The functional organization of motor nerve terminals

Slater, Clarke R.

doi:10.1016/j.pneurobio.2015.09.004

Cited by 62 publications

(55 citation statements)

References 377 publications

(166 reference statements)

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“…Taken together, our physiological measurements are consistent with previous findings [23,38–40,49,50] regarding the relationship between synaptic size and synaptic strength and further validate the morphometric differences between anatomically defined muscles that we have reported here.…”

Section: Resultssupporting

confidence: 92%

“…Likewise, MEPP amplitude (quantal size), corrected to a standard resting membrane potential of −80 mV, was about 45% greater in IS (1.12 ± 0.13 mV, n = 33 fibres, N = 2 muscles) than in LAL (0.76 mV ± 0.06 mV, n = 47 fibres, N = 3 muscles, p < 0.01), consistent with previous reports [23]. The mean quantal content of the initial EPPs, calculated after correction of EPP amplitudes for nonlinear summation and resting potential, was about 85% larger in LAL (67.7 ± 6.2 quanta, n = 45 fibres, N = 3 muscles) than in IS (37.3 ± 2.4 quanta, n = 33 fibres, N = 2 muscles, p < 0.0001), consistent with the well-established correlation between quantal content and nerve terminal area at NMJs [23,38–40,49,50]. …”

Section: Resultssupporting

confidence: 84%

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NMJ-morph reveals principal components of synaptic morphology influencing structure–function relationships at the neuromuscular junction

et al. 2016

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The ability to form synapses is one of the fundamental properties required by the mammalian nervous system to generate network connectivity. Structural and functional diversity among synaptic populations is a key hallmark of network diversity, and yet we know comparatively little about the morphological principles that govern variability in the size, shape and strength of synapses. Using the mouse neuromuscular junction (NMJ) as an experimentally accessible model synapse, we report on the development of a robust, standardized methodology to facilitate comparative morphometric analysis of synapses (‘NMJ-morph’). We used NMJ-morph to generate baseline morphological reference data for 21 separate pre- and post-synaptic variables from 2160 individual NMJs belonging to nine anatomically distinct populations of synapses, revealing systematic differences in NMJ morphology between defined synaptic populations. Principal components analysis revealed that overall NMJ size and the degree of synaptic fragmentation, alongside pre-synaptic axon diameter, were the most critical parameters in defining synaptic morphology. ‘Average’ synaptic morphology was remarkably conserved between comparable synapses from the left and right sides of the body. Systematic differences in synaptic morphology predicted corresponding differences in synaptic function that were supported by physiological recordings, confirming the robust relationship between synaptic size and strength.

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 84%

NMJ-morph reveals principal components of synaptic morphology influencing structure–function relationships at the neuromuscular junction

et al. 2016

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“…5b). This result strengthens previous information indicating that ACh recycling and vesicular release during the course of a tetanus is dependent on choline uptake by HChT [6,8,9] and is in keeping with the theory that selective inhibition of HChT causes a myasthenia-like condition [10]. Similarly to that observed in myographic recordings, pretreatment with HC-3 (4 μmol/L) prevented the inhibitory action of NEO (0.5 μmol/L) on transmitter exocytosis evoked by 50-Hz tetanic bursts (Fig.…”

Section: Resultssupporting

confidence: 91%

“…Using myographic recordings and real-time video microscopy with the FM4-64 fluorescent dye as a measure of transmitter exocytosis, we show here for the first time that the paradoxical NEO-induced tetanic fade reduction from control may be partially attenuated upon inhibition of HChT with HC-3. We surmise that our observation may be due to the fact that the inhibition of HChT leads to a significant reduction in ACh recycling and vesicular release per pulse during high-frequency trains [6,8], as suggested by our video microscopy assay. In spite of the primary tests using high doses of HC-3 prompted for a post-synaptic neuromuscular blocking action of this drug [7], experiments elegantly designed by Elmqvist and Quastel [9] using intracellular electrophysiological recordings showed that lower doses of HC-3 (such as the one tested in our study, e.g., 4 µmol/L) exert predominant effects on ACh synthesis leading to a progressive decline of transmitter release from motor nerve terminals stimulated at high frequency rates, without affecting the postsynaptic transmitter chemosensitivity.…”

