scholarly journals Interactions among diameter, myelination, and the Na/K pump affect axonal resilience to high-frequency spiking

2021 ◽  
Vol 118 (32) ◽  
pp. e2105795118
Author(s):  
Yunliang Zang ◽  
Eve Marder

Axons reliably conduct action potentials between neurons and/or other targets. Axons have widely variable diameters and can be myelinated or unmyelinated. Although the effect of these factors on propagation speed is well studied, how they constrain axonal resilience to high-frequency spiking is incompletely understood. Maximal firing frequencies range from ∼1 Hz to >300 Hz across neurons, but the process by which Na/K pumps counteract Na+ influx is slow, and the extent to which slow Na+ removal is compatible with high-frequency spiking is unclear. Modeling the process of Na+ removal shows that large-diameter axons are more resilient to high-frequency spikes than are small-diameter axons, because of their slow Na+ accumulation. In myelinated axons, the myelinated compartments between nodes of Ranvier act as a “reservoir” to slow Na+ accumulation and increase the reliability of axonal propagation. We now find that slowing the activation of K+ current can increase the Na+ influx rate, and the effect of minimizing the overlap between Na+ and K+ currents on spike propagation resilience depends on complex interactions among diameter, myelination, and the Na/K pump density. Our results suggest that, in neurons with different channel gating kinetic parameters, different strategies may be required to improve the reliability of axonal propagation.

2021 ◽  
Author(s):  
Yunliang Zang ◽  
Eve Marder

AbstractAxons reliably conduct action potentials between neurons and/or other targets. Axons have widely variable diameters and can be myelinated or unmyelinated. Although the effect of these factors on propagation speed is well studied, how they constrain axonal resilience to high frequency spiking is incompletely understood. Maximal firing frequencies range from ~ 1 Hz to > 300 Hz across neurons, but the process by which Na/K pumps counteract Na+ influx is slow, and it is unclear the extent to which slow Na+ removal is compatible with high frequency spiking. Modeling the process of Na+ removal in unmyelinated and myelinated axons shows that both increasing diameter and myelination slow down [Na+] accumulation and increase axonal resilience to high frequency spiking. Increasing pump density alleviates [Na+] accumulation, but can paradoxically reduce the resilience. We speculate that [Na+] accumulation may contribute to fatigue after continuous high frequency firing.SignificanceThe reliability of spike propagation in axons is determined by complex interactions between ionic currents, ion pumps and morphological properties. We use compartment-based modeling to uncover that interactions of diameter, myelination and the Na/K pump determine axonal resilience to high frequency spiking. The Na/K pump can play a double-edged sword role in affecting axonal excitability. Our findings suggest that slow sodium removal influences axonal resilience to high frequency spiking, and may also contribute to fatigue.


2020 ◽  
Vol 117 (45) ◽  
pp. 28102-28113 ◽  
Author(s):  
Takashi Baba ◽  
Alejandro Alvarez-Prats ◽  
Yeun Ju Kim ◽  
Daniel Abebe ◽  
Steve Wilson ◽  
...  

Better understanding myelination of peripheral nerves would benefit patients affected by peripheral neuropathies, including Charcot–Marie–Tooth disease. Little is known about the role the Golgi compartment plays in Schwann cell (SC) functions. Here, we studied the role of Golgi in myelination of peripheral nerves in mice through SC-specific genetic inactivation of phosphatidylinositol 4-kinase beta (PI4KB), a Golgi-associated lipid kinase. Sciatic nerves of such mice showed thinner myelin of large diameter axons and gross aberrations in myelin organization affecting the nodes of Ranvier, the Schmidt–Lanterman incisures, and Cajal bands. Nonmyelinating SCs showed a striking inability to engulf small diameter nerve fibers. SCs of mutant mice showed a distorted Golgi morphology and disappearance of OSBP at the cis-Golgi compartment, together with a complete loss of GOLPH3 from the entire Golgi. Accordingly, the cholesterol and sphingomyelin contents of sciatic nerves were greatly reduced and so was the number of caveolae observed in SCs. Although the conduction velocity of sciatic nerves of mutant mice showed an 80% decrease, the mice displayed only subtle impairment in their motor functions. Our analysis revealed that Golgi functions supported by PI4KB are critically important for proper myelination through control of lipid metabolism, protein glycosylation, and organization of microvilli in the nodes of Ranvier of peripheral nerves.


