Theoretical analysis of mechanisms of nerve impulse conduction along myelinated fiber after a functional change in the properties of individual nodes

It is shown in a mathematical model of a myelinated nerve fiber that the development of a local response in an inexcitable node plays an important role in the mechanism of the "jumping" of an action potential (AP) across the inexcitable node. In the absence of such a response (for example, in the case of a 1000-fold decrease in the maximum sodium permeability, _Na) in fibers with normal relations between the length of the internodal segment (L) and its diameter (D) (L/D>100), the conduction is blocked. It is possible only in fibers with relatively short internodal segments (L/D<90). With a decrease in the _Na in several nodes, the transmission of excitation from the first to the second altered node is of critical importance for propagation of the impulse. The conduction of an AP becomes decremental if in each of the altered nodes the AP acquires a gradual character, for example, in the case of acceleration of sodium inactivation through the rate constant _h.A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 3, pp. 316–324, May–June, 1971.     

Electrical signs of impulse conduction in spinal motoneurons

An analysis has been made of the electrical responses recorded on the surface and within the substance of the first sacral spinal segment when the contained motoneurons are excited by single and repeated antidromic ventral root volleys. A succession of negative deflections, designated in order of increasing latency m, i, b, d, has been found. Each of those deflections possesses some physiological property or properties to distinguish it from the remainder. Indicated by that fact is the conclusion that the successive deflections represent impulse conduction through successive parts of the motoneurons that differ in behavior, each from the others. Since the spinal cord constitutes a volume conductor the negative deflections are anteceded by a positive deflection at all points except that at which the axonal impulses first enter from the ventral root into the spinal cord. Frequently two or more negative deflections are recorded together in overlapping sequence, but for each deflection a region can be found in which the onset of that deflection marks the transition from prodromal positivity to negativity. Deflection m is characteristic of axonal spikes. Latent period is in keeping with known axonal conduction velocity. Refractory period is brief. The response represented by m is highly resistant to asphyxia. Maximal along the line of ventral root attachment and attenuating sharply therefrom, deflection m can be attributed only to axonal impulse conduction. Deflection i is encountered only within the cord, and is always associated with a deflection b. The i,b complex is recordable at loci immediately dorsal to regions from which m is recorded, and immediately ventral to points from which b is recorded in isolation from i. Except for its great sensitivity to asphyxia, deflection i has properties in common with those of m, but very different from those of b or d. To judge by properties i represents continuing axonal impulse conduction into a region, however, that is readily depolarized by asphyxia. Deflection b possesses a unique configuration in that the ascending limb is sloped progressively to the right indicating a sharp decrease in velocity of the antidromic impulses penetrating the b segment. A second antidromic volley will not conduct from i segment to b segment of the motoneurons unless separated from the first by nearly 1 msec. longer than is necessary for restimulation of axons. This value accords with somatic refractoriness determined by other means. Together with spatial considerations, the fact suggests that b represents antidromic invasion of cell bodies. Deflection d is ubiquitous, but in recordings from regions dorsal and lateral to the ventral horn, wherein an electrode is close to dendrites, but remote from other segments of motoneurons, d is the initial negative deflection. In latency d is variable to a degree that demands that it represent slow conduction through rather elongated structures. When associated with deflection b, deflection d may arise from the peak of b with the only notable discontinuity provided by the characteristically sloped rising phase of b. Deflection d records the occupation by antidromic impulses of the dendrites. Once dendrites have conducted a volley they will not again do so fully for some 120 msec. Embracing the several deflections, recorded impulse negativity in the motoneurons may endure for nearly 5 msec. When the axonal deflection m is recorded with minimal interference from somatic currents, it is followed by a reversal of sign to positivity that endures as long as impulse negativity can be traced elsewhere, demonstrating the existence of current flow from axons to somata as the latter are occupied by impulses. Note is taken of the fact that impulse conduction through motoneurons is followed by an interval, measurable to some 120 msec., during which after-currents flow. These currents denote the existence in parts of the intramedullary motoneurons of after-potentials the courses of which must differ in different parts of the neurons, otherwise nothing would be recorded. The location of sources and sinks is such as to indicate that a major fraction of the current flows between axons and somata. For approximately 45 msec. the direction of flow is from dendrites to axons. Thereafter, and for the remaining measurable duration, flow is from axons to dendrites.     

