Context-dependent reversal of odorant preference is driven by inversion of the response in a single sensory neuron type.

The valence and salience of individual odorants are modulated by an animal's innate preferences, learned associations, and internal state, as well as by the context of odorant presentation. The mechanisms underlying context-dependent flexibility in odor valence are not fully understood. Here, we show that the behavioral response of Caenorhabditis elegans to bacterially produced medium-chain alcohols switches from attraction to avoidance when presented in the background of a subset of additional attractive chemicals. This context-dependent reversal of odorant preference is driven by cell-autonomous inversion of the response to these alcohols in the single AWC olfactory neuron pair. We find that while medium-chain alcohols inhibit the AWC olfactory neurons to drive attraction, these alcohols instead activate AWC to promote avoidance when presented in the background of a second AWC-sensed odorant. We show that these opposing responses are driven via engagement of distinct odorant-directed signal transduction pathways within AWC. Our results indicate that context-dependent recruitment of alternative intracellular signaling pathways within a single sensory neuron type conveys opposite hedonic valences, thereby providing a robust mechanism for odorant encoding and discrimination at the periphery.

Thermosensation: Human Parasitic Nematodes Use Heat to Hunt Hosts.

Temperature is a critical host-emitted cue for many parasitic species. A recent study shows that skin-penetrating human parasitic hookworms and threadworms exhibit adaptive host-seeking behaviors that are based on their temperature experience, opening up possibilities for new intervention strategies.

The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson's disease.

Parkinson's disease (PD), caused by selective loss of dopaminergic (DA) neurons in the substantia nigra, is the most common movement disorder with no cure or effective treatment. Exposure to the mitochondrial complex I inhibitor rotenone recapitulates pathological hallmarks of PD in rodents and selective loss of DA neurons in Drosophila. However, mechanisms underlying rotenone toxicity are not completely resolved. We previously reported a neuroprotective effect of human uncoupling protein 2 (hUCP2) against rotenone toxicity in adult fly DA neurons. In the current study, we show that increased mitochondrial fusion is protective from rotenone toxicity whereas increased fission sensitizes the neurons to rotenone-induced cell loss in vivo. In primary DA neurons, rotenone-induced mitochondrial fragmentation and lethality is attenuated as the result of hucp2 expression. To test the idea that the neuroprotective mechanism of hUCP2 involves modulation of mitochondrial dynamics, we detect preserved mitochondrial network, mobility and fusion events in hucp2 expressing DA neurons exposed to rotenone. hucp2 expression also increases intracellular cAMP levels. Thus, we hypothesize that cAMP-dependent protein kinase (PKA) might be an effector that mediates hUCP2-associated neuroprotection against rotenone. Indeed, PKA inhibitors block preserved mitochondrial integrity, movement and cell survival in hucp2 expressing DA neurons exposed to rotenone. Taken together, we present strong evidence identifying a hUCP2-PKA axis that controls mitochondrial dynamics and survival in DA neurons exposed to rotenone implicating a novel therapeutic strategy in modifying the progression of PD pathogenesis.