Adhesion GPCR latrophillin - 3 modulation of dopaminergic neurotransmission
Supervisors:
Dr Nicole Perry-Hauser, School of Molecular Biosciences
Dr Mick Craig, School of Psychology & Neuroscience
Prof Andrew Tobin, School of Molecular Biosciences
Summary:
Normal dopamine signaling is essential for basic functions like motor control, motivation, and working memory, and disruptions in this signaling are linked to various nervous system disorders. The adhesion G protein-coupled receptor latrophilin-3 (ADGRL3) gene is associated with dopamine signaling, and genetic variations in ADGRL3 are implicated in a higher risk of attention-deficit/hyperactivity disorder (ADHD) and substance use disorder. In animal studies, ADGRL3 disruption has been shown to alter dopaminergic neurotransmission, although the exact mechanisms remain unclear. This suggests ADGRL3 as a promising therapeutic target for disorders involving dopamine dysfunction.
This PhD project offers the opportunity to gain expertise in innovative techniques, including genetic manipulation, high-resolution imaging, rodent behavioral assays, and in vivo fiber photometry. Using a floxed ADGRL3 mouse line, the student will help create tissue-specific deletions in dopaminergic neurons to explore how ADGRL3 modulates dopamine signaling in the striatum. The project will focus on three key objectives: determining whether ADGRL3 acts pre- or post-synaptically, characterizing the structural impact of ADGRL3 knockout on dopamine release sites, and investigating the role of ADGRL3 in motivation and impulsivity through behavioral testing coupled to fiber photometry recordings.