Modification by temperature of conduction and ganglionic transmission in the gastropod nervous system

The pedal ganglia of the terrestrial gastropod Ariolimax contain junctions between nerve fibers which are shown to be preferential points of fatigue and which exhibit facilitation (summation) of preganglionic impulses to produce a postganglionic spike. These characteristics in conjunction with others previously reported (reversible susceptibility to nicotine, convergence of preganglionic impulses, and inhibition of transmission through setting up a refractory state in the postganglionic fiber) are considered sufficient to indicate synaptic transmission in the pedal ganglia. The mean conduction velocity of the fastest fibers in the pedal nerves is 0.52 meter per second for preganglionic and 0.50 meter per second for postganglionic fibers at 7.56°C. The conduction rates at 21.76°C. are respectively 0.80 meter per second and 0.83 meter per second. The mean ganglionic delay is 0.033 second at 7.56°C. and 0.019 second at 21.76°C. The mean Q₁₀'s for conduction velocity are thus 1.37 for preganglionic and 1.42 for postganglionic fibers. The mean Q₁₀ for ganglionic delay is 1.49. If the assumption is made that the Q₁₀ for ganglionic delay is that of a limiting reaction, this figure then represents a value below which the Q₁₀ for synaptic delay is statistically improbable.     

Inhibition of Impulse Activity in a Sensory Neuron by an Electrogenic Pump

The crayfish tonic stretch receptor neuron manifests three phenomena: (a) Impulse frequency in response to a depolarizing current decays exponentially to half the initial rate with a time constant of about 4 sec. (b) One or more extra impulses superimposed on steady activity result in a lengthening of the interspike interval immediately following the last extra impulse which is proportional to the number of extra impulses. However, above a "threshold' number of impulses the proportionality constant becomes abruptly larger. (c) Following trains of impulses, the resting potential of the cell is hyperpolarized by an amount proportional to impulse number. Such posttetanic hyperpolarization (PTH) decays approximately exponentially with a time constant of 11 sec, but this varies with membrane potential. These effects are attributed to the incremental increase of an inhibitory (hyperpolarizing) current with a long (relative to interspike interval) decay constant. We suggest that this inhibitory current is the result of increased electrogenic Na pumping stimulated by Na entering with each impulse. Evidence is presented that the three effects are reversibly inhibited by conditions which depress active Na transport: (a) Li substituted for Na in the bath; (b) application of strophanthidin; (c) K removal; (d) treatment with cyanide; (e) cooling. We conclude that a single process is responsible for the three responses described above and identify that process as electrogenic Na pumping. Our observations also indicate that electrogenic pumping contributes to this neuron's resting potential.     

The impact of internodal segmentation in biophysical nerve fiber models

Implementation of double cable models to simulate the behavior of myelinated peripheral nerve fibers requires defining a segmentation of the internode between successive nodes of Ranvier. The number of internodal segments is a model parameter that is not well agreed on, with values in the literature ranging from 1 to more than 500. Moreover, a lot of studies also lack a sensitivity study or a rationale behind the implementation used. In a model of a myelinated nerve fiber developed in our group, the segmentation scheme (i.e., the number of segments and their individual morphology) strongly influenced model outcomes such as action potential shape and velocity, stimulation threshold and absolute refractory period. In the present study these influences were investigated systematically in homogeneous neurons with different diameters. Uniformly segmented internodes were found to require several hundreds of segments (and associated computational power) to reach model outcomes differing by less than 1 % from the asymptotic value. In fact, in the majority of segmentation schemes the main determinant is not the number of segments, but the length λ of the internodal segments directly adjacent to the nodes of Ranvier. If λ is larger than approximately 10 μm, model outcomes for the tested fibers are almost independent of the total number of segments. Furthermore, λ can be optimized to enable models using just three segments per internode, to reach physiologically relevant model outcomes with limited computational resources. However, to study anatomical or physiological details of the internode itself, an appropriately detailed segmentation scheme is crucial.     