Section: Discussionmentioning

confidence: 61%

“…Under physiological conditions, choline uptake via the Na + -dependent high-affinity transporter (HChT) is the rate-limiting step for ACh synthesis [3][4][5]. In addition, it has been demonstrated that ACh recycling and vesicular release during high-frequency stimulation of cholinergic nerves is highly dependent on the choline uptake by HChT [6,7]. Impairment of the HChT function causes a progressive decay in the amount of ACh released per pulse during high-frequency stimuli [8,9], which may be a cause for the prevalence of myasthenia-like syndromes [10].…”

mentioning

confidence: 99%

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Tetanic Facilitation of Neuromuscular Transmission by Adenosine A<sub>2A</sub> and Muscarinic M<sub>1</sub> Receptors is Dependent on the Uptake of Choline via High-Affinity Transporters

Castellão-Santana¹,

Abiko²,

Ambiel³

et al. 2018

Pharmacology

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Background/Aims: In this study, we evaluated the functional impact of facilitatory presynaptic adenosine A_2A and muscarinic M₁ receptors in the recovery of neuromuscular tetanic depression caused by the blockage of high-affinity choline transporter (HChT) by hemicholinium-3 (HC-3), a condition that mimics a myasthenia-like condition. Methods: Rat diaphragm preparations were indirectly stimulated via the phrenic nerve trunk with 50-Hz frequency trains, each consisting of 500–750 supramaximal intensity pulses. The tension at the beginning (A) and at the end (B) of the tetanus was recorded and the ratio (R) B/A calculated. Results: Activation of A_2A and M₁ receptors with CGS21680 (CGS; 2 nmol/L) and McN-A-343c (McN; 3 μmol/L) increased R values. Similar facilitatory effects were obtained with forskolin (FSK; 3 μmol/L) and phorbol 12-myristate 13-acetate (PMA; 10 μmol/L), which activate adenylate cyclase and protein kinase C respectively. HC-3 (4 μmol/L) decreased transmitter exocytosis measured by real-time videomicroscopy with the FM4-64 fluorescent dye and prevented the facilitation of neuromuscular transmission caused by CGS, McN, and FSK, with a minor effect on PMA. The acetylcholinesterase inhibitor, neostigmine (NEO; 0.5 μmol/L), also decreased transmitter exocytosis. The paradoxical neuromuscular tetanic fade caused by NEO (0.5 μmol/L) was also prevented by HC-3 (4 μmol/L) and might result from the rundown of the positive feedback mechanism operated by neuronal nicotinic receptors (blocked by hexamethonium, 120 μmol/L). Conclusion: Data suggest that the recovery of tetanic neuromuscular facilitation by adenosine A_2A and M₁ receptors is highly dependent on HChT activity and may be weakened in myasthenic patients when HChT is inoperative.

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Wearable Systems of Reconfigurable Microneedle Electrode Array for Subcutaneous Multiplexed Recording of Myoelectric and Electrochemical Signals

Liu,

Yao,

et al. 2024

Advanced Science

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The real‐time monitoring of in vivo electrophysiological and biochemical signals provides critical insights into the activities of tissues and organs. As the activity and metabolic state of different sites in the muscle vary, multichannel detection is necessary to capture the functional state of the whole muscle, yet the access to the bio‐information in subcutaneous space remained challenging. This work reports the development of a reconfigurable microneedle electrode array integrated system designed to achieve painless and minimally invasive monitoring of subcutaneous electromyogram (EMG), oxygen species, and pH through an array of thumbtack‐shaped microneedle (TSMN) electrode. By assembling discrete TSMNs into an array, the system enables multi‐parameter detection with single microneedle resolution. The PEDOT: PSS layer is electrochemically deposited on the TSMNs, enhancing their signal‐sensing capabilities and electrochemical properties. Additionally, the design of the pogo pin interface ensures reliable signal transmission and stable device performance, while allowing flexible replacement of the TSMNs, which enhances system maintainability and longevity. Validation experiments conducted on in vivo animal models demonstrate the system's capability in real‐time monitoring of muscle fatigue and indicators related to sciatic nerve injury. These results advance the development of wearable technologies for monitoring subcutaneous physiological and biochemical information for diagnosing neuromuscular disorders.

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The functional organization of motor nerve terminals

Cited by 62 publications

References 377 publications

NMJ-morph reveals principal components of synaptic morphology influencing structure–function relationships at the neuromuscular junction

NMJ-morph reveals principal components of synaptic morphology influencing structure–function relationships at the neuromuscular junction

Tetanic Facilitation of Neuromuscular Transmission by Adenosine A<sub>2A</sub> and Muscarinic M<sub>1</sub> Receptors is Dependent on the Uptake of Choline via High-Affinity Transporters

Wearable Systems of Reconfigurable Microneedle Electrode Array for Subcutaneous Multiplexed Recording of Myoelectric and Electrochemical Signals

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