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Studying Schizophrenia in a Dish: Use of Primary Neuronal Cultures to Study the Long-Term Effects of NMDA Receptor Antagonists on Parvalbumin-Positive Fast-Spiking Interneurons

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Animal Models of Schizophrenia and Related Disorders

Part of the book series: Neuromethods ((NM,volume 59))

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Abstract

Evidence obtained from schizophrenia post-mortem brain studies have pointed to deficiencies in inhibitory systems, in particular of the fast-spiking parvalbumin (PV)-positive inhibitory interneurons, as responsible for several aspects of schizophrenia pathophysiology. This hypothesis has been confirmed in pharmacological as well as genetic models of the disease, but when and how this dysfunction occurs is still unknown. Exposure to NMDA receptor antagonists is one of the most used pharmacological models for the study of schizophrenia, due to its capacity to produce a psychotic syndrome in humans and to produce an outbreak in schizophrenia patients. Using this model, we and others have shown that dysfunction of the PV-inhibitory system is most probably responsible for the neural network alterations, leading to the schizophrenia-like behavior in primates and rodents. Development of PV-inhibitory neurons occurs postnatally in mammals and follows a predetermined program that occurs also in cultures of cortical neurons. In this chapter we describe in detail the methodology we have used over the last decade to culture these neurons and that led to the discovery of how blockade of NMDA receptors results in the dysfunction of PV interneurons.

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Authors and Affiliations

  1. The Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA

    M. Margarita Behrens

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Correspondence to M. Margarita Behrens .

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  1. School of Medicine, Depts. of Anatomy & Neurobiology, University of Maryland, Penn St. 20, Baltimore, 21201, Maryland, USA

    Patricio O'Donnell

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Behrens, M.M. (2011). Studying Schizophrenia in a Dish: Use of Primary Neuronal Cultures to Study the Long-Term Effects of NMDA Receptor Antagonists on Parvalbumin-Positive Fast-Spiking Interneurons. In: O'Donnell, P. (eds) Animal Models of Schizophrenia and Related Disorders. Neuromethods, vol 59. Humana Press. https://doi.org/10.1007/978-1-61779-157-4_6

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  • DOI: https://doi.org/10.1007/978-1-61779-157-4_6

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