Christoph Kellendonk

Christoph Kellendonk

Department of Psychiatry, Department of Pharmacology, Columbia University, New York
New York State Psychiatric Institute

Impaired motivation has been a long recognized negative symptom of schizophrenia, as well as a common feature of non-psychotic psychiatric disorders. It is responsible for a significant share of functional burden, also because treatment options are limited. Pharmacological studies have demonstrated an important role of dopamine D2 receptors in the ventral striatum in regulating motivated behaviors. However, D2 receptors are expressed in different neuronal cell types within the striatum including indirect pathway projection neurons, cholinergic interneurons and terminals from cortical and dopaminergic neurons. Expression in these different cell types complicates the interpretation of pharmacological manipulations. To dissect the function of D2 receptors in distinct striatal cell types we used genetic tools in the mouse and selectively overexpressed D2 receptors in either indirect pathway projection neurons or cholinergic interneurons of the Nucleus accumbens core.

During my presentation I will show evidence that D2Rs in both cell types of the ventral striatum regulate distinct motivated behaviors via different neuronal mechanisms. Understanding the mechanisms that regulate motivated behavior should in the long-term enable the development of new treatment strategies towards treating deficits in motivation.