levitt?s laboratory investigates the molecular and cellular mechanisms underlying the development of circuits that are involved in cognitive and social-emotional behavior and mood regulation. These basic developmental neurobiological studies are designed to investigate the molecular and developmental basis of neuropsychiatric and developmental disorders, including schizophrenia, anxiety, attentional deficit hyperactivity and mental retardation. The laboratory addresses long-standing issues, such as early pattern formation in the forebrain, control of neural cell fate, molecular mechanisms of axon-target recognition and cell-cell interactions that are required for growth, differentiation and survival of cortical and other forebrain neurons. For example, studies pursue the role of growth factors and other signaling molecules that are involved in controlling cell phenotype and cell migration. Experience independent and dependent aspects of postnatal forebrain development is investigated using molecular and behavioral approaches. The study of novel genes provides opportunities for us to perturb specific aspects of development using gene knockout and transgenic technology in mice. The structural and functional consequences of induced developmental defects are examined using viral trans-synaptic tracing, cell-based assays and behavioral analysis. The laboratory also uses genetic tools to investigate the molecular alterations that underlie specific psychopathologies. Gene microarray and proteomic technology is applied to regional and individual cellular analyses of changes in gene expression in specific circuits of the diseased human brain and in experimental model systems. The laboratory also has a major effort in studying the behavioral and circuitry problems that arise from abnormal brain development following in utero exposure to drugs of abuse. Modified neurotransmitter and receptor activities are examined from basic developmental and cellular perspectives, and long-term changes in function are investigated with modern cellular, neuroanatomical and phrarmacological tools.
Levitt, P. Structural and functional maturation of the developing primate brain. J. Pediatrics, 10, S35-S45, 2003
Powell, E.M., Campbell, D.B., Stanwood, G.D., Davis, C., Noebels, J.L., and Levitt, P. Genetic Disruption of cortical interneuron development causes region- and GABA cell type-specific deficits, epilepsy, and behavioral dysfunction. J. Neurosci., 23(2), 622-631, 2003
Stanwood, G.D., Levitt, P. Repeated intravenous cocaine exposure produces long-lasting behavioral sensitization in pregnant adults, but behavioral tolerance in their offspring. Neuroscience, 122, 579-583, 2003
Middleton,F.A., Mirnics,K., Pierri,J.N., Lewis,D.A. and Levitt, P.. Gene Expression Profiling Reveals Alterations of Specific Metabolic Pathways in Schizophrenia. The Journal of Neuroscience, 22(7), 2718-2729, 2002
Uziel, D., Muhlfriedel S., Zarbalis, K., Wurst, W., Levitt, P., Bolz, J.. Miswiring of Limbic Thalamocortical Projections in the Absence of Ephrin-A5. The Journal of Neuroscience, 22(21), 9352-9357, 2002