Researchers at Florida Atlantic University are utilizing the transparent worm Caenorhabditis elegans to study dopamine signaling, leveraging its genetic similarities to humans for more efficient research compared to rodent models.

Dopamine is a key neurotransmitter that plays a crucial role in regulating attention, pleasure, reward, and movement coordination.

Altered dopamine signaling is associated with various brain disorders, including substance use disorder, ADHD, autism, bipolar disorder, schizophrenia, and Parkinson's disease.

The Million Mutation Project (MMP) has provided access to a collection of 2,007 C. elegans strains, each with chemically induced gene mutations, facilitating rapid identification of mutant genes.

Using the MMP approach, researchers screened over 23,000 mutations and identified 10 strains related to dopamine-dependent Swimming-induced-paralysis (Swip) behavior.

The research team tested 300 MMP lines to identify worms exhibiting Swip behavior, confirming that excess dopamine signaling was the underlying cause.

Loss of the BBS-1 gene in C. elegans leads to excessive dopamine signaling, which inhibits movement-controlling neurons, suggesting its role in maintaining dopamine levels.

Further screening revealed mutations linked to Bardet-Biedl Syndrome (BBS), a rare genetic disorder affecting multiple proteins in a complex known as the BBSome.

The BBSome complex is crucial for transporting proteins and lipids within cells and is involved in dopamine neuron signaling in C. elegans.

Randy D. Blakely, Ph.D., leads the research, emphasizing that C. elegans allows for faster genetic analysis compared to rodent models due to the evolutionary conservation of dopamine regulation proteins.

Initial findings included novel mutations in the dat-1 gene, responsible for dopamine reuptake in worms, confirming the efficacy of their screening approach.

The MMP library contains over 800,000 unique genetic changes, facilitating the study of gene disruption's effects on physiology and behavior.