2000 ◽  
Vol 6 (S2) ◽  
pp. 866-867
Author(s):  
G. Sosinsky ◽  
T. Deerinck ◽  
R. Greco ◽  
M. Ellisman

Nodes of Ranvier are sites on myelinated axons where the insulating layers of myelin are interrupted. They represent an excellent example of a complex cellular structure that contains highly differentiated sub-regions. At these sites of cell-cell specialization, ion fluxes occur which are required for propagation of action potentials. Myelinated axons and their nodes of Ranvier represent an important evolutionary advance for vertebrates that permit very rapid propagation of action potentials without large increases in axonal diameter. This physiological achievement is based on adaptations at a molecular level resulting in an elegant cooperation between glial cells and the axons of neurons.The organization and sub-specialization of the molecular components of the node of Ranvier are complex but often inter-related. The nodal region of axons are enriched in several channel and pump proteins including the voltage-gated Na+ channel, Na+-K+ ATPase and a number of different K+ channel isotypes.


1998 ◽  
Vol 143 (1) ◽  
pp. 195-205 ◽  
Author(s):  
Gregory A. Elder ◽  
Victor L. Friedrich ◽  
Chulho Kang ◽  
Paolo Bosco ◽  
Andrei Gourov ◽  
...  

Neurofilaments (NFs) are prominent components of large myelinated axons. Previous studies have suggested that NF number as well as the phosphorylation state of the COOH-terminal tail of the heavy neurofilament (NF-H) subunit are major determinants of axonal caliber. We created NF-H knockout mice to assess the contribution of NF-H to the development of axon size as well as its effect on the amounts of low and mid-sized NF subunits (NF-L and NF-M respectively). Surprisingly, we found that NF-L levels were reduced only slightly whereas NF-M and tubulin proteins were unchanged in NF-H–null mice. However, the calibers of both large and small diameter myelinated axons were diminished in NF-H–null mice despite the fact that these mice showed only a slight decrease in NF density and that filaments in the mutant were most frequently spaced at the same interfilament distance found in control. Significantly, large diameter axons failed to develop in both the central and peripheral nervous systems. These results demonstrate directly that unlike losing the NF-L or NF-M subunits, loss of NF-H has only a slight effect on NF number in axons. Yet NF-H plays a major role in the development of large diameter axons.


1995 ◽  
Vol 74 (3) ◽  
pp. 1362-1366 ◽  
Author(s):  
J. A. Huwe ◽  
E. H. Peterson

1. We visualized the central axons of 32 vestibular afferents from the posterior canal by extracellular application of horseradish peroxidase, reconstructed them in three dimensions, and quantified their morphology. Here we compare the descending limbs of central axons that differ in parent axon diameter. 2. The brain stem distribution of descending limb terminals (collaterals and associated varicosities) varies systematically with parent axon diameter. Large-diameter afferents concentrate their terminals in rostral regions of the medial/descending nuclei. As axon diameter decreases, there is a significant shift of terminal concentration toward the caudal vestibular complex and adjacent brain stem. 3. Rostral and caudal regions of the medial/descending nuclei have different labyrinthine, cerebellar, intrinsic, commissural, and spinal connections; they are believed to play different roles in head movement control. Our data help clarify the functions of large- and small-diameter afferents by showing that they contribute differentially to rostral and caudal vestibular complex.


Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1015
Author(s):  
Antonio Bulum ◽  
Gordana Ivanac ◽  
Eugen Divjak ◽  
Iva Biondić Špoljar ◽  
Martina Džoić Dominković ◽  
...  

Shear wave elastography (SWE) is a type of ultrasound elastography with which the elastic properties of breast tissues can be quantitatively assessed. The purpose of this study was to determine the impact of different regions of interest (ROI) and lesion size on the performance of SWE in differentiating malignant breast lesions. The study included 150 female patients with histopathologically confirmed malignant breast lesions. Minimal (Emin), mean (Emean), maximal (Emax) elastic modulus and elasticity ratio (e-ratio) values were measured using a circular ROI size of 2, 4 and 6 mm diameters and the lesions were divided into large (diameter ≥ 15 mm) and small (diameter < 15 mm). Highest Emin, Emean and e-ratio values and lowest variability were observed when using the 2 mm ROI. Emax values did not differ between different ROI sizes. Larger lesions had significantly higher Emean and Emax values, but there was no difference in e-ratio values between lesions of different sizes. In conclusion, when measuring the Emin, Emean and e-ratio of malignant breast lesions using SWE the smallest possible ROI size should be used regardless of lesion size. ROI size has no impact on Emax values while lesion size has no impact on e-ratio values.


