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.

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.

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 Adrenoceptors Modulate Cholinergic Synaptic Transmission at the Neuromuscular Junction

2021 ◽  
Vol 22 (9) ◽  
pp. 4611
Author(s):  
Ellya Bukharaeva ◽  
Venera Khuzakhmetova ◽  
Svetlana Dmitrieva ◽  
Andrei Tsentsevitsky
Keyword(s):  
Neuromuscular Junction ◽  
Neurodegenerative Diseases ◽  
Acetylcholine Receptors ◽  
Molecular Mechanisms ◽  
Acetylcholine Release ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Nerve Terminals ◽  
Adrenergic Agents ◽  
Cholinergic Synaptic Transmission

Adrenoceptor activators and blockers are widely used clinically for the treatment of cardiovascular and pulmonary disorders. More recently, adrenergic agents have also been used to treat neurodegenerative diseases. Recent studies indicate a location of sympathetic varicosities in close proximity to neuromuscular junctions. The pressing question is whether there could be any effects of endo- or exogenous catecholamines on cholinergic neuromuscular transmission. It was shown that the pharmacological stimulation of adrenoceptors, as well as sympathectomy, can affect both acetylcholine release from motor nerve terminals and the functioning of postsynaptic acetylcholine receptors. In this review, we discuss the recent data regarding the effects of adrenergic drugs on neurotransmission at the neuromuscular junction. The elucidation of the molecular mechanisms by which the clinically relevant adrenomimetics and adrenoblockers regulate quantal acetylcholine release from the presynaptic nerve terminals and postsynaptic sensitivity may help in the design of highly effective and well-tolerated sympathomimetics for treating a number of neurodegenerative diseases accompanied by synaptic defects.

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 MACF1 links Rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses

2019 ◽  
Vol 218 (5) ◽  
pp. 1686-1705 ◽  
Author(s):  
Julien Oury ◽  
Yun Liu ◽  
Ana Töpf ◽  
Slobodanka Todorovic ◽  
Esthelle Hoedt ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Acetylcholine Receptors ◽  
Postsynaptic Membrane ◽  
Scaffolding Protein ◽  
Actin Binding ◽  
Dependent Manner ◽  
Neuromuscular Synapses ◽  
Synaptic Differentiation ◽  
Associated Proteins ◽  
Congenital Myasthenia

Complex mechanisms are required to form neuromuscular synapses, direct their subsequent maturation, and maintain the synapse throughout life. Transcriptional and post-translational pathways play important roles in synaptic differentiation and direct the accumulation of the neurotransmitter receptors, acetylcholine receptors (AChRs), to the postsynaptic membrane, ensuring for reliable synaptic transmission. Rapsyn, an intracellular peripheral membrane protein that binds AChRs, is essential for synaptic differentiation, but how Rapsyn acts is poorly understood. We screened for proteins that coisolate with AChRs in a Rapsyn-dependent manner and show that microtubule actin cross linking factor 1 (MACF1), a scaffolding protein with binding sites for microtubules (MT) and actin, is concentrated at neuromuscular synapses, where it binds Rapsyn and serves as a synaptic organizer for MT-associated proteins, EB1 and MAP1b, and the actin-associated protein, Vinculin. MACF1 plays an important role in maintaining synaptic differentiation and efficient synaptic transmission in mice, and variants in MACF1 are associated with congenital myasthenia in humans.

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.

Sign in / Sign up

Export Citation Format

Share Document