scholarly journals Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner

2021 ◽  
Author(s):  
Kang-Ying Qian ◽  
Wan-Xin Zeng ◽  
Yue Hao ◽  
Xian-Ting Zeng ◽  
Haowen Liu ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Synaptic Transmission ◽  
Dependent Manner ◽  
Synaptic Modulation ◽  
C Elegans ◽  
Animal Reproduction ◽  
Male Pheromones ◽  
Cholinergic Synaptic Transmission ◽  
Cholinergic Synapses ◽  
Cgmp Signaling

SUMMARYThe development of functional synapses in the nervous system is important for animal physiology and behaviors. 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 pheromone increases the hermaphrodite cholinergic transmission at the neuromuscular junction (NMJ), which alters hermaphrodites’ locomotion velocity and mating efficiency 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 male pheromones specifically increases the accumulation of presynaptic CaV2 calcium channels and clustering of postsynaptic receptors at cholinergic synapses of NMJ, which potentiates cholinergic synaptic transmission. Thus, our study demonstrates a circuit mechanism for synaptic modulation by sexual dimorphic pheromones.

scholarly journals Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kang-Ying Qian ◽  
Wan-Xin Zeng ◽  
Yue Hao ◽  
Xian-Ting Zeng ◽  
Haowen Liu ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Synaptic Transmission ◽  
Acetylcholine Receptors ◽  
Behavioral Flexibility ◽  
Dependent Manner ◽  
C Elegans ◽  
Animal Reproduction ◽  
Male Pheromones ◽  
Cholinergic Synaptic Transmission ◽  
Cgmp Signaling

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.

Sevoflurane Blocks Cholinergic Synaptic Transmission Postsynaptically but Does Not Affect Short-term Potentiation

2005 ◽  
Vol 102 (5) ◽  
pp. 920-928 ◽  
Author(s):  
Hiroaki Naruo ◽  
Shin Onizuka ◽  
David Prince ◽  
Mayumi Takasaki ◽  
Naweed I. Syed
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Fluorescent Imaging ◽  
Posttetanic Potentiation ◽  
Dependent Manner ◽  
General Anesthetics ◽  
Short Term ◽  
Concentration Dependent Manner ◽  
Cholinergic Synaptic Transmission ◽  
Term Potentiation

Background As compared with their effects on both inhibitory and excitatory synapses, little is known about the mechanisms by which general anesthetics affect synaptic plasticity that forms the basis for learning and memory at the cellular level. To test whether clinically relevant concentrations of sevoflurane affect short-term potentiation involving cholinergic synaptic transmission, the soma-soma synapses between identified, postsynaptic neurons were used. Methods Uniquely identifiable neurons visceral dorsal 4 (presynaptic) and left pedal dorsal 1 (postsynaptic) of the mollusk Lymnaea stagnalis were isolated from the intact ganglion and paired overnight in a soma-soma configuration. Simultaneous intracellular recordings coupled with fluorescent imaging of the FM1-43 dye were made in either the absence or the presence of sevoflurane. Results Cholinergic synapses, similar to those observed in vivo, developed between the neurons, and the synaptic transmission exhibited classic short-term, posttetanic potentiation. Action potential-induced (visceral dorsal 4), 1:1 excitatory postsynaptic potentials were reversibly and significantly suppressed by sevoflurane in a concentration-dependent manner. Fluorescent imaging with the dye FM1-43 revealed that sevoflurane did not affect presynaptic exocytosis or endocytosis; instead, postsynaptic nicotinic acetylcholine receptors were blocked in a concentration-dependent manner. To test the hypothesis that sevoflurane affects short-term potentiation, a posttetanic potentiation paradigm was used, and synaptic transmission was examined in either the presence or the absence of sevoflurane. Although 1.5% sevoflurane significantly reduced synaptic transmission between the paired cells, it did not affect the formation or retention of posttetanic potentiation at this synapse. Conclusions This study demonstrates that sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term synaptic plasticity at the visceral dorsal 4-left pedal dorsal 1 synapse.

scholarly journals The Ror Receptor Tyrosine Kinase CAM-1 Is Required for ACR-16-Mediated Synaptic Transmission at the C. elegans Neuromuscular Junction