The nerve impulse in the axon — a new theory

The Classical Theory of function in the nervous system postulates that the nerve impulse is the result of a sequential reversal of the membrane potential due to an increased permeability of the membrane, first to sodium ions, then to potassium ions. The new theory presents a bio-physical model which depicts the nerve impulse as an event involving the motions of electrons and waves, and their interactions with sodium and potassium atoms and ions. The velocity of the nerve impulse (the most important parameter of nerve function) is determined by the product of two constants: c = the speed of light, which is a constant for all nerves; k =a constant for each nerve and is believed to be a specific property of nerve matter related in some way to the atomic process. The theory proposes that the nerve impulse in the axon is dualistic in nature (particles and waves play equally significant roles). The dualistic nature accounts for the three most fundamental characteristics of conduction of the nerve impulse: periodicity (conduction of a nerve impulse over long distances with constant velocity and form); non-summing (two nerve impulses cannot be in the same place at the same time); quantum nature of each nerve impulse — i.e., the unit message of the nerve impulse is an indivisible unit.     

Changes in interspike interval during propagation: Quantitative description

The intervals between nerve impulses can change substantially during propagation because of conduction velocity aftereffects of previous impulse activity. Effects of such changes on interval histograms and on statistical parameters of spike trains were evaluated for Poisson spike trains and for trains generated by a clock with added random delays. The distribution of short intervals was significantly changed during propagation for these spike trains. Substantial changes in serial correlation coefficients were found in trains with certain initial interval distributions. The relevance of these effects to neural coding is discussed.     

In Vivo Studies on Fast and Slow Muscle Fibers in Cat Extraocular Muscles

In anesthetized in vivo preparations, responses of two types of extraocular muscle fibers have been studied. The small, multiply innervated slow fibers have been shown to be capable of producing propagated impulses, and thus have been labeled slow multi-innervated twitch fibers. Fast and slow multi-innervated twitch fibers are distinguished by impulse conduction velocities, by ranges of membrane potentials, by amplitudes and frequencies of the miniature end plate potentials, by responses to the intravenous administration of succinylcholine, by the frequency of stimulation required for fused tetanus, and by the velocities of conduction of the nerve fibers innervating each of the muscle fiber types.     

