BackgroundPrecise 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 Gαi subunit (GPA-14) in the anterior deirid (ADE) pair of dopaminergic neurons.FindingsIn 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.ConclusionOur 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 Gαi 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.

is given to submissions in areas of synaptic and neuronal electrophysiology, studies of ion channel and transporter biophysics, computational neuroscience, single synapse imaging and optogenetics, sensory systems, and developmental neurobiology. Cover Caption: The cover image is based on the Short Communication Synaptic vesicle fusion is modulated through feedback inhibition by dopamine auto-receptors by Rosaria Formisano et al., Research Articles e22128 Opioid modulation of cochlear auditory responses in the rat inner earTeresa Ramírez, Enrique Soto, and Rosario Vega e22130 Sexually dimorphic responses of rats to fluoxetine in the forced swimming test are unrelated to the function of the serotonin transporter in the brain

Modulatory mechanisms of neurotransmitter release and clearance are highly controlled processes whose finely tuned regulation is critical for functioning of the nervous system. Dysregulation of the monoamine neurotransmitter dopamine can lead to several neuropathies. Synaptic modulation of dopamine is known to involve pre‐synaptic D2 auto‐receptors and acid sensing ion channels. In addition, the dopamine membrane transporter (DAT), which is responsible for clearance of dopamine from the synaptic cleft, is suspected to play an active role in modulating release of dopamine. Using functional imaging on the Caenorhabditis elegans model system, we show that DAT‐1 acts as a negative feedback modulator to neurotransmitter vesicle fusion. Results from our fluorescence recovery after photo‐bleaching (FRAP) based experiments were followed up with and reaffirmed using swimming‐induced paralysis behavioral assays. Utilizing our numerical FRAP data we have developed a mechanistic model to dissect the dynamics of synaptic vesicle fusion, and compare the feedback effects of DAT‐1 with the dopamine auto‐receptor. Our experimental results and the mechanistic model are of potential broader significance, as similar dynamics are likely to be used by other synaptic modulators including membrane transporters for other neurotransmitters across species.

The cover image is based on the Short Communication Synaptic vesicle fusion is modulated through feedback inhibition by dopamine auto‐receptors by Rosaria Formisano et al., DOI .