Behavior requires the precise coordination of structural and functional properties of neuronal circuits, made up of neurons connected by synapses. Many neuronal and synaptic genes are associated with Autism Spectrum (AS) and schizophrenia (SCZ), suggesting that dysregulation of circuits may underlie characteristic behavioral phenotypes. Here, we ask if and how synaptic genes associated with AS/SCZ control behavior. Specifically, we are testing the role of conserved AS/SCZ genes in the C. elegans behavioral response to a simple external stressor: food deprivation. Using a PDMS fabricated "WorMotel" and computer vision image analysis, we record worm activity over 8 hours in fed or food-deprived conditions and find that food deprivation results in a sustained increase in activity in control worms that is easily quantifiable and reproducible. Ongoing high-throughput analysis of many conserved AS/SCZ genes using this paradigm, identified that
nrx-1 is required for the behavioral response to food deprivation. Multiple loss of function alleles of
nrx-1, the orthologue of the human synaptic adhesion molecule, NRXN1, resulted in reduced activity in response to food deprivation and octopamine, a candidate neuromodulator for this behavior. We find that expression of NRX-1 in all neurons rescues the mutant phenotype response to food deprivation conditions. Interestingly, mutation of the canonical binding partner of
nrx-1,
nlg-1 (NLGN3), does not alter behavioral response to food deprivation. However,
nrx-1;
nlg-1 double mutants have a normal food deprivation response, demonstrating that the
nrx-1 phenotype is dependent on
nlg-1. We are currently analyzing relevant neurons and synapses for changes that may underlie the altered response to food deprivation, in both wildtype and
nrx-1 mutants. Our results suggest
nrx-1 is involved in the response to the crucial external stimuli of food through a potentially novel function in octopamine signaling. Our work will elucidate the circuit and molecular mechanisms underlying the role of
nrx-1 on this behavior. Together with ongoing work on additional genes, we will identify overlap and interactions for AS/SCZ genes in a simple circuit and behavior and uncover novel molecular mechanisms for these genes in behavior generation.