Schizophrenia is one of the most debilitating psychiatric disorders, affecting approximately 1% of the population worldwide. A number of antipsychotic drugs are available but these are often ineffective and do not treat all the symptoms of the disease. New therapeutics are needed but their discovery has been hampered by a limited understanding of the etiology of this complex neurological disorder, and a lack of clear understanding of the precise molecular mechanisms of action of available antipsychotic drugs. One of the major limitations in identifying the molecular mechanisms of antipsychotic drug action has been the heterogeneous and intermixed cellular nature of the central nervous system. The major goal of the proposed studies in the Conte Center is therefore to achieve a complete understanding of the cellular and molecular actions of antipsychotic drugs through innovative approaches that use novel rodent animal models to allow analysis of individual types of neurons within cortico-striatal circuits. The Center Director and leader of Project 1 is Paul Greengard (Rockefeller University). The other Project leaders are: Nathaniel Heintz (Project 2, Rockefeller University);Angus Nairn (Project 3, Yale University);Eric Nestler (Project 4, Mount Sinai Medical School);and James Surmeier (Project 5, Northwestern University. There will also be an Animal Core, a Molecular &Biochemical Reagents Core, and an Administrative Core. The five Pis involved have an established history of effective collaboration and will use their complementary expertise and resources to take a multi-disciplinary approach in the proposed research. Through the use of biochemical, cell biological, molecular, electrophysiological, structural and behavioral assays, the proposed Conte Center will achieve a fuller understanding of the cellular and molecular actions of antipsychotic drugs in the cortico-striatal circuits.

Public Health Relevance

Relevance to public health: Schizophrenia is a debilitating psychiatric disorder, and new therapies are needed. This Conte Center will characterize the effects of antipsychotic drugs on the properties of specific neuronal subtypes involved in schizophrenia, allowing for a complete understanding of the normal and maladaptive actions of these drugs, and leading to better therapies with higher efficacy and fewer side-effects.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Study Section
Special Emphasis Panel (ZMH1-ERB-M (02))
Program Officer
Nadler, Laurie S
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Rockefeller University
Other Domestic Higher Education
New York
United States
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Snyder, Gretchen L; Vanover, Kimberly E; Zhu, Hongwen et al. (2015) Functional profile of a novel modulator of serotonin, dopamine, and glutamate neurotransmission. Psychopharmacology (Berl) 232:605-21
Nakajima, Miho; Görlich, Andreas; Heintz, Nathaniel (2014) Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons. Cell 159:295-305
Dietz, David M; Kennedy, Pamela J; Sun, Haosheng et al. (2014) ýýFosB induction in prefrontal cortex by antipsychotic drugs is associated with negative behavioral outcomes. Neuropsychopharmacology 39:538-44
Svenningsson, P; Berg, L; Matthews, D et al. (2014) Preliminary evidence that early reduction in p11 levels in natural killer cells and monocytes predicts the likelihood of antidepressant response to chronic citalopram. Mol Psychiatry 19:962-4
Meyer, Douglas A; Torres-Altoro, Melissa I; Tan, Zhenjun et al. (2014) Ischemic stroke injury is mediated by aberrant Cdk5. J Neurosci 34:8259-67
Surmeier, D James; Graves, Steven M; Shen, Weixing (2014) Dopaminergic modulation of striatal networks in health and Parkinson's disease. Curr Opin Neurobiol 29:109-17
Heiman, Myriam; Kulicke, Ruth; Fenster, Robert J et al. (2014) Cell type-specific mRNA purification by translating ribosome affinity purification (TRAP). Nat Protoc 9:1282-91
Oh, Yong-Seok; Gao, Pu; Lee, Ko-Woon et al. (2013) SMARCA3, a chromatin-remodeling factor, is required for p11-dependent antidepressant action. Cell 152:831-43
Nestler, Eric J (2013) Treating the brain deep down: Brain surgery for anorexia nervosa? Nat Med 19:678-9
Svenningsson, Per; Kim, Yong; Warner-Schmidt, Jennifer et al. (2013) p11 and its role in depression and therapeutic responses to antidepressants. Nat Rev Neurosci 14:673-80

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