Dopamine (DA) signaling depends upon the coordination of multiple presynaptic processes, including those supporting DA biosynthesis, packaging, release and reuptake. The presynaptic dopamine transporter (DAT-1) is of particular importance in regulating both the exposure of pre- and postsynaptic DA receptors as well as supporting recycling of DA for further rounds of release. Using Caenorhabditis elegans, our lab demonstrated that loss of DAT (dat-1) elicits a DA-dependent, locomotory phenotype termed Swimming Induced Paralysis (SWIP) (Mcdonald et al., 2007). Whereas wild-type (N2) L4 stage worms swim at a continuous rate for ~20 min., dat-1 worms initiate normal swimming, but then paralyze over the next six minutes. SWIP can be rescued by pretreatment with the vesicular DA transporter (CAT-1) inhibitor reserpine, loss of DA biosynthesis (cat-2) or loss of the DA receptor DOP-3 (dop-3). In our initial studies, dat-1 SWIP was thought to be evident in either water or M9 buffer. Recently, however, we tested N2 and dat-1 worms for SWIP in both media, as well as three sucrose-supplemented water solutions. As shown in Fig. 1, as the osmolarity of the aqueous media increases, dat-1 SWIP penetrance decreases significantly. In contrast, swimming of wild-type worms is unaffected by media osmolarity. Although the effects of osmolarity on neural activity in worms have been well documented, here we show that media composition modulates a DA-modulated C. elegans motor behavior by DA and possibly other biogenic amines like serotonin. Candidate, reverse or forward genetic manipulations of SWIP in water vs. M9 may provide an opportunity to further dissect DA signaling in the nematode in vivo.
1Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 2Departments of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, 3Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN, 4Neuroscience Graduate Program, Vanderbilt University School of Medicine, Nashville, TN
Correspondence to: Randy D. Blakely (firstname.lastname@example.org)