Dopamine is a neurotransmitter in 8 cells in C. elegans, the sensory neurons ADEL/R, PDEL/R, CEPDL/R and CEPVL/R. Function of the dopaminergic neurons can be altered by mutations in
cat-2 , the gene for the dopamine synthetic enzyme tyrosine hydroxylase (Lints and Emmons, 1999).
cat-2 mutants show specific deficits in movement in viscous media; ablations of specific dopamine-containing neurons cause similar deficits (Sawin et al., 2000). Another protein that is important for the function of dopaminergic neurons is the vesicular monoamine transporter, VMAT. VMAT is responsible for loading synaptic vesicles with dopamine (or other monoamines) and is found in the dopamine-containing cells (as well as other aminergic neurons). Deletion of
cat-1 , the gene that encodes VMAT, leads to a variety of behavioral abnormalities, including defects in locomotion that are indicative of a loss of dopaminergic function (Duerr et al., 1999). Recently, we have begun to examine the function of another protein important for normal dopaminergic neurotransmission, the plasma membrane transporter for dopamine, DAT-1 (Jayanthi et al., 1998). In vertebrates, the dopamine transporter allows rapid re-uptake of released dopamine; interference with this transporter leads to increased concentrations of synaptic dopamine and abnormally prolonged post-synaptic responses. DAT-1 is a target of several psychoactive drugs (including cocaine and amphetamine) whose effects are due in part to overstimulation by aminergic neurotransmitters. DAT-1 is expressed in the eight dopaminergic neurons in C. elegans (MacGregor et al. 1997; Nass et al., 1999, 2000). We have isolated a mutant with a deletion in DAT-1 that removes most of the transmembrane domains of the protein. Deletion of this transporter might have multiple effects on dopaminergic neurotransmission. As in vertebrates, deletion of DAT might cause prolonged postsynaptic stimulation by dopamine and enhanced dopamine-dependent behaviors. On the other hand, the reduced re-uptake of dopamine into the presynaptic neuron might decrease the local concentration of dopamine and might lead to less dopamine being loaded into pre-synaptic vesicles by VMAT. This might lead to less dopamine release per stimulus although, again, that dopamine would be expected to persist longer than normal. When we examined behavior in
dat-1 mutants we found no detectable differences in a number of behaviors. However, DAT-1 mutants do show subtle behavioral differences in locomotion that are consistent with an excess of dopamine neurotransmission in at least some dopaminergic synapses. Supported by grants from NIH and OCAST.