Research Goals

The Kellendonk laboratory uses mouse genetic tools in an effort to understand the biology that underlies symptoms of schizophrenia. Schizophrenia is characterized by three symptom clusters: the cognitive, negative and positive symptoms. The positive symptoms – which include disordered thought processes, hallucinations and delusions – are the most characteristic feature of the disorder. Positive symptoms are difficult to model in the mouse, although recent evidence suggest that Bayesian models of hallucinations may be a way of studying neuronal mechanisms of hallucinations in animals. The cognitive and negative symptoms of the disorder – including deficits in working memory and motivation – are central to the disorder as they are a better predictor for the long-term prognosis of patients than the degree of positive symptoms. Studying the neuronal mechanism underlying cognitive and motivated behaviors may lead to new therapeutic strategies to treat cognitive and negative 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 neuronal mechanisms that support cognitive and motivated behaviors

2) To better understand neuronal mechanisms that support hallucinations

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