Schmack lab

Neural Circuits and Immunity in Psychosis Laboratory

: Neural circuits

We study neural circuit mechanisms of psychosis-like experiences to find new treatment targets for psychosis. We believe that progress in treating psychotic disorders will come together with fundamental insights into perception and thought.  

Psychosis involves excessive dopamine release in the striatum, and all available antipsychotic drugs block dopamine receptors. However, these antipsychotic drugs show limitations due to drug-induced dopamine receptor sensitization. We think that these limitations can be overcome by harnessing the brain’s endogenous mechanisms for modulating dopamine release rather than blocking dopamine receptors.

Therefore, we study striatal and extra-striatal neuron populations that act on dopamine release. We use a computational-behavioral approach to measure psychosis-like experiences in mice, and combine this with a range of neural manipulations such as optical imaging, optogenetics and pharmacology. The goal is to uncover the functional role of dopamine-modulating neuron populations in psychosis-like experiences. We then apply targeted transcriptomic profiling methods to find molecular markers of those neuron populations that are relevant to psychosis-like experiences. This will allow us to develop a new class of antipsychotic treatments that targets neural circuits upstream of dopamine receptors.