Equilibria of frog nerve with different external concentrations of sodium ions

Using the ability of the nerve fibers to conduct impulses as indicator of changes in the concentration of sodium ions in the interstitial spaces of nerve an evaluation has been made of the diffusion constant of sodium ions. The calculated minimal value (0.62 x 10(-4) cm.(2)/min.) undoubtedly is much too low; nevertheless, it is still so high that as a rule the diffusion of sodium ions is far more rapid than the establishment of excitability changes; therefore, diffusion times need not be taken into account in the interpretation of ordinary experiments. By measurements of the changes in the longitudinal conductivity of nerve which result from changes in the external concentration of sodium chloride an evaluation has been made of the diffusion constant of sodium chloride in the interstitial spaces of nerve. A minimal value for this constant is 1.4 x 10(-4) cm.(2)/min. The evidence presented would be compatible with the assumption that the permeability of the connective tissue sheath for sodium ions decreases slightly after the concentration of sodium ions in the interstitial spaces of the nerve has become negligible; the evidence, however, shows that changes in the permeability of the sheath cannot play a significant role in determining the temporal courses of the development of inexcitability in a sodium-free medium and of the restoration of excitability by added sodium ions. If a decrease in the permeability of the sheath should take place in a sodium-free medium, the change would be small and would occur after the nerve fibers have become inexcitable; on the other hand the action of a moderate concentration of sodium ions would be sufficient to restore the permeability of the sheath. As measured by the recovery by A fibers of the ability to conduct impulses the restoration by 0.1 N sodium ions of nerve that has been deprived of sodium for 15 to 20 hours, i.e. for several hours after the nerve fibers have become inexcitable, begins after a significant delay, since no A fiber begins to conduct impulses in less than 8 or 10 minutes. The delay is referable to the fact that, before the A fibers can regain the ability to conduct impulses, those changes in their properties have to be reversed, which have taken place in the absence of sodium ions. Usually within 1 minute after sodium ions are made available to the nerve the polarizability of the membrane by the anodal current begins to increase; the A fibers soon begin to produce unconducted impulses in response to the break of the anodal current; then, they produce unconducted impulses in response to the closure of the cathodal current, and finally they become able to conduct impulses, although at a markedly reduced speed. The C fibers, that become inexcitable in a sodium-free medium later than the A fibers, begin to conduct impulses within 1 minute or 2 after 0.1 N sodium ions are made available to the nerve. Treatment of a nerve, that has been kept in a sodium-free medium, for 15 to 20 hours, with a moderate concentration of sodium ions (0.015, 0.02 N), acting for 1 hour or 2, is not sufficient to restore the ability to conduct impulses to more than a few A fibers, but it produces in a relatively large number of fibers a partial restoration, so that when the concentration of sodium ions outside the epineurium is increased by 0.005 or 0.01 N a significant number of A fibers begin to conduct impulses within less than 5 seconds. Initially the recovery progresses with great rapidity, but after a small number of minutes the height of the conducted spike remains practically stationary. Increase of the external concentration of sodium ions by a small amount again causes a rapid enhancement of the recovery, but once more, after a few minutes the height of the spike remains practically stationary, etc. A subnormal concentration of sodium ions may restore to all the A fibers the ability to conduct impulses, but only 0.1 N sodium ions are able to produce a complete restoration of the speed of conduction, and only after they have been allowed to act for a considerable period of time. The ability of all the C fibers to conduct impulses may be restored by relatively small concentrations of sodium ions, 0.02 to 0.025 N. Nerve fibers that have become inexcitable in a sodium-free medium and have been restored by sodium ions are far more sensitive to the effect of the lack of sodium than the fibers of untreated nerve. Repeated removal and addition of sodium ions may bring the nerve fibers, especially those of spinal roots, to a state in which the sensitivity to the lack of sodium is exceedingly great; spinal root fibers may then begin to become inexcitable in a sodium-free medium within a few seconds. Treatment of the nerve with 0.1 N sodium ions for 1 hour or 2 is sufficient to bring about a marked increase in the resistance to the lack of sodium. On the other hand keeping a nerve in Ringer's solution or in the presence of 0.04 N sodium ions does not produce a readily detectable increase in the sensitivity to the lack of sodium. Even the resistance of nerve kept in the presence of 0.025 N sodium ions for 23 hours is very high, since after 2 hours in a sodium-free medium more than two-thirds of the initially conducting fibers will be able to conduct impulses. Frog nerve reaches different states of equilibrium with different external concentrations of sodium ions. The states are characterized by the degree of effectiveness of the nerve reaction, the speed of conduction of impulses, and the number of conducting fibers. Approximately the same equilibrium state may be reached by (a) leaving the nerve for 20 to 24 hours in the presence of a subnormal concentration of sodium ions and (b) by leaving the nerve in a sodium-free medium for 15 to 20 hours, restoring it with 0.1 N sodium ions acting for a short period of time, rendering it inexcitable again in a sodium-free medium, and finally restoring it with a moderate concentration of sodium ions. If, however, the nerve that has been kept in a sodium-free medium for 15 to 20 hours is restored directly by a moderate concentration of sodium ions the state will not be reached, at least not for several hours, which corresponds to equilibrium with that concentration. The role of sodium in nerve physiology is discussed. Sodium participates in at least four processes, (a) The regulation of the concentration of water outside the nerve fibers; (b) the regulation of the total value of the membrane potential; (c) the production of the nerve impulse, and (d) the establishment of the nerve reaction. In so far as processes (c) and (d) are concerned only the sodium present inside the nerve fibers plays a role; the presence of sodium ions outside the nerve fibers is important only because in the absence of interstitial sodium ions the nerve fibers lose a part of their internal sodium content. The nerve impulse and the nerve reaction may be produced for long periods of time after the concentration of sodium ions outside the nerve fibers has become negligible. A working hypothesis is put forward according to which the internal sodium content and the interstitial concentration of sodium ions are in equilibrium in so far as a different internal sodium content corresponds to each interstitial concentration. The properties of the nerve fibers are determined by the internal sodium content. The change in properties, i.e. in the state of the nerve fibers, results from processes that take place inside the nerve fibers after the interstitial concentration of sodium ions and consequently also the internal sodium content have been changed.     

