Neurexin controls plasticity of a mature, sexually dimorphic neuron

Hart, Michael P.; Hobert, Oliver

doi:10.1038/nature25192

Cited by 76 publications

(121 citation statements)

References 41 publications

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“…elegans, but undergoes experience-dependent morphological plasticity only in males (Hart & Hobert, 2018). In studying morphologic plasticity of the GABAergic DVB neuron in adult male C. elegans (Fig.1A Guo, & Garcia, 2011).…”

Section: Adolescent Stress Alters Gabaergic Neuron Morphology By Altementioning

confidence: 99%

“…The functional impact of DVB morphologic plasticity in adulthood was previously characterized on a number of behaviors, including male spicule protraction behavior (Hart & Hobert, 2018). The spicules ( Fig.4A) protract out of the male tail to penetrate the hermaphrodite vulva during copulation, and are therefore required for successful sperm transfer (Garcia, Mehta, & Sternberg, 2001).…”

Section: Adolescent Stressors Differentially Impact Dvb Function In Mmentioning

confidence: 99%

“…The GABAergic DVB neuron synapses onto the SPC neuron as well as onto the spicule protractor muscles to inhibit spicule protraction ( Fig.4B). Therefore, DVB neurite elaboration, which adds synapses specifically onto these targets (Hart & Hobert, 2018), results in increased SPC and spicule protractor inhibition, and a delay in the time to aldicarb-induced spicule protraction. This increased time to spicule protraction serves as a readout for the amount of DVB GABAergic input (Hart & Hobert, 2018).…”

Section: Adolescent Stressors Differentially Impact Dvb Function In Mmentioning

confidence: 99%

“…The C. elegans neurexin ortholog, nrx-1, is required for starvation-induced DVB neurite outgrowth DVB neurite outgrowth in early adulthood is dependent on the ortholog of the synaptic adhesion molecule neurexin, nrx-1 (Hart & Hobert, 2018). To determine if mid-L4 stress-induced DVB neurite outgrowth is also dependent on nrx-1, I analyzed neurite outgrowth in nrx-1 mutant males.…”

Section: Adolescent Stressors Differentially Impact Dvb Function In Mmentioning

confidence: 99%

“…We recently described experience-dependent morphologic plasticity in the nematode C. elegans, where the GABAergic DVB neuron undergoes progressive experience-dependent outgrowth of axon-like neurites in adult males. This plasticity alters circuit connectivity to cause changes in male mating and defecation behaviors (Hart & Hobert, 2018). We identified the singular C. elegans ortholog of human neurexins, nrx-1, to be required in the DVB neuron for this neurite outgrowth.…”

Section: Introductionmentioning

confidence: 99%

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Stress-induced neuron remodeling reveals differential interplay between neurexin and environmental factors

2018

Preprint

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Neurexins are neuronal adhesion molecules important for synapse maturation, function, and plasticity. Neurexins have been genetically associated with neurodevelopmental disorders including autism spectrum disorders (ASDs) and schizophrenia, but can have variable penetrance and phenotypic severity. Heritability studies indicate that a significant percentage of risk for ASD and schizophrenia includes environmental factors, highlighting the poorly understood interplay between genetic and environmental factors in pathogenesis of these disorders. The singular C. elegans ortholog of human neurexins, nrx-1, controls experience-dependent morphologic remodeling of a GABAergic neuron in adult males. Here I show that this GABAergic neuron's morphology is altered in response to each of three environmental stressors (nutritional, heat, or genotoxic stress) applied during sexual maturation, but not during adulthood. Increased outgrowth of axon-like neurites following adolescent stress results from an altered morphologic plasticity that occurs upon entry into adulthood. Despite axonal remodeling being induced by each of the three stressors, only nutritional stress (starvation) impacts behavior and is dependent on neurexin/nrx-1. Heat or genotoxic stress during sexual maturation did not alter behavior despite inducing GABAergic neuron remodeling, and this remodeling was independent of neurexin/nrx-1. Remodeling induced by starvation stress was found be dependent on neuroligin/nlg-1, the canonical binding partner for neurexin/nrx-1, as well as the stress signaling transcription factors FOXO/daf-16 and HSF1/hsf-1, each of which was also found to have unique roles in remodeling induced by heat and UV stress. The differential molecular mechanisms underlying GABAergic neuron remodeling in response to different stressors, and the disparate effects of stressors on behavior, is a novel paradigm for understanding how genetics, environmental exposures, and plasticity may contribute to brain dysfunction in ASDs and schizophrenia.

