Oxygen is the main sensory stimulus that promotes aggregation and elicits O2- escape behaviour in C. elegans. It also constitutes a salient cue for this nematode that reprograms its behavioural strategies as well as physiology after prolonged oxygen experience. However, it is not known how other sensory modalities affect O2-escape behaviour. Moreover, the molecular details of how oxygen alters C. elegans behavioural preferences are elusive. Wild isolates of C. elegans aggregate and avoid oxygen at high concentrations, whereas both behaviours are suppressed in the N2 reference strain by a gain of function mutation in the neuropeptide receptor 1 (npr-1). This mutation, among other things, sculpts the flow of information in the O2-circuit and prevents O2-evoked Ca2+ responses in the sensory neuron ADL. Here, we perform a forward genetic screen to isolate mutants that confer O2-escape behaviour on N2 animals. Using whole-genome sequencing and genetic mapping, we identify several conserved genes not previously shown to regulate aggregation. Among these, we characterise mutants that do not show defects in O2-evoked Ca2+ responses in URX and RMG, but show increased secretion of dense-core vesicles from ADL, which could be rescued cell specifically for at least one mutant. Furthermore, we demonstrate that this increased neurosecretion is likely to results from sensitisation of ADL neurons to incoming activity from the O2-circuit. In fact, while N2 does not modulate ADL neurosecretion according to ambient oxygen levels, mutants with enhanced ADL neurosecretion acquire this feature. These mutants also display defects for other sensory modalities, including pheromone-evoked Ca2+ responses in ADL. These data provide a link between defective sensory perception and O2-escape behaviour. Reminiscent of how sensory deprivation induces homeostatic plasticity, we propose that, in sensory defective mutants, similar mechanisms might sensitise ADL to incoming activity from the O2-circuit and promote O2-escape behaviour. Moreover, we also investigate the extent to which prolonged oxygen exposure reprograms the O2-circuit. These results shed light on how changes in one sensory modality reprograms responses to other sensory modalities.