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Slaughter, J.

Publications and source records attributed to Slaughter, J..

2 recordsLinked to original sources

Wireless Magnetomechanical Stimulation of Targeted Vagal Gut-Brain Circuits

Causal manipulation of gut-brain neural circuits empowers studies of metabolism and interoception. However, the anatomy and cytoarchitecture of peripheral ganglia relaying gut-brain circuits pose challenges to deployment of optical or electrical stimulation probes. To enable implant-free, cell-type specific, and temporally precise control of defined gut-brain pathways, we develop a neuromodulation platform based on magnetic nanodiscs (MNDs) targeted to peripheral neurons via genetically delivered anchoring moieties. The anchored MNDs selectively transduce externally applied weak magnetic fields to mechanical torque, thereby activating endogenous mechanosensitive pathways in specified cell types with sub-second latency. When targeted to nodose ganglia neurons expressing oxytocin or glucagon-like peptide 1 receptors, MND-mediated stimulation enables robust and reversible activation of gut-brain signaling, which engages hindbrain satiety circuits and regulates feeding behavior. These findings establish MND-mediated stimulation as a genetically targetable, implant-free strategy for modulating gut-brain neural circuits and highlight its potential in studies of brain-body physiology and bioelectronic medicines.

bioengineering↗

Thermosensory behaviors of the free-living life stages of Strongyloides species support parasitism in tropical environments

Soil-transmitted parasitic nematodes infect over 1 billion people worldwide and are a common source of neglected disease. Strongyloides stercoralis is a potentially fatal skin-penetrating human parasite that is endemic to tropical and subtropical regions around the world. The complex life cycle of Strongyloides species is unique among human-parasitic nematodes in that it includes a single free-living generation featuring soil-dwelling, bacterivorous adults whose progeny all develop into infective larvae. The sensory behaviors that enable free-living Strongyloides adults to navigate and survive soil environments are unknown. S. stercoralis infective larvae display parasite-specific sensory-driven behaviors, including robust attraction to mammalian body heat. In contrast, the free-living model nematode Caenorhabditis elegans displays thermosensory behaviors that guide adult worms to stay within a physiologically permissive range of environmental temperatures. Do S. stercoralis and C. elegans free-living adults, which experience similar environmental stressors, display common thermal preferences? Here, we characterize the thermosensory behaviors of the free-living adults of S. stercoralis as well as those of the closely related rat parasite, Strongyloides ratti. We find that Strongyloides free-living adults are exclusively attracted to near-tropical temperatures, despite their inability to infect mammalian hosts. We further show that lifespan is shorter at higher temperatures for free-living Strongyloides adults, similar to the effect of temperature on C. elegans lifespan. However, we also find that the reproductive potential of the free-living life stage is enhanced at warmer temperatures, particularly for S. stercoralis. Together, our results reveal a novel role for thermotaxis to maximize the infectious capacity of obligate parasites and provide insight into the biological adaptations that may contribute to their endemicity in tropical climates. Author SummarySoil-transmitted parasitic nematodes infect over 1 billion people and are a major source of neglected disease, particularly in the worlds most resource-limited communities. For most parasitic nematode species, reproductive adults exclusively reside within host animals. Species in the genus Strongyloides have a unique step in their life cycle that features soil-dwelling, non-parasitic adults. Previous studies of the free-living model nematode Caenorhabditis elegans have identified temperature as an important factor in ability of free-living nematodes to survive and reproduce in the environment. Our study investigates how the thermosensory behaviors of Strongyloides free-living adults contribute to their survival as well as their role in amplifying the quantity of infective larvae in the soil. We show that Strongyloides free-living adults display broad thermophilic preferences that are highly distinct from those of C. elegans adults. We also present the first evidence that thermotaxis acts as a robust mechanism for maximizing the infectious capacity of Strongyloides species located in tropical climates.

neuroscience↗