Information about nutrient availability is assessed via largely unknown mechanisms to drive developmental decisions, including the choice of Caenorhabditis elegans larvae to enter into the reproductive cycle or the dauer stage. In this study, we show that CMK-1 CaMKI regulates the dauer decision as a function of feeding state. CMK-1 acts cell-autonomously in the ASI, and non cell-autonomously in the AWC, sensory neurons to regulate expression of the growth promoting daf-7 TGF-β and daf-28 insulin-like peptide (ILP) genes, respectively. Feeding state regulates dynamic subcellular localization of CMK-1, and CMK-1-dependent expression of anti-dauer ILP genes, in AWC. A food-regulated balance between anti-dauer ILP signals from AWC and pro-dauer signals regulates neuroendocrine signaling and dauer entry; disruption of this balance in cmk-1 mutants drives inappropriate dauer formation under well-fed conditions. These results identify mechanisms by which nutrient information is integrated in a small neuronal network to modulate neuroendocrine signaling and developmental plasticity.DOI:
http://dx.doi.org/10.7554/eLife.10110.001
SUMMARY
Experiences during early development can influence neuronal functions and modulate adult behaviors [1, 2]. However, the molecular mechanisms underlying the long-term behavioral effects of these early experiences are not fully understood. The C. elegans ascr#3 (asc-0394C9, C9) pheromone triggers avoidance behavior in adult hermaphrodites [3–7]. Here, we show that hermaphrodites that are briefly exposed to ascr#3 immediately after birth exhibit increased ascr#3-specific avoidance as adults indicating that ascr#3-experienced animals form a long lasting memory or imprint of this early ascr#3 exposure [8]. Ascr#3 imprinting is mediated by increased synaptic activity between the ascr#3-sensing ADL neurons and their post-synaptic SMB motor neuron partners via increased expression of the odr-2 GPI-linked signaling gene in the SMB neurons. Our study suggests that the memory for early ascr#3 experience is imprinted via alteration of activity of a single synaptic connection, that in turn shapes experience-dependent plasticity in adult ascr#3 responses.
Pyrethroid compounds are widely used in household insecticides and agricultural pesticides. Recent studies, however, report that pyrethroid exposures affect neurobehavioral function in animals and may be associated with adverse neurocognitive development in children. This study aimed to examine the association between pyrethroid exposure and cognitive dysfunction in older adults using a well-defined general population. We analyzed data from 336 individuals, aged 60–84 years, who participated in the National Health and Nutrition Examination Survey 2001–2002. We used urinary 3-phenoxybenzoic acid (3-PBA) concentration as a biomarker of pyrethroid exposures and assessed cognitive function with the digit–symbol coding test. The geometric means (±geometric standard errors) of creatinine-uncorrected and corrected urinary 3-PBA were 0.30 (±0.87) μg/L and 0.36 (±0.89) μg/g. After adjusting for sociodemographic factors, higher 3-PBA concentrations (> vs. ≤0.30 μg/g creatinine (median)) were associated with lower scores of cognitive function (−3.83 95% confidence interval: −7.11, −0.54). Significance was persistent after additionally adjusting for physical activity and smoking pack-year (−3.76 95% CI: −7.16, −0.36) and further adjusting for BMI and presence of hypertension and diabetes (−3.82 95% CI: −6.92, −0.71). Our findings suggest that pyrethroid exposure is associated with cognitive dysfunction in older adults.
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