Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Khokhar, Jibran Y.

Abstract

CADM2 is a synaptic adhesion molecule associated with cognition and impulsivity. It is primarily expressed in the brain, especially in regions involved in executive function, addiction, motivation, and impulsivity control. Previous genetic studies have associated the CADM2 gene with different attentional and impulsivity traits. Continuous Performance Tests (CPT) are used to assess deficits in attentional function and impulse control in humans. This test has been used to study these deficits in different neuropsychiatric disorders such as ADHD. In the current study, we conducted the rodent version of CPT (rCPT) using touchscreen chambers. Our cohort of wildtype, heterozygous and knock-out Cadm2 mice were run on rCPT and a Progressive Ratio task to investigate how the impulsive and motivation related behaviours of these animals may differ. We discovered that Cadm2 genetic variation resulted in differences in these traits, with knock-out animals showing different outcomes compared to the wildtype and heterozygous mice.

Summary for Lay Audience

This study investigates how CADM2, a gene, might influence behaviours linked to impulsivity and motivation. Impulsivity, a personality trait involving acting without thinking, and the inability to withhold actions, is known to be partly heritable. Impulsivity is often seen in people with psychiatric conditions such as Attention-Deficit/Hyperactivity Disorder (ADHD) and/or substance use disorders. Similarly, aspects of motivation are also partly heritable and can impact the way individuals experience rewards and may influence the likelihood of substance us and psychiatric conditions. Previous research, specifically looking at the relationship between different traits and human genetics, has linked CADM2to impulsivity and motivation-related traits, but the exact mechanisms are unclear. To investigate how these traits may be influenced by this gene, we used a genetically modified mouse model lacking the Cadm2 gene. We used a touchscreen chamber designed for mice and observed their behaviour in two different tasks. The first task, called rodent Continuous Performance Task (rCPT), measures attention and impulsivity. The second task, called Progressive Ratio, measures how much effort a mouse is willing to put in for a food reward. These results of our study showed that the mice completely lacking the Cadm2 gene behaved differently from the mice with one or both copies of this gene, demonstrating the importance of CADM2 in these traits. These findings may improve our understanding of impulsivity, motivation, and related psychiatric conditions such as ADHD.

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