Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• 22q11.2 deletion syndrome (22q11.2DS) is linked to neurodevelopmental disorders, including schizophrenia and ADHD.
• Attentional impairment is a significant cognitive deficit in these disorders, necessitating effective interventions.
• Mouse models are crucial for understanding the neurobiological underpinnings of 22q11.2DS and testing therapeutic strategies.

Purpose of the Study:

• To assess attentional and executive function deficits in a 22q11.2DS mouse model using a touchscreen rodent continuous performance test (rCPT).
• To investigate the neurobiological correlates of cognitive dysfunction in this model, focusing on prefrontal cortical-hippocampal synchrony.
• To evaluate the efficacy of psychostimulants, specifically amphetamine and modafinil, in ameliorating attentional deficits.

Main Methods:

• Utilized the Df(h22q11)/+ mouse model, a genetic model for 22q11.2DS.
• Administered a touchscreen rodent continuous performance test (rCPT) to assess attention and executive function.
• Measured prefrontal cortical-hippocampal oscillatory synchrony during quiet wakefulness and assessed behavioral responses to amphetamine and modafinil.

Main Results:

• Df(h22q11)/+ male mice exhibited significantly impaired attentional performance (decreased hit rate and discrimination sensitivity) compared to wild-type littermates.
• Reduced prefrontal cortical-hippocampal oscillatory synchrony was observed in the Df(h22q11)/+ model, potentially serving as a biomarker for cognitive dysfunction.
• Amphetamine dose-dependently improved discrimination sensitivity in Df(h22q11)/+ mice, while modafinil exacerbated impairments at the highest dose.

Conclusions:

• This study provides the first direct evidence of attentional impairment in a 22q11.2DS mouse model, validating its relevance to human endophenotypes.
• The rCPT is a sensitive tool for detecting cognitive deficits and evaluating treatment efficacy in this model.
• The findings highlight the potential of psychostimulants like amphetamine for managing attentional deficits in 22q11.2DS, underscoring the translational value of the Df(h22q11)/+ model.