Neuron ◽  
2005 ◽  
Vol 46 (4) ◽  
pp. 581-594 ◽  
Author(s):  
Michael M. Francis ◽  
Susan P. Evans ◽  
Michael Jensen ◽  
David M. Madsen ◽  
Joel Mancuso ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Synaptic Transmission ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
C Elegans

scholarly journals The Dysferlin homolog fer‐1 is required for efficient cholinergic synaptic transmission in C. elegans

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Predrag Krajacic ◽  
Matias Mosqueira ◽  
Jane Hermanowski ◽  
Olga Lozynska ◽  
Xiaoning Shen ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
C Elegans ◽  
Cholinergic Synaptic Transmission

scholarly journals Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rowan P. Rimington ◽  
Jacob W. Fleming ◽  
Andrew J. Capel ◽  
Patrick C. Wheeler ◽  
Mark P. Lewis
Keyword(s):  
Neuromuscular Junction ◽  
Motor Neuron ◽  
Motor Unit ◽  
Motor Nerve ◽  
Motor Units ◽  
Extracellular Matrices ◽  
Synaptic Membrane ◽  
Type I ◽  
Dependent Manner ◽  
Human Motor

AbstractInvestigations of the human neuromuscular junction (NMJ) have predominately utilised experimental animals, model organisms, or monolayer cell cultures that fail to represent the physiological complexity of the synapse. Consequently, there remains a paucity of data regarding the development of the human NMJ and a lack of systems that enable investigation of the motor unit. This work addresses this need, providing the methodologies to bioengineer 3D models of the human motor unit. Spheroid culture of iPSC derived motor neuron progenitors augmented the transcription of OLIG2, ISLET1 and SMI32 motor neuron mRNAs ~ 400, ~ 150 and ~ 200-fold respectively compared to monolayer equivalents. Axon projections of adhered spheroids exceeded 1000 μm in monolayer, with transcription of SMI32 and VACHT mRNAs further enhanced by addition to 3D extracellular matrices in a type I collagen concentration dependent manner. Bioengineered skeletal muscles produced functional tetanic and twitch profiles, demonstrated increased acetylcholine receptor (AChR) clustering and transcription of MUSK and LRP4 mRNAs, indicating enhanced organisation of the post-synaptic membrane. The number of motor neuron spheroids, or motor pool, required to functionally innervate 3D muscle tissues was then determined, generating functional human NMJs that evidence pre- and post-synaptic membrane and motor nerve axon co-localisation. Spontaneous firing was significantly elevated in 3D motor units, confirmed to be driven by the motor nerve via antagonistic inhibition of the AChR. Functional analysis outlined decreased time to peak twitch and half relaxation times, indicating enhanced physiology of excitation contraction coupling in innervated motor units. Our findings provide the methods to maximise the maturity of both iPSC motor neurons and primary human skeletal muscle, utilising cell type specific extracellular matrices and developmental timelines to bioengineer the human motor unit for the study of neuromuscular junction physiology.

A Cuticle Collagen Encoded by the lon-3 Gene May Be a Target of TGF-β Signaling in Determining Caenorhabditis elegans Body Shape

Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1631-1639
Author(s):  
Yo Suzuki ◽  
Gail A Morris ◽  
Min Han ◽  
William B Wood
Keyword(s):  
Caenorhabditis Elegans ◽  
Body Shape ◽  
Small Body ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Cellular Mechanisms ◽  
C Elegans ◽  
Gene Expression Analyses ◽  
Dose Dependent

Abstract The signaling pathway initiated by the TGF-β family member DBL-1 in Caenorhabditis elegans controls body shape in a dose-dependent manner. Loss-of-function (lf) mutations in the dbl-1 gene cause a short, small body (Sma phenotype), whereas overexpression of dbl-1 causes a long body (Lon phenotype). To understand the cellular mechanisms underlying these phenotypes, we have isolated suppressors of the Sma phenotype resulting from a dbl-1(lf) mutation. Two of these suppressors are mutations in the lon-3 gene, of which four additional alleles are known. We show that lon-3 encodes a collagen that is a component of the C. elegans cuticle. Genetic and reporter-gene expression analyses suggest that lon-3 is involved in determination of body shape and is post-transcriptionally regulated by the dbl-1 pathway. These results support the possibility that TGF-β signaling controls C. elegans body shape by regulating cuticle composition.