Conduction in bundles of demyelinated nerve fibers: computer simulation

This study presents a model of action potential propagation in bundles of myelinated nerve fibers. The model combines the single-cable formulation of Goldman and Albus (1967) with a basic representation of the ephaptic interaction among the fibers. We analyze first the behavior of the conduction velocity (CV) under the change of the various conductance parameters and temperature. The main parameter influencing the CV is the fast sodium conductance, and the dependence of CV on the temperature is linear up to 30 degrees C. The increase of myelin thickness above its normal value (5 microm) gives a slight increase in CV. The CV of the single fiber decreases monotonically with the disruption of myelin, but the breakdown is abrupt. There is always conduction until the thickness is larger than 2% of its original value, at which with at this point a sharp transition of CV to zero occurs. Also, the increase of temperature can block conduction. At 5% of the original thickness there is still spike propagation, but an increase of 2 degrees C causes conduction block. These results are consistent with clinical observations. Computer simulations are performed to show how the CV is affected by local damage to the myelin sheath, temperature alterations, and increased ephaptic coupling (i.e., coupling of electrical origin due to the electric neutrality of all the nerve) in the case of fiber bundles. The ephaptic interaction is included in the model. Synchronous impulse transmission and the formation of "condensed" pulse states are found. Electric impulses with a delay of 0.5 ms are presented to the system, and the numerical results show that, for increasing coupling, the impulses tend to adjust their speed and become synchronized. Other interesting phenomena are that spurious spikes are likely to be generated when ephaptic interaction is raised and that damaged axons suffering conduction block can be brought into conduction by the normal functioning fibers surrounding them. This is seen also in the case of a large number of fibers (N=500). When all the fibers are stimulated simultaneously, the conduction velocity is found to be strongly dependent on the level of ephaptic coupling and a sensible reduction is observed with respect to the propagation along an isolated axon even for low coupling level. As in the case of three fibers, spikes tend to lock and form collective impulses that propagate slowly in the nerve. On the other hand, if only 10% of fibers are stimulated by an external input, the conduction velocity is only 2% less than that along a single axon. We found a threshold value for the ephaptic coupling such that for lower values it is impossible to recruit the damaged fibers into conduction, for values of the coupling equal to this threshold only one fiber can be restored by the nondamaged fibers, and for values larger than the threshold an increasing number of fibers can return to normal functioning. We get values of the ephaptic coupling such that 25% of axons can be damaged without change of the collective conduction.     

Studies on the Distribution of Factor I and Acetylcholine in Crustacean Peripheral Nerve

Extracts of whole nerve (chelipeds of Cancer magister) cause inhibition of impulse generation of the crayfish stretch receptor preparation, similar to that produced by gamma-aminobutyric acid (GABA). This is not found with extracts containing only sensory or sensory and motor fibers. Extracts of inhibitory fibers inhibit the stretch receptor discharge—indicating an inhibitory action equivalent to that of up to 30,000 micrograms of GABA per gm. wet weight of inhibitor fiber. This high value is taken as an indication that the inhibitory substance in crab inhibitory fibers is not identical with gamma-aminobutyric acid. Whole nerves were found to contain 1.7 to 6.7 µg. acetylcholine per gm. nerve tissue (clam ventricle and frog rectus abdominis muscle). No acetylcholine could be detected in extracts of motor and inhibitory fibers. The acetylcholine content of sensory fibers can account for the acetylcholine activity of whole nerve extract. It is concluded that the factor I of crustacean nerve is an exclusive property of the inhibitory fibers. The results support the assumption that factor I is the transmitter substance of inhibitory neurons in these animals. The absence of acetylcholine in motor fibers indicates that this substance does not function as a transmitter of motor impulses in Crustacea, and explains the previously observed failure of the substance to elicit motor responses in these animals. The function of acetylcholine in sensory fibers is not yet clarified.     

