Our studies suggest that w and mini-w specifically impact climbing in the presence of ethanol. One possible explanation for the contrasting effects of w and mini-w on climbing versus walking could be that these two behaviors are driven by different sets of neurons and that w and mini-w selectively affect the function of the neurons involved in climbing. The selective role of w and mini-w in climbing neurons could be related to cell-specific expression of the genes brown and scarlet (known partners for the white transporter (Ewart et al., 1994)), neuron-specific release of or responses to nitric oxide, dopamine, serotonin or histamine (neuromodulators known or suspected to be altered in w mutants (Borycz et al., 2008; Campbell and Nash, 2001; Sitaraman et al., 2008)), or transport of cGMP (Evans et al., 2008). Alternatively, it is possible that climbing is simply more physically demanding than walking; if loss of w causes partial defects in neuronal function, those defects might be revealed during climbing in the presence of ethanol in eRING assays. Additional studies are needed to address these and other possible mechanisms for the effect of w and mini-w in ethanol sensitivity measured in eRING assays.