scholarly journals H3K27 modifiers regulate lifespan in C. elegans in a context-dependent manner

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abigail R. R. Guillermo ◽  
Karolina Chocian ◽  
Gavriil Gavriilidis ◽  
Julien Vandamme ◽  
Anna Elisabetta Salcini ◽  
...  
Keyword(s):  
Lifespan Extension ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Animal Cells ◽  
C Elegans ◽  
Specific Effects ◽  
Aberrant Gene Expression ◽  
Lysine Methyltransferase ◽  
Epigenetic Signatures ◽  
Aberrant Gene

Abstract Background Evidence of global heterochromatin decay and aberrant gene expression in models of physiological and premature ageing have long supported the “heterochromatin loss theory of ageing”, which proposes that ageing is aetiologically linked to, and accompanied by, a progressive, generalised loss of repressive epigenetic signatures. However, the remarkable plasticity of chromatin conformation suggests that the re-establishment of such marks could potentially revert the transcriptomic architecture of animal cells to a “younger” state, promoting longevity and healthspan. To expand our understanding of the ageing process and its connection to chromatin biology, we screened an RNAi library of chromatin-associated factors for increased longevity phenotypes. Results We identified the lysine demethylases jmjd-3.2 and utx-1, as well as the lysine methyltransferase mes-2 as regulators of both lifespan and healthspan in C. elegans. Strikingly, we found that both overexpression and loss of function of jmjd-3.2 and utx-1 are all associated with enhanced longevity. Furthermore, we showed that the catalytic activity of UTX-1, but not JMJD-3.2, is critical for lifespan extension in the context of overexpression. In attempting to reconcile the improved longevity associated with both loss and gain of function of utx-1, we investigated the alternative lifespan pathways and tissue specificity of longevity outcomes. We demonstrated that lifespan extension caused by loss of utx-1 function is daf-16 dependent, while overexpression effects are partially independent of daf-16. In addition, lifespan extension was observed when utx-1 was knocked down or overexpressed in neurons and intestine, whereas in the epidermis, only knockdown of utx-1 conferred improved longevity. Conclusions We show that the regulation of longevity by chromatin modifiers can be the result of the interaction between distinct factors, such as the level and tissue of expression. Overall, we suggest that the heterochromatin loss model of ageing may be too simplistic an explanation of organismal ageing when molecular and tissue-specific effects are taken into account.

Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress

2005 ◽  
Vol 288 (2) ◽  
pp. C467-C474 ◽  
Author(s):  
S. Todd Lamitina ◽  
Kevin Strange
Keyword(s):  
Insulin Signaling ◽  
Stress Resistance ◽  
Molecular Mechanisms ◽  
Organic Osmolytes ◽  
Dependent Manner ◽  
Animal Cells ◽  
Hypertonic Stress ◽  
C Elegans ◽  
Downstream Target ◽  
Molecular Damage

All cells adapt to hypertonic stress by regulating their volume after shrinkage, by accumulating organic osmolytes, and by activating mechanisms that protect against and repair hypertonicity-induced damage. In mammals and nematodes, inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF-16/FOXO transcription factor, resulting in increased life span and resistance to some types of stress. We tested the hypothesis that inhibition of insulin signaling in Caenorhabditis elegans also increases hypertonic stress resistance. Genetic inhibition of DAF-2 or its downstream target, the AGE-1 phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not inhibited by or required for adaptation to hypertonic conditions. Microarray studies have identified 263 genes that are transcriptionally upregulated by DAF-16 activation. We identified 14 DAF-16-upregulated genes by RNA interference screening that are required for age- 1 hypertonic stress resistance. These genes encode heat shock proteins, proteins of unknown function, and trehalose synthesis enzymes. Trehalose levels were elevated approximately twofold in age- 1 mutants, but this increase was insufficient to prevent rapid hypertonic shrinkage. However, age- 1 animals unable to synthesize trehalose survive poorly under hypertonic conditions. We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf- 2/ age- 1 mutants. Elevated levels of solutes such as trehalose may also function in a cytoprotective manner. Our studies provide novel insights into stress resistance in animal cells and a foundation for new studies aimed at defining molecular mechanisms underlying these essential processes.

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