2013 ◽  
Vol 353-356 ◽  
pp. 459-462
Author(s):  
Ying Jie Zheng ◽  
Bin Fang ◽  
Lian Xiang Li

Pile tip absolute settlement curves and relative settlement curves of several working cases were analyzed. It is found that load-settlement curve characteristic related to the selection standard. The tip resistance initial stiffness of each case was analyzed. Results show that the small diameter pile has higher initial stiffness than large diameter pile, embedded depth has little influence on initial stiffness ratio, but increment of initial stiffness is linear with embedded depth growth.


1979 ◽  
Vol 78 (1) ◽  
pp. 121-136
Author(s):  
GERALD E. SILVEY ◽  
IAN S. WILSON

The syncarid crustacean Anaspides tasmaniae rapidly flexes its free thoracic and abdominal segments in response to tactile stimulation of its body. This response decrements but recovers in slightly more than one hour. The fast flexion is evoked by single action potentials in the lateral of two large diameter fibres (40 μm) which lie on either side of the cord. The lateral giant fibre is made up of fused axons of 11 neurones, one in each of the last 5 thoracic and 6 abdominal ganglia. The soma of each neurone lies contralateral to the axon. Its neurite crosses that of its counterpart in the commissure and gives out dendrites into the neuropile of each hemiganglion. The lateral giant neurone receives input from the whole body but fires in response only to input from the fourth thoracic segment posteriorly. Both fibres respond with tactile stimulation of only one side. Since neither current nor action potentials spread from one fibre to the other, afferents must synapse with both giant neurones. The close morphological and physiological similarities of the lateral giant neurone in Anaspides to that in the crayfish (Eucarida) suggest that the lateral giant system arose in the ancestor common to syncarids and eucarids, prior to the Carboniferous.


Author(s):  
E. Rehleckaya ◽  
A. Dymkov ◽  
L. Lazarets ◽  
A. Maltsev

Purpose: Install the influence of the «small diameter of the egg» on the living mass and the reproductive qualities of chickens of meat crosses and the quail of meat breeds.Materials and methods. The selection was carried out along egg production and mass of eggs and additionally on the average small diameter of 5 eggs by value of ≥0.5σ from the average for the herd, while the evaluation on the basis of the «small diameter of the egg» was carried out in chickens aged 238 days of life, quails — 70 days of life. Calculated the average for each female and the average for the herd. For further reproduction, chickens carrying eggs with a small egg diameter ≥0.5σ from the average for the herd. Studies were held in SibNIP on quail and on the courses.Results. In the initial period of the egg laying, the individual variability of the small diameter of the egg — more than 10% (in the future, the figure decreased). The close correlation rate of the small egg diameter in the first half of the egg laying with such at the end of the bird's operation period was revealed. It has been established that the large diameter of the egg has a positive reliable connection with a lively mass, but negative with egg production. The reliable correlation rate of the small diameter of the egg with a live weight at a 42-day age, as well as with the derivation of eggs. The inheritance coefficients of the small diameter of the egg are comparable to the inheritance coefficients of the mass of eggs and significantly exceed those for a large diameter of the egg. The selection according to the small diameter of the eggs by ≥0.5σ from the average for the herd led to the fact that the chickens of the experimental groups reliably exceeded the live weight in the SB level of 1.57%, in the line G8 — by 1.35%. The superiority of a lively mass of quail of experienced groups was more pronounced than that of the chickens: the Pharaoh breed — by 4.15%, the Texas white breed is 4.22%. In relation to the derivation of eggs, a similar trend was traced. The derivation of eggs in quails of experienced groups was more than 4.59–4.98%; Country, respectively, 4.57–5.22%. Egg production of females of comparable groups of both chickens and quail was almost on the same level, and the difference was unreliable.Conclusion. It was established that a new method of breeding the poultry of the meat direction of productivity allows without decreasing egg production to increase the living mass of chickens of meat crosses by 1.5%, rewinds of meat breeds — by 4%, the derivation of eggs, respectively, by 4–5%. The method is intended for early prediction of females productivity during breeding selection.


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