New Modes of GPCR Signalling

Inhibitory Effect of Ethanol on Gustatory Plasticity in C. Elegans
Mediated by the Serotonin Pathway
Ying Wang, Lichun Tang, Wei Du, Bi-Feng Liu*
Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for
Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory,
Department of Systems Biology, College of Life Science and Technology, Huazhong
University of Science and Technology, Wuhan 430074, People’s Republic of China.
Aim Ethanol can affect the formation of learning and memory in many species.
However, the molecular mechanisms underlying the behavioral effects of ethanol are
still poorly understood. The results from the invertebrate model organisms contribute to
and accelerate the research in higher animal species. So the effect of acute ethanol
exposure on learning and memory in invertebrates yet needs to be studied more in-depth.
Methods In C. elegans, gustatory plasticity is a simple learning paradigm, in which
animals after prolonged pre-exposure to a chemo-attractive salt show chemo-aversion to
this salt. We are using this learning model to study the effect of ethanol on learning and
memory in C. elegans. Results Our results show that ethanol exhibits an acute
inhibitory effect on gustatory plasticity in well-fed C. elegans. Genetic analysis revealed
that mutant animals with defects in serotonin synthetic enzyme tph-1 failed to exhibit
ethanol’s inhibitory effect on gustatory plasticity, however this inhibitory effect could
be restored by expression of tph-1 in the NSM neurons. In addition, tph-1 acts as a
partial downstream target of the BK potassium channel slo-1, regulating acute
intoxicating effects of ethanol in locomotion and egg-laying. Furthermore, we show that
G protein-coupled receptors of serotonin SER-4, SER-7 as well as G-protein α subunits
GPA-3, GPA-11 possibly function in the same genetic pathway to modulate this
response to ethanol. Results of calcium imaging indicate that ethanol directly changes
the activity of ASER neuron that plays a dominant role in chemotaxis to salt.
Conclusion Together, our results demonstrate the distinct role of serotonin pathway in
modulation of acute response to ethanol in gustatory plasticity in C. elegans. Also, the
effect of ethanol on gustatory plasticity explored in our study is a novel example of the
effect of ethanol on learning behavior.
Key Words: Caenorhabditis elegans, ethanol, gustatory plasticity, serotonin pathway
*Corresponding author
Tel: 86-27-87792203 , Email: bfliu@mail.hust.edu.cn