Department of Biological Sciences, Delaware State University, Dover, DE 19901, USA.
Behav Brain Funct. 2013 Apr 22;9:16. doi: 10.1186/1744-9081-9-16.
Precise levels of specific neurotransmitters are required for appropriate neuronal functioning. The neurotransmitter dopamine is implicated in modulating behaviors, such as cognition, reward and memory. In the nematode Caenorhabditis elegans, the release of dopamine during behavioral plasticity is in part modulated through an acid-sensing ion channel expressed in its eight dopaminergic neurons. A D2-like C. elegans dopamine receptor DOP-2 co-expresses along with a Gα(i) subunit (GPA-14) in the anterior deirid (ADE) pair of dopaminergic neurons.
In follow-up experiments to our recently reported in vitro physical interaction between DOP-2 and GPA-14, we have behaviorally characterized worms carrying deletion mutations in gpa-14 and/or dop-2. We found both mutants to display behavioral abnormalities in habituation as well as associative learning, and exogenous supply of dopamine was able to revert the observed behavioral deficits. The behavioral phenotypes of dop-2 and gpa-14 loss-of-function mutants were found to be remarkably similar, and we did not observe any cumulative defects in their double mutants.
Our results provide genetic and phenotypic support to our earlier in vitro results where we had shown that the DOP-2 dopamine receptor and the GPA-14 Gα(i) subunit physically interact with each other. Results from behavioral experiments presented here together with our previous in-vitro work suggests that the DOP-2 functions as a dopamine auto-receptor to modulate two types of learning, anterior touch habituation and chemosensory associative conditioning, through a G-protein complex that comprises GPA-14 as its Gα subunit.
适当的神经元功能需要特定神经递质的精确水平。神经递质多巴胺被认为可以调节行为，如认知、奖励和记忆。在秀丽隐杆线虫中，行为可塑性期间多巴胺的释放部分通过其八个多巴胺能神经元中表达的酸感应离子通道来调节。类似于 D2 的秀丽隐杆线虫多巴胺受体 DOP-2 与 Gα(i)亚基（GPA-14）一起在前感觉神经元（ADE）对多巴胺能神经元中表达。
在我们最近报道的 DOP-2 和 GPA-14 之间体外物理相互作用的后续实验中，我们对携带 gpa-14 和/或 dop-2 缺失突变的蠕虫进行了行为特征分析。我们发现这两种突变体在习惯化和联想学习中都表现出行为异常，并且外源性供应多巴胺能够逆转观察到的行为缺陷。dop-2 和 gpa-14 功能丧失突变体的行为表型非常相似，我们没有观察到它们的双突变体中存在任何累积缺陷。
我们的结果为我们之前的体外结果提供了遗传和表型支持，我们之前的体外结果表明 DOP-2 多巴胺受体和 GPA-14 Gα(i)亚基相互物理作用。这里呈现的行为实验结果以及我们之前的体外工作表明，DOP-2 作为多巴胺自受体发挥作用，通过包含 GPA-14 作为其 Gα 亚基的 G 蛋白复合物来调节两种类型的学习，即前触习惯化和化学感觉联想条件作用。
