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Social cognition in 22qll.2 schizophrenia mouse model - role of mPFC dysfunction and oxytocin

Schizophrenia is associated with impairment of social cognition and social function. Medial prefrontal cortex (mPFC) is crucial for processing of social cues and regulation of social behaviour. Altered connectivity within mPFC in schizophrenia patients compared to healthy controls could explain patients’ poorer ability to differentiate between individuals and impairment to emotion recognition. 22q11.2 deletion syndrome is one of the largest know genetic risk factors for developing schizophrenia and is associated with impairments to social recognition and emotion processing. However, the changes to mPFC neurocircuitry in 22q.11.2 causing the social cognition deficits remain poorly understood. Oxytocin (OXT) is pivotal to social recognition and social function. Inactivation of mPFC OXT receptors impairs social recognition in mice comparable to social cognition deficits in schizophrenia. The 22q11.2 deletion mouse model (LgDel) displays impairments to social memory and emotion recognition and mice display altered mPFC neuronal activity patterns during cognitive tests and brain OXT levels are lower in LgDel compared to wild type mice. These findings suggest that social cognitive deficits in schizophrenia could be caused by disruption to mPFC neurocircuitry, possibly mediated by altered OXT availability or by OXT modulation of dopamine within mPFC. Using a combination of cutting edge electrophysiological recordings and measurement of OXT and dopamine real-time dynamics during a battery of non-social and social cognitive tests, I aim to deliver detailed information about neuronal activity and synchrony throughout the mPFC in during social cognition tests in WT and LgDel mice. This will provide insight into the micro-circuitry underlying changes to neurofunction and cognition in schizophrenia cause impairments, which could aid the improvement of treatment of social cognition deficits in Schizophrenia.

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Christine Stubbendorf
Christine Stubbendorf
Genetics of Cognition
Total budget: 172.750,08€
Total contribution: 172.750,08€