A mathematical model of a myelinated nerve fiber for analysis of impulse conduction mechanisms during the relative refractory period

It was shown by means of a mathematical model of a myelinated nerve fiber (Frankenhaeuser — Huxley) that an increase in threshold and decrease in the amplitude of the action potential (AP) during the relative refractory period are due mainly to sodium inactivation. The contribution of increased potassium permeability to these changes is small, for the chief component of the outgoing ionic current in the node of Ranvier is not the potassium current, but the leak current. Given the ratio between these currents the increase in threshold and graduation of the action potential in the node membrane are less marked than in the membrane of the squid giant axon. At the beginning of the relative refractory period the AP evoked by strong stimulation is conducted only to the next node. Later in the refractory period impulses are conducted incrementally, and the threshold for the spreading impulse is higher than the threshold for spike excitation in the stimulated node. Delay in impulse conduction between refractory nodes leads to the formation of a retrograde depolarization wave. The reasons for differences in the mechanisms of impulse conduction along unmyelinated and myelinated refractory fibers are discussed.Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 4, No. 2, pp. 201–207, March–April, 1972.     

Maintained activity in the cat''s retina in light and darkness

Nervous activity has been recorded from the unopened eye of decerebrate cats. Recordings were made with metal electrodes or with small micropipettes from ganglion cells or nerve fibers. Continuous maintained discharges were seen in all ganglion cells during steady illumination of their receptive fields, as well as in complete darkness. Possible artefacts, such as electrode pressure, abnormal circulation, anesthetic, and several other factors have been excluded as the source of the maintained discharge. Visual stimuli are therefore transmitted by modulating the ever present background activity. Discharge frequencies were measured following changes of retinal illumination. No consistent patterns of frequency change were found. The maintained discharge frequency may be permanently increased or decreased, or may remain practically unchanged by altering the steady level of illumination. In addition, there were often transient frequency changes during the first 5 to 10 minutes after changing illumination, before a final steady rate was established. A statistical analysis of the impulse intervals of the maintained discharge showed: (a) the intervals were distributed according to the gamma distribution (Pearson's type III), (b) the first serial correlation coefficient of the intervals was between –0.10 and –0.24, with a mean value of –0.17, which is significantly different from zero, (c) the higher order serial correlation coefficients were not significantly different from zero. Thus the firing probability at any time depends on the times of occurrence of the two preceding impulses only, and in such a way as to indicate that each impulse is followed by a transient depression of excitability that outlasts the following impulse. The possible sites at which spontaneous or maintained activity may originate in the retina are discussed.     

Fenestration in the myelin sheath of nerve fibers of the shrimp: A novel node of excitation for saltatory conduction

Giant nerve fibers of the shrimp family Penaeidae conduct impulses at the velocity highest among all animal species (∼210 m/s; highest in mammals = 120 m/s). We examined these giant and other small nerve fibers morphologically using a differential interference contrast microscope as well as an electron microscope, and found a very specialized form of excitable membrane that functions as a node for saltatory conduction of the impulse. This node appeared under the light microscope as a characteristic pattern of concentrically aligned rings in a very small spot of the myelin sheath. The diameter of the innermost ring of the node was about 5 μm, and the distance between these nodes was as long as 12 mm. Via an electron microscope, these nodes were characterized by a complete lack of the myelin sheath, forming a fenestration that has a tight junction with an axonal membrane. Voltage clamp measurements by a sucrose gap technique demonstrated that the axonal membrane at these fenestration nodes is exclusively excitable and that the large submyelinic space is a unique conductive pathway for loop currents for saltatory conduction through such fenestration nodes. © 1996 John Wiley & Sons, Inc.     

