Convulsions in C. elegans , as we have defined them, are simultaneous repetitive contractions of body wall muscles. The largest class of mutants that present a convulsion phenotype have contractions which are restricted to anterior portions of the worm. Our initial list of anterior convulsers originated from a mutagenesis screen for mutants sensitize to neurostimulant ( e.g., pentylenetetrazole or pilocarpine). Roughly three-quarters of the mutant alleles resulted in anteriorly-restricted convulsions. (The remaining quarter display full body convulsions and represent new alleles of unc-43 1 .) Phenotypic analysis revealed that every mutant had secondary drug-independent locomotion phenotypes. This led us to expand our search for convulsers to include the set of already identified uncoordinated mutants. Roughly a quarter of these showed some convulsion-sensitivity to drug treatment. These mutants define three functional classes: defects in GABAergic neurotransmission ( e.g., unc-25 ), in general synaptic function ( e.g., unc-32 , unc-64 ) and in early axonal guidance ( e.g., unc-76 ). The head of the worm receives a multitude of synaptic inputs from environmental and internal cues. Head muscles are either innervated by motor neurons localized in the nerve ring or the ventral nerve cord 2 . Based on our analysis of the full body convulsion phenotype which implicates the involvement of ventral cord motor neurons 1 , we hypothesize that anterior convulsions are likewise the result of motor neuron dysfunction but only of those that innervate anterior muscle groups. Furthermore, we believe that disruption of GABAergic signaling may be the common thread that links the three functional groups found in our screens. This suggests that the RME inhibitory motor neurons (GABA containing neurons) may be solely or partially responsible for mediating anterior convulsions. We are in the process of combining neuron-specific promoter rescue and double mutant analysis to verify this hypothesis. These experiments broaden our worm model of mechanisms underlying simultaneous excitation of neuronal networks. Recurrent and aberrant neuronal synchrony is the cause of human and mammalian epilepsies and our model has striking parallels with the current mouse model of epilepsy. For instance, there are mouse knockouts that represent the same functional classes we found in our screens ( e.g., GAD65 3 , synapsin I 4 , uPAR 5 ). We believe that we are characterizing evolutionarily ancient strategies for coordinating and controlling nervous system synchronizations. Our use of C. elegans , as a well-studied and tractable model organism combining sophisticated genetics and a mapped nervous system 2 may be a powerful way to characterize key molecular components controlling seizures and perhaps identify new drug targets for treatment. 1 See abstract McCormick, A.V. et al. (2004). Molecular analysis of UNC-43 control of neuronal synchrony in C. elegans . West Coast Worm Meeting 2 White, J.G., et al. (1986). Phil. Trans. R. Soc. Lond. 314:1-340 3 Kash S.F., et al. (1997). PNAS 94:14060-14065 4 Terada, S. et al. (1999). J Cell Biol 145:1039-1048 5 Powell, E.M. et al. (2003). J Neurosci 23:622-631