LgDel-mPFC · Social cognition in 22qll.2 schizophrenia mouse model – role of mPFC dysfunction and oxytocin
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-03-01 → 2025-02-28
- EU contribution
- €188,590
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Social cognition in 22qll.2 schizophrenia mouse model – role of mPFC dysfunction and oxytocin
Schizophrenia is a severe and disabling mental health disorder significantly impacting individuals' social interactions, including difficulties in recognizing others, interpreting emotions, and responding to social cues. These impairments considerably affect patients' quality of life, social integration, and the wellbeing of their families. The medial prefrontal cortex (mPFC) is a critical brain region involved in social cognition and emotion regulation. Dysfunction within this area is implicated in the social cognitive deficits characteristic of schizophrenia. This project aimed to clarify how alterations in the mPFC contribute to social cognition deficits in schizophrenia using a mouse model carrying a genetic mutation (22q11.2 deletion syndrome) strongly linked to schizophrenia. The 22q11.2 deletion mouse model, known as LgDel, exhibits social and cognitive impairments analogous to those seen in human patients, making it an ideal subject for understanding schizophrenia-associated brain changes. Specifically, the project aimed to: Map neuronal activity and communication patterns in the mPFC during social and cognitive tasks. Investigate fluctuations of oxytocin, a hormone crucial for social behaviors, within the mPFC during behavior. Examine how oxytocin interacts with dopamine—another critical neurotransmitter involved in social cognition—to influence social behaviors. This ambitious initiative utilized cutting-edge neuroscience technologies, including chronically implantable SiNAPS electrophysiological probes and fiber photometry to track real-time neurotransmitter fluctuations. Insights from this research have significant potential for improving treatments for schizophrenia and enhancing understanding of gender differences in the disorder.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA · GenovaCoordinatorItaly
Links
- View on CORDIS
- DOI: 10.3030/101066405
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e500c6fcb8&appId=PPGMS
Data: CORDIS, © European Union