Figure 9. A Model for LN_v and LMO Regulation of Cocaine Sensitivity.

(A) In wild type, LN_vs modulate locomotor responses via electrical activity and synaptic transmission. We propose a model in which cocaine acts to directly increase LN_v activity. Upon cocaine administration, synaptic DA concentrations are increased (via cocaine's inhibition of the plasma membrane DA transporter). Activation of presumed DA receptors on the LN_v (dark arrowheads) stimulates electrical activity and subsequent synaptic output. This activity contributes to the behavioral response of the fly to cocaine.

(B) LN_v ablations eliminate LN_v contribution to the cocaine response, reducing cocaine sensitivity.

(C) In our model, Lmo loss-of-function mutants (Lmo^LOF), which have increased cocaine sensitivity, have increased activity/output during the cocaine response. This increased activity may be mediated by increases in receptor content on the LN_v or by recruitment of other LN_vs that normally do not participate in the cocaine response.

(D) Lmo gain-of-function mutants (Lmo^GOF) mutants have reduced LN_v output and reduced cocaine sensitivity. This could also result from a reduction in receptor density.