F A C U L T Y   P R O F I L E 

Robert Kass

KELLENDONK, CHRISTOPH, PH.D.
Associate Professor of Pharmacology in Psychiatry

Neural mechanisms of cognition and motivation.

Office: NYSPI | Annex 3rd floor| Room 355
Telephone: 646.774.8602
Email:
ck491@columbia.edu

Kellendonk Lab

Current 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


 

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 (7):987-996

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.