ABSTRACT We propose to use a model circuit in Drosophila to study aminergic neuromodulation. The relatively small number of presynaptic cells combined with easy access to both pre- and post-synaptic sites will allow us to quantify the activity of each aminergic neuron, their functional relationships to post-synaptic targets and how their activities are coordinated. Recently developed molecular genetic tools will allow us to map all of the relevant receptors for the first time. New methods of preparing the tissue will allow us to identify the function of both direct and indirect regulatory pathways. Using RNAi transgenes as well as classical mutations we will define the function of all of the aminergic and glutamatergic receptors in the circuit and how they interact. Preliminary Data have uncovered unexpected complexities in this relatively simple circuit that will be relevant to a variety of other more complex circuits less amenable to the detailed analysis we propose here.