Habituation is a learned decrement in responding following repeated exposure to a stimulus. Despite its importance the mechanisms underlying habituation remain largely unknown. Repeated exposure to taps (non-localized mechanosensory stimulation) leads to habituation of a reversal withdrawal response in C. elegans that is dependent on glutamate transmission and postsynaptic AMPA receptors. Here we use high throughput behavioural analysis to characterize the role of AVR-14, an inhibitory glutamate gated chloride channel homologous to vertebrate glycine subunits that is expressed on the mechosensory neurons. Avr-14 loss of function mutants display a larger initial reversal duration in response to tap and faster habituation to tap stimuli than wild-type animals at a 10s interstimulus interval (ISI). At long ISIs (60s),
avr-14 mutants habituated significantly less than wild-type animals. The stark contrast in phenotypes at short and long ISIs necessitated analysis of habituation across ISIs (10-60s ISIs). This revealed that mutations in
avr-14 result in faster habituation at short ISIs, wild-type habituation at intermediate ISIs, and slower habituation and longer ISIs. Together these studies suggest mutations in
avr-14 alter habituation in an ISI-dependent manner. Experiments using cell-specific knockdown, rescue, and stimulation will localize the memory functions of AVR-14 to elucidate how it modulates the tap habituation circuit. These studies will determine how the inhibitory functions of glutamate mediate short-term habituation in C. elegans, furthering our understanding of the processes underlying learning and memory. .