Eleanor Simpson, PhD
- Assistant Professor of Clinical Neurobiology (in Psychiatry)
Eleanor H. Simpson obtained a BSc in Biological Sciences from the University of Lancaster UK including a year of study at the University of California at Irvine. She then obtained a PhD from the University of Edinburgh, UK. Her graduate research, funded by the MRC, was focused on developmental genetics using mouse models. Dr. Simpson did her postdoctoral training in the laboratory of Prof. Eric Kandel, supported by the Howard Hughes Medical Institute. During this training she developed transgenic mouse models of dopamine dysfunction that are based on molecular alterations that have been observed in patients with psychiatric disorders.
Dr. Simpson is currently a Research Scientist VI at the New York State Psychiatric institute, and an Assistant Professor of Clinical Neurobiology in Psychiatry. The overall goal of her research is to improve our understanding of the neurobiological basis of symptoms suffered by patients with psychiatric disorders so that potential treatment targets may be identified. The types of symptoms that she models in mice include the deficits in cognition that are suffered by patients with schizophrenia and the deficits in motivation that occur in schizophrenia as well as affective disorders. Dr. Simpson's research is supported by the NIH. She is an Investigator in the NIMH-funded Silvio O. Conte Center at NYSPI, a basic and translational research center focused on dopamine dysfunction in schizophrenia. Further information about this center is available at: http://schizophrenia.conte.cumc.columbia.edu/
Credentials & Experience
Education & Training
- PhD, Genetics, University of Edinburgh (United Kingdom)
The goal of my research is to understand the neurobiological basis of the behavioural processes that are disrupted in psychiatric disorders. Specifically we focus on the role of the dopamine system in cognition and motivation.
My research program is focused on the role of the dopamine system in cognitive and behavioural processes that are disrupted in patients with psychiatric disorders. We use laboratory mice and introduce genetic, viral vector mediated, pharmacological or pharmacogenetic perturbations to probe the dopamine system in vivo. Some of these manipulations are based on molecular alterations that have been observed in patients with psychiatric disorders. For example, we use a transgenic mouse model of the increase in dopamine D2 receptor signaling in the striatum that occurs in patients with schizophrenia to examine the potential pathophysiological cascades that may lead to disease. This mouse model displays behavioral abnormalities highly relevant to schizophrenia. These include deficits in working memory and cognitive flexibility, distinctive features of the cognitive symptoms of the disease. The mice also display deficits in incentive motivation, a core component of the negative symptoms. These symptoms represent major barriers to patient's functional outcome and quality of life. As well as studying these behaviours in my own mouse models, I am also devoted to improving the behavioural assays available to other translational researchers in order to permit more meaningful comparisons between animal models and patient symptoms.
In addition to performing behavioural analysis in our mouse models, to better understand the role of neuromodulatory mechanisms in behavioural processes, my lab also employs methods for detecting dopamine signaling during behavior. We use in vivo microdialysis to measure tonic changes in extracellular dopamine tone while animals are working to earn rewards. We also use in vivo Fast Scan Cyclic Voltammetry (FSCV) to quantify phasic dopamine release events while animals are learning to perform cognitive tasks. We use these in vivo methods to investigate potential pathogenic changes in the dopamine system that may give rise to psychiatric symptoms, and also to explore pharmacological agents that modulate the dopamine system and may be useful candidates for novel treatments.
Ward RD, Winiger V, Kandel ER, Balsam PD, Simpson EH.:Orbitofrontal cortex mediates the differential impact of signaled-reward probability on discrimination accuracy. Front Neurosci. 2015 Jun 23;9:230.
Krabbe S, Duda J, Schiemann J, Poetschke C, Schneider G, Kandel ER, Liss B, Roeper J, Simpson EH.:Increased dopamine D2 receptor activity in the striatum alters the firing pattern of dopamine neurons in the ventral tegmental area. Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):E1498-506
Simpson EH, Kellendonk C, Ward RD, Richards V, Lipatova O, Fairhurst S, Kandel ER, Balsam PD.: Pharmacologic rescue of motivational deficit in an animal model of the negative symptoms of schizophrenia. Biol Psychiatry 2011;69(10): 928-35
Simpson EH, Kellendonk C, Kandel ER.: A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron 2010;65(5): 585-96
Kellendonk C, Simpson EH, Polan HJ, Malleret G, Vronskaya S, Winiger V, Moore H, Kandel ER.: Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 2006;49(4): 603-15