Christoph Kellendonk, PhD

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Overview

Academic Appointments

  • Associate Professor of Pharmacology in Psychiatry

Dr. Kellendonk obtained his PhD in the laboratory of Günther Schütz at the German Cancer Research Center in Heidelberg where he studied the function of the glucocorticoid receptor. He then joined Eric Kandel's laboratory at Columbia University in New York as a post-doctoral research fellow where he became interested in using mouse genetics to study neuropsychiatric disorders. Since 2008 Dr. Kellendonk is an independent investigator in the Departments of Pharmacology and Psychiatry at Columbia University. 

Gender

  • Male

Research

The Kellendonk laboratory uses mouse genetic tools in an effort to understand the biology that underlies cognitive and negative symptoms of schizophrenia. Schizophrenia is characterized by three symptom clusters: the cognitive, negative and positive symptoms. While the positive symptoms – which include disordered thought processes, hallucinations and delusions – are the most characteristic feature of the disorder, such symptoms are more difficult to model in the mouse. In contrast, cognitive and negative symptoms of the disorder – including deficits in working memory and motivation – have behavioral readouts in mice that are more homologous to humans. Cognitive and negative symptoms are poorly understood, difficult to treat and their severities are a better predictor for the long-term prognosis of patients than the degree of positive symptoms.

Our approach uses observations made in patients with schizophrenia (e.g. with brain imaging) and then seeks to “model” these observations as closely as possible in the mouse. This allows for establishing causality between a specific brain alteration and changes in behavior. Using this approach we hope to achieve three main goals:

1)         To better understand the basic neuronal mechanisms that support cognitive and motivated behaviors

2)         To inspire new studies in humans based on observations made in the mouse

3)         To identify new treatment strategies for enhancing cognition and motivation

Research Interests

  • Neurobiology of Learning and Memory
  • Neurogenetics
  • Models of Psychiatric Disorders
  • Neurobiology of Disease

Grants

THE EFFECT OF ADOLESCENT THALAMIC INHIBITION ON ADULT PREFRONTAL CORTICAL FUNCTION (Federal Gov)

Jul 1 2019 - Jun 30 2023

TARGETING COTRANSMISSION FOR CIRCUIT-SPECIFIC PHARMACOTHERAPY (Federal Gov)

Sep 1 2018 - May 31 2023

IDENTIFYING NEURONAL CIRCUITS AND MECHANISMS OF WORKING MEMORY (Private)

Jan 1 2013 - Dec 31 2018

THE ROLE OF THALAMIC DOPAMINE D2 RECEPTORS IN COCAINE INTAKE (Federal Gov)

Jul 1 2017 - Jun 30 2018

PLASTICITY OF BRIDGE COLLATERALS IN PARKINONIAN STATE AND TREATMENT (Federal Gov)

May 15 2016 - Mar 31 2018

TO STUDY THE EFFECTS OF THE DOPAMINE D2/D3 PARTIAL AGONIST ANTIPSYCHOTIC CARIPRAZINE ON MOTIVATION IN MICE OVEREXPRESSING D3 RECEPTORS (Private)

Apr 26 2016 - Apr 25 2017

FUNCTIONALLY SELECTIVE D2R S, STRIATAL CIRCUIT FUNCTION AND MOTIVATION (Federal Gov)

May 20 2016 - Mar 31 2017

MEDIUM SPINY NEURON EXCITABILITY AND MOTIVATION (Federal Gov)

May 20 2011 - Sep 30 2016

OPTOGENETIC DISSECTION OF THALAMOPREFRONTAL CIRCUITRY SUPPORTING SPATIAL WORKING MEMORY (Federal Gov)

Jul 1 2014 - Jun 30 2016

FUNCTIONAL CONNECTOME ANALYSIS OF AMPHETAMINE ACTION AT DOPAMINE NEURON SYNAPSES (Federal Gov)

Feb 1 2015 - Feb 29 2016

THE FUNCTION OF MEDIO-DORSAL ACTIVITY DURING ADOLESCENCE IN CORTICAL MATURATION (Private)

Jan 15 2013 - Jan 14 2015

FURTHER BEHAVIORAL STUDIES IN DOPAMINE RECEPTOR OVER-EXPRESSING MICE (Private)

Jan 8 2013 - Dec 31 2014

PROFILING OF CARIPRAZINE AND COMPARATORS IN ANIMAL MODELS OF MOTIVATION (NEGATIVE SYMPTOMS (Private)

Nov 15 2013 - Dec 1 2014

THE FUNCTION OF THE THALAMO-FRONTOCORTICAL PROJECTIONS IN CO GNITION IN THE MOUSE (Private)

Jul 1 2009 - Jun 30 2011

Selected Publications

  1. Bolkan S., Stujenske J.M., Parnaudeau S., Spellman T.J, Rauffenbart C., Abbas A., Harris A.Z., Gordon J.A., Kellendonk C. (2017) Thalamic projections sustain prefrontal activity during working memory maintenance Nature Neuroscience doi:10.1038/nn.4568
  2. Carvalho Poyraz F., Holzner E., Bailey M.R., Meszaros J., Kenney L., Kheirbek M.A., Balsam P.D., Kellendonk C. (2016) Decreasing striato-pallidal pathway function enhances motivation by energizing the initiation of goal directed action J. Neuroscience 36(22):5988-6001
  3. Canetta S., Bolkan S., Padilla-Coreano N., Song L.J., Sahn R., Harrison N.L., Gordon J.A., Brown A., Kellendonk C. (2016) Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons. Molecular Psychiatry 21(7):956-68
  4. Gallo E.F., Salling M.C., Feng B., Morón J.A., Harrison N.L., Javitch J.A., Kellendonk C. (2015) Upregulation of dopamine D2 receptors in the nucleus accumbens indirect pathway increases locomotion but does not reduce alcohol consumption. Neuropsychopharmacology 40:1609-18.
  5. Parnaudeau S, Taylor K, Bolkan SS, Ward RD, Balsam PD, Kellendonk C. (2015) Mediodorsal thalamus hypofunctionimpairs flexible goal-directed behavior. Biological Psychiatry. 77:445-453.
  6. Cazorla M, de Carvalho FD, Chohan MO, Shegda M, Chuhma N, Rayport S, Ahmari SE, Moore H, Kellendonk C. (2014) Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry. Neuron. 81:153-164.
  7. Parnaudeau S, O'Neill PK, Bolkan SS, Ward RD, Abbas AI, Roth BL, Balsam PD, Gordon JA, Kellendonk C. (2013) Inhibition of mediodorsal thalamus disrupts thalamofrontal connectivity and cognition. Neuron. 77:1151-1162.
  8. Cazorla M, Shegda M, Ramesh B, Harrison NL, Kellendonk C. (2012) Striatal D2 receptors regulate dendritic morphology of medium spiny neurons via Kir2 channels. J Neuroscience. 32:2398-2409.