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Journal of Integrative Neuroscience  2018, Vol. 17 Issue (4): 355-363    DOI: 10.31083/j.jin.2018.04.0417
Research article Previous articles | Next articles
Theoretical predication of temperature effects at 20 ℃-42  on adaptive processes in simulated amyotrophic lateral sclerosis
D. I. Stephanova1, *(), A. Kossev1
1 Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bontchev Str. Bl 21, Sofia 1113, Bulgaria
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Abstract  

Strength-duration time constants, rheobase currents, and recovery cycles allow the nerve adaptive processes to single or pairs of depolarizing stimuli to be assessed. This study investigates the temperature dependence of these excitability indices of human motor nerve fibers with one of three increasingly-severe type of amyotrophic lateral sclerosis pathology, referred to as ALS1, ALS2, and ALS3. The temperature dependence of the excitability indices was investigated during hypothermia (≤25 ℃), hyperthermia (≥40 ℃), and in the physiological temperature range (30-37 ℃). Numerical solutions were computed using a temperature-dependent multi-layered model. Results showed the following trends: (i) while the strength-duration time constants gradually decreased with a temperature increase from 20 ℃ to 42 ℃, they were longer in the three ALS cases than those of the normal case; (ii) the reciprocally dependent strength-duration time constants and rheobase currents were more sensitive to hyperthermia, especially at 42oC, than at temperatures across the physiological range of 30-37 ℃; (iii) the shape of temperature-dependent recovery cycles was similar for both the normal and ALS1 cases; (iv) in the ALS2 case, each test stimulus applied at the end of 100 ms recovery cycle failed to initiate a second action potential during hypothermia at 20 ℃; and (v) in the ALS3 case during hypothermia, hyperthermia and across the physiological temperature range, each test stimulus applied beyond a given conditioning-test interval was blocked. This blockage was a result of the spontaneous action potential generation caused by the conditioning (first) stimulus. The changes obtained for the temperature-dependent strength-duration time constants, rheobase currents, and recovery cycles reflect nodal and internodal ion channel dysfunctions in the three amyotrophic lateral sclerosis cases. It is proposed that these excitability indices can be applied clinically as specific indicators for amyotrophic lateral sclerosis motor neuron disease.

Key words:  Temperature      myelinated axons      ALS      strength-duration time constant      rheobase current      recovery cycle      computational neuroscience     
Submitted:  14 September 2017      Accepted:  23 February 2018      Published:  15 November 2018     
*Corresponding Author(s):  D. I. Stephanova     E-mail:  dsteph@bio.bas.bg

Cite this article: 

D. I. Stephanova, A. Kossev. Theoretical predication of temperature effects at 20 ℃-42  on adaptive processes in simulated amyotrophic lateral sclerosis. Journal of Integrative Neuroscience, 2018, 17(4): 355-363.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2018.04.0417     OR     https://jin.imrpress.com/EN/Y2018/V17/I4/355

Fig. 1.  Comparison between the strength-duration curves (first column) and charge-duration curves (last column) in the normal (a), ALS1 (b), and ALS2 Comparison between the strength-duration curves (first column) and charge-duration curves (last column) in the normal (a), ALS1 (b), and ALS2 = ALS3 (c) cases of hypothermic myelinated human motor nerve fibre (20 o C and 25 o C) and hyperthermia (40 o C and 42 o C). The strength-duration curves almost superimpose in the ALS1 case at 20 o C and 25 o C, thus lower temperature only is given.

Fig. 2.  Comparison between the strength-duration curves (first column) and charge-duration curves (last column) in the normal (a), ALS1 (b), and ALS2 = ALS3 (c) cases of the myelinated human motor nerve fibre in the physiological temperature range (30 o C, 32 o C, 34 o C, and 37 o C). The strength-duration and charge-duration curves almost superimpose, thus lowest and highest temperatures only are given.

Fig. 3.  Comparison between the strength-duration time constants (first column) and rheobase currents (last column) for normal (hatched first bars, from left to the right), ALS1 (white second bars), and ALS2 = ALS3 (hatched last bars) cases in the panel figures for the temperature ranges of 20-42 o C (a) and 30-37 o C (b), respectively.

Fig. 4.  Comparison between the absolute recovery cycles in the normal (first column), ALS1 (second column), ALS2 (third column), and ALS3 (last column) cases. The recovery cycles are numbered from 1 to 6 and each consecutive number corresponds to 20 o C, 30 o C, 34 o C, 37 o C, 40 o C and 42 o C, respectively. The recovery cycles are given in the temperature ranges of 20-30 o C (first row), 34-37 o C (second row) and 40-42 o C (last row). The dotted curves and lines indicate the lower of the two temperatures. The horizontal lines indicate the control threshold current (i.e. suprathreshold current increased by 5% of threshold) of the conditioning stimulus. CT intervals are plotted on logarithmic x -axis scales.

Fig. 6.  Comparison between the normalized recovery cycles in the normal, ALS1, ALS2 and ALS3 cases. The recovery cycles are numbered from 1 to 6 and each consecutive number corresponds to 20 o C, 30 o C, 34 o C, 37 o C, 40 o C and 42 o C, respectively. For all cases, the y -axis is defined as 100 x ( I test - I cond ) / I cond (%), where I test (nA) is the threshold current of the test stimulus and I cond (nA) is the control threshold current (i.e., suprathreshold current increased by 5% of threshold) of the conditioning stimulus. CT intervals are plotted on logarithmic x -axis scales.

Fig. 6.  Temporal distributions of action potentials when the test stimulus is applied as a function of CT interval, corresponding to: CT = 99 ms for the normal, ALS1, and ALS2 cases and CT = 39 ms for the ALS3 case during hypothermia at 20 o C (first row); CT = 69 ms and CT = 79 ms for the normal, ALS1, ALS2 and ALS3 cases during hyperthermia at 40 o C (second row) and 42 o C (last row), respectively. The testing action potentials are compared with spontaneous axonal activity caused by the conditioning action potentials in the ALS2 case at 20 o C and in the ALS3 case (last column). The action potentials are presented at each node from the 7th to the 14th and at each internodal segment between them. However, these segments respond equally, as periodic fibre polarization is realized and an overlap of the potentials in the nodal and internodal segments is obtained.

Fig. 7.  Temporal distributions of action potentials when the test stimulus is applied as a function of the CT intervals, corresponding to: CT = 49 ms for the normal, ALS1, ALS2, and ALS3 cases in the physiological temperature range at 30 o C (first row), 34 o C (second row) and 37 o C (last row), respectively, except for the ALS3 case, where the CT = 55 ms at 37 o C. The testing potentials are compared with spontaneous axonal activities caused by the conditioning action potentials in the ALS3 case (last column). The action potentials are presented at each node from the 7th to the 14th and at each internodal segment between them. However, these segments respond equally, as periodic fibre polarization is realized and an overlap of the potentials in the nodal and internodal segments is obtained.

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