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Repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases. DEET is a safe, broad spectrum repellent, which provides complete protection over a long period of time. Despite its low cost, more affordable alternatives are highly desirable, particularly for those in endemic areas where cost is an impediment. Alternative compounds like IR 3535 and picaridin have been developed using molecular modeling, but the lack of knowledge of the molecular target(s) for DEET has retarded progress towards low cost alternatives. It is known that DEET acts at a distance as an odorant as well as by direct contact, i.e., as a tastant, although DEET reception is primarily mediated by the olfactory system. There is unambiguous evidence that olfactory receptor neurons are involved, and that an odorant receptor co-receptor Orco is essential for DEET reception. In the southern house mosquito, Culex quinquefasciatus, DEET triggers repellence by direct activation of an odorant receptor, CquiOR136, which is also sensitive to a plant defense compound, methyl jasmonate.

Ionotropic Receptors (IRs) are a large subfamily of variant ionotropic glutamate receptors present across Protostomia. While these receptors are most extensively studied for their roles in chemosensory detection, recent work has implicated two family members, IR21a and IR25a, in thermosensation in Drosophila. Here we characterize one of the most evolutionarily deeply conserved receptors, IR93a, and show that it is co-expressed and functions with IR21a and IR25a to mediate physiological and behavioral responses to cool temperatures. IR93a is also co-expressed with IR25a and a distinct receptor, IR40a, in a discrete population of sensory neurons in the sacculus, a multi-chambered pocket within the antenna. We demonstrate that this combination of receptors is required for neuronal responses to dry air and behavioral discrimination of humidity differences. Our results identify IR93a as a common component of molecularly and cellularly distinct IR pathways important for thermosensation and hygrosensation in insects.

Repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases. DEET is a safe, broad spectrum repellent, which provides complete protection over a long period of time. Despite its low cost, more affordable alternatives are highly desirable, particularly for those in endemic areas where cost is an impediment. Alternative compounds like IR 3535 and picaridin have been developed using molecular modeling, but the lack of knowledge of the molecular target(s) for DEET has retarded progress towards low cost alternatives. It is known that DEET acts at a distance as an odorant as well as by direct contact, i.e., as a tastant, although DEET reception is primarily mediated by the olfactory system. There is unambiguous evidence that olfactory receptor neurons are involved, and that an odorant receptor co-receptor Orco is essential for DEET reception. In the southern house mosquito, Culex quinquefasciatus, DEET triggers repellence by direct activation of an odorant receptor, CquiOR136, which is also sensitive to a plant defense compound, methyl jasmonate.