One of the greatest challenges in determining the mode-of-action (MOA) of an insecticide is the progression from having characterised the physiological effect of the compound, to a positive identification of its target protein. This is particularly true when the target is novel. This leap of understanding typically relies on radioligand binding assays showing an interaction with a drug of known MOA, or forward genetics approaches identifying resistance conferring mutations in a closely linked gene. Both of these approaches can be expensive and will occasionally fail due to the nature of the chemistry, the specificity of the chemical for its target or targets, or the particular qualities of the MOA. Electrophysiology in a genetically tractable model system like Drosophila could employ elements of both these approaches by looking directly at the effects of both drugs of known MOA, and genetic lesions of known phenotype, on the physiological action of the insecticide. Experiments of this type could provide a useful steer for both binding studies and forward genetics approaches and represent a viable alternative method should these other approaches prove unsuitable. However, to date there are no straightforward electrophysiological assays in Drosophila that will allow direct measurement of the effects of insecticides at identified synapses in the nervous system. In this project we will develop such an assay by recording both spontaneous and evoked activity through the giant fibre system (GFS), a neural circuit that mediates escape responses in adult flies. In particular we will record spontaneous miniature excitatory junction potentials (mEJPs) and post-synaptic potentials (PSPs) from an indirect flight muscle (DLM) in adult flies to determine synaptic efficacy at the neuromuscular junction (NMJ) and CNS function. We will then use this assay to characterise the efffects of insecticides.