Eleanor Simpson, PhD
- Assistant Professor of Clinical Neurobiology (in Psychiatry)
Eleanor H. Simpson obtained a PhD in Genetics from the University of Edinburgh, UK and completed her postdoctoral training with Prof. Eric Kandel. During this training she developed transgenic mouse models of dopamine dysfunction, each based on molecular alterations observed in patients with psychiatric disorders. Dr. Simpson is currently a Research Scientist VI at NYSPI, and an Assistant Professor of Clinical Neurobiology in Psychiatry at Columbia University. The overall goal of her research is to understand how dysfunction of neuromodulatory systems mediates the cognitive and negative symptoms of schizophrenia.
Dr. Simpson’s laboratory uses transgenic, viral and chemogenetic manipulations in mice to test hypothesis-driven ideas about neurobiological mechanisms underlying behavior. The effects of selective manipulations are studied using in vivo techniques including microdialysis and Fast Scan Cyclic Voltammetry (FSCV) to monitor dopamine signaling across different timescales. The lab also performs in vivo fiber photometry of fluorescent calcium indicators to monitor neural activity (somatic and terminal) in genetically identified dopamine neurons.
Working closely with the experimental psychologist Prof. Peter Balsam, together they have developed novel tasks and quantitative approaches to isolate highly specific behavioral processes (e.g. sensitivity to reward value), representing components of broader psychological constructs (e.g. motivation). Combining such precise behavioral analysis with multiple in vivo methods allows for a more discrete mapping of molecular, cellular and circuit mechanisms onto behavioral processes.
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