Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner
- ShanghaiTech University, China
- The University of Queensland, Australia
- College of Life Science and Technology, China
- Massachusetts General Hospital, United States
- Shanghai Jiao Tong University School of Medicine, China
Abstract
The development of functional synapses in the nervous system is important for animal physiology and behaviors, and its disturbance has been linked with many neurodevelopmental disorders. The synaptic transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of synaptic transmission remains poorly understood. Here we show that in C. elegans, the male environment increases the hermaphrodite cholinergic transmission at the neuromuscular junction (NMJ), which alters hermaphrodites' locomotion velocity and mating efficiency. We identify that the male-specific pheromones mediate this synaptic transmission modulation effect in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to the male pheromones specifically increases the accumulation of presynaptic CaV2 calcium channels and clustering of postsynaptic acetylcholine receptors at cholinergic synapses of NMJ, which potentiates cholinergic synaptic transmission. Thus, our study demonstrates a circuit mechanism for synaptic modulation and behavioral flexibility by sexual dimorphic pheromones.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided. For other information (such as primers), we already included them in the methods.
Article and author information
Author details
Funding
Basic Research Project from the Science and Technology Commission (19JC1414100)
- Xia-Jing Tong
Shanghai Pujiang Program (18PJ1407600)
- Xia-Jing Tong
Shanghai Pujiang Program (17PJ1405400)
- Qian Li
Shanghai Brain-Intelligence Project from the Science and Technology Commission of Shanghai Municipality (18JC1420302)
- Qian Li
Program for Special Appointment at Shanghai Institutions of Higher Learning (QD2018017)
- Qian Li
Innovative research team of high-level local universities in Shanghai, National Institute of Neurological Disorder and Stroke (NS32196)
- Josh M Kaplan
National Institutes of Health research grant (NEI 1R21EY029450-01)
- Josh M Kaplan
National Health and Medical Research Council (APP1122351)
- Zhi-Tao Hu
National Natural Science Foundation of China (31741054)
- Xia-Jing Tong
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Qian et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,963
- views
-
- 308
- downloads
-
- 13
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner
eLife 10:e67170.
https://doi.org/10.7554/eLife.67170
Further reading
-
- Neuroscience
Brain water homeostasis not only provides a physical protection, but also determines the diffusion of chemical molecules key for information processing and metabolic stability. As a major type of glia in brain parenchyma, astrocytes are the dominant cell type expressing aquaporin water channel. How astrocyte aquaporin contributes to brain water homeostasis in basal physiology remains to be understood. We report that astrocyte aquaporin 4 (AQP4) mediates a tonic water efflux in basal conditions. Acute inhibition of astrocyte AQP4 leads to intracellular water accumulation as optically resolved by fluorescence-translated imaging in acute brain slices, and in vivo by fiber photometry in mobile mice. We then show that aquaporin-mediated constant water efflux maintains astrocyte volume and osmotic equilibrium, astrocyte and neuron Ca2+ signaling, and extracellular space remodeling during optogenetically induced cortical spreading depression. Using diffusion-weighted magnetic resonance imaging (DW-MRI), we observed that in vivo inhibition of AQP4 water efflux heterogeneously disturbs brain water homeostasis in a region-dependent manner. Our data suggest that astrocyte aquaporin, though bidirectional in nature, mediates a tonic water outflow to sustain cellular and environmental equilibrium in brain parenchyma.
-
- Neuroscience
Neuromodulatory inputs to the hippocampus play pivotal roles in modulating synaptic plasticity, shaping neuronal activity, and influencing learning and memory. Recently, it has been shown that the main sources of catecholamines to the hippocampus, ventral tegmental area (VTA) and locus coeruleus (LC), may have overlapping release of neurotransmitters and effects on the hippocampus. Therefore, to dissect the impacts of both VTA and LC circuits on hippocampal function, a thorough examination of how these pathways might differentially operate during behavior and learning is necessary. We therefore utilized two-photon microscopy to functionally image the activity of VTA and LC axons within the CA1 region of the dorsal hippocampus in head-fixed male mice navigating linear paths within virtual reality (VR) environments. We found that within familiar environments some VTA axons and the vast majority of LC axons showed a correlation with the animals’ running speed. However, as mice approached previously learned rewarded locations, a large majority of VTA axons exhibited a gradual ramping-up of activity, peaking at the reward location. In contrast, LC axons displayed a pre-movement signal predictive of the animal’s transition from immobility to movement. Interestingly, a marked divergence emerged following a switch from the familiar to novel VR environments. Many LC axons showed large increases in activity that remained elevated for over a minute, while the previously observed VTA axon ramping-to-reward dynamics disappeared during the same period. In conclusion, these findings highlight distinct roles of VTA and LC catecholaminergic inputs in the dorsal CA1 hippocampal region. These inputs encode unique information, with reward information in VTA inputs and novelty and kinematic information in LC inputs, likely contributing to differential modulation of hippocampal activity during behavior and learning.
