Altered striatal dopamine regulation in ADGRL3 knockout mice

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Dopaminergic signaling is crucial for motor control, learning, and reward, with dysregulation implicated in ADHD.
• ADGRL3, a G protein-coupled receptor abundant in the brain, is genetically linked to ADHD.
• Previous studies show ADGRL3 deficiency impacts dopaminergic markers and behavior, but its precise role in dopamine modulation is unknown.

Purpose of the Study:

• To investigate the effect of ADGRL3 knockout on striatal dopamine release in mice.
• To elucidate the mechanisms by which ADGRL3 influences dopaminergic neurotransmission.

Main Methods:

• Utilized ex vivo fast-scan cyclic voltammetry to measure electrically-evoked dopamine release in striatal slices.
• Employed in vivo fiber photometry with a dopamine sensor to record dopamine dynamics during behavioral tasks.
• Administered amphetamine to assess dopamine release independent of task performance.

Main Results:

• Ex vivo experiments revealed enhanced electrically-evoked dopamine release in the striatum of ADGRL3 knockout mice.
• In vivo recordings showed diminished dopamine signals in the nucleus accumbens during an operant fixed interval task.
• Amphetamine-induced dopamine release remained unaltered, indicating dopamine availability was not globally impaired.

Conclusions:

• ADGRL3 plays a complex role in regulating dopamine release, affecting both presynaptic and postsynaptic mechanisms.
• The findings highlight ADGRL3 as a potential modulator of dopamine signaling relevant to ADHD pathophysiology.
• Further research is needed to fully delineate the intricate mechanisms of ADGRL3 in dopaminergic modulation.