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Section: Adolescent Stress Alters Gabaergic Neuron Morphology By Altementioning

confidence: 99%

Section: Adolescent Stressors Differentially Impact Dvb Function In Mmentioning

confidence: 99%

Section: Adolescent Stressors Differentially Impact Dvb Function In Mmentioning

confidence: 99%

Section: Adolescent Stressors Differentially Impact Dvb Function In Mmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stress-induced neuron remodeling reveals differential interplay between neurexin and environmental factors

2018

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Sexual Dimorphism of Gut Microbiota Dictates Therapeutics Efficacy of Radiation Injuries

Cui

Xiao

et al. 2019

Advanced Science

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Accidental or iatrogenic ionizing radiation exposure precipitates acute and chronic radiation injuries. The traditional paradigm of mitigating radiotherapy‐associated adverse side effects has ignored the gender‐specific dimorphism of patients' divergent responses. Here, the effects of sexual dimorphism on curative efficiencies of therapeutic agents is examined in murine models of irradiation injury. Oral gavage of simvastatin ameliorates radiation‐induced hematopoietic injury and gastrointestinal tract dysfunction in male mice, but adversely deteriorates these radiation syndromes in female animals. In a sharp contrast, feeding animals with high‐fat diet (HFD) elicites explicitly contrary results. High‐throughput sequencing of microbial 16S rRNA, host miRNA, and mRNA shows that simvastatin or HFD administration preventes radiation‐altered enteric bacterial taxonomic structure, preserves miRNA expression profile, and reprogrammes the spectrum of mRNA expression in small intestines of male or female mice, respectively. Notably, faecal microbiota transplantation of gut microbes from opposite sexual donors abrogates the curative effects of simvastatin or HFD in respective genders of animals. Together, these findings demonstrate that curative efficiencies of therapeutic strategies mitigating radiation toxicity might be dependent on the gender of patients, thus simvastatin or HFD might be specifically useful for fighting against radiation toxicity in a sex‐dependent fashion partly based on sex‐distinct gut microbiota composition in preclinical settings.

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Single‐Vesicle Electrochemistry Reveals Sex Difference in Vesicular Storage and Release of Catecholamine

et al. 2022

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Quantitative measurements of sex difference in vesicle chemistry (i.e., chemical storage and release) at the single-vesicle level are essential to understand sex differences in cognitive behaviors; however, such measurements are very challenging to conventional analytical methods. By using single-vesicle electrochemistry, we find the duration of single exocytotic events of chromaffin cells prepared from male rats is statistically longer than that from female rats, leading to more neurotransmitter released in the male group. Further analysis reveals that a higher percentage of vesicles in the female group release part of the neurotransmitter, i.e., partial release, during exocytosis than that in male group. This sex dimorphism in neurotransmitter release in exocytosis might relate to the sex difference in the expression of voltage-dependent calcium channels and membrane lipid composition. Our finding offers the first experimental evidence that sex dimorphism even exists in vesicle chemistry, providing a brand new viewpoint for understanding the sex dimorphism in exocytosis.

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Neurexin controls plasticity of a mature, sexually dimorphic neuron

Cited by 76 publications

References 41 publications

Stress-induced neuron remodeling reveals differential interplay between neurexin and environmental factors

Stress-induced neuron remodeling reveals differential interplay between neurexin and environmental factors

Sexual Dimorphism of Gut Microbiota Dictates Therapeutics Efficacy of Radiation Injuries

Single‐Vesicle Electrochemistry Reveals Sex Difference in Vesicular Storage and Release of Catecholamine

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