Effects of heating and cooling on nerve terminal impulses recorded from cold-sensitive receptors in the guinea-pig cornea

An in vitro preparation of the guinea-pig cornea was used to study the effects of changing temperature on nerve terminal impulses recorded extracellularly from cold-sensitive receptors. At a stable holding temperature (31-32.5 degrees C), cold receptors had an ongoing periodic discharge of nerve terminal impulses. This activity decreased or ceased with heating and increased with cooling. Reducing the rate of temperature change reduced the respective effects of heating and cooling on nerve terminal impulse frequency. In addition to changes in the frequency of activity, nerve terminal impulse shape also changed with heating and cooling. At the same ambient temperature, nerve terminal impulses were larger in amplitude and faster in time course during heating than those recorded during cooling. The magnitude of these effects of heating and cooling on nerve terminal impulse shape was reduced if the rate of temperature change was slowed. At 29, 31.5, and 35 degrees C, a train of 50 electrical stimuli delivered to the ciliary nerves at 10-40 Hz produced a progressive increase in the amplitude of successive nerve terminal impulses evoked during the train. Therefore, it is unlikely that the reduction in nerve terminal impulse amplitude observed during cooling is due to the activity-dependent changes in the nerve terminal produced by the concomitant increase in impulse frequency. Instead, the differences in nerve terminal impulse shape observed at the same ambient temperature during heating and cooling may reflect changes in the membrane potential of the nerve terminal associated with thermal transduction.     

Afferent activity in thin myelinated and unmyelinated cutaneous nerve fibers during mechanical stimulation of skin receptors

Afferent activity in thin myelinated and unmyelinated cutaneous nerve fibers was analyzed by an impulse collision method and by methods improving the signal-to-noise ratio in the record of the antidromic action potential. The following groups were distinguished among the thin myelinated and unmyelinated nerve fibers on the basis of the results of investigation of conduction velocities, thresholds of electrical excitation, and response to mechanical stimulation: A ₁ (conduction velocity 30-14 m/sec) — a relatively larger number of these fibers conducts excitation in response to weak mechanical stimulation; A ₂ (14–4.0 m/sec) — the receptors of these fibers are more easily excited by a strong stimulus; a group of "mixed" fibers, containing myelinated and unmyelinated nerve fibers (4–2 m/sec), conducting excitation in response to both types of mechanical stimulation; C₁ (2.0–1.0 m/sec) — a fairly large number of these unmyelinated fibers conducts impulses in response to weak mechanical stimulation; C₂ (1.0–0.15 m/sec) the majority of fibers of this group is connected with receptors requiring strong mechanical stimulation for their excitation.Research Institute of Applied Mathematics and Cybernetics, N. I. Lobachevskii State University, Gor'kii. Translated from Neirofiziologiya, Vol. 8, No. 1, pp. 67–75, January–February, 1976.     

X-ray effects on single nerve fibers

Electrophysiological responses of median and lateral giant nerve fibers of the earthworm were recorded during exposure, in vitro, to x-rays. In response to external stimulation, during x-irradiation, these nerve fibers showed initially an increase in conduction velocity, a rise in spike amplitude, a decrease in relative refractory period, and an increase in sensitivity. These responses represent an enhancement of activity, attributable to bombardment with x-rays, rarely found in other biological systems. They were followed by deterioration of activity and eventual block, representative of the lethal action of x-rays, commonly observed in other biological systems. Several properties of the enhancement of activity were noted: The time at which maximum activity of one factor occurred did not coincide with the time at which the maxima of other activities occurred; spike amplitude, for example, was observed to increase while conduction velocity had already reached its maximum and was rapidly declining. The energy supplied by bombardment with x-rays did not act synergistically during the time of the enhanced response; that is, concomitant irradiation was not necessary in order to produce the enhanced response, once the nerve had been altered by x-irradiation. Once the nerve was responding in an enhanced manner, cessation of irradiation for short periods of time had no effect on the response. The phenomenon was therefore due to an irreversible alteration of the nerve fiber itself.     

Changes in the duration of the electric response of single nerve fibers following repetitive stimulation

Single nerve fibers were isolated from the nerve innervating the sartorius or semitendinosus muscle of the toad (Bufo marinus). Single nerve fiber responses were recorded with three arrangements of the "bridