Identification of the specific role of the D2-like dopamine receptor DOP-2

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Dopamine signaling plays important roles in many neuronal activities. Dysfunction of the dopaminergic system is thought to be associated with several mental and neurological disorders, such as Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder (ADHD) and drug addition (Ford, 2014). Dopaminergic signaling is highly conserved across the species. In the nematode C.elegans, the dopaminergic system controls a variety of behaviors, including locomotion, foraging and learning (Voglis & Tavernarakis, 2008). In this study, the Caenorhabditis elegans model was used to understand the auto-receptor functional component of the DOP-2 receptor in modulating dopamine levels in the synaptic cleft. In C. elegans, the D2-like dopamine receptor DOP-2 is expressed in all eight of its dopaminergic neurons; it might act as an auto-receptor that modulates dopamine levels at synapses in the nematode. In order to investigate the possible role of DOP-2 as a regulator of dopamine release in the dopamine signaling that takes place at synapses in C. elegans, this study focused on analyzing synaptic vesicle release in dop-2 mutants in vivo using FRAP (Fluorescence Recovery After Photobleaching). Results for FRAP experiments showed that dop-2 deficiency impairs synaptic activity in these worms by increasing the level of dopamine release required for normal dopamine activity in the nematode. In parallel, both behavioral and molecular studies were also used to test for the functional contribution of DOP-2 in the dopamine modulatory mechanism. Using a well-known behavioral assay, the SWimming Induced Paralysis (SWIP), a phenotype which is regulated by exogenous dopamine, it was confirmed that dop-2 is important to regulate dopamine release. The expression pattern of dop-2 was also analyzed in this study. dop-2 expression was observed in both cell bodies and processes of the head dopaminergic neurons CEP and ADE. On the basis of all these observations, we can conclude that the DOP-2 auto-receptor influences dopamine activity in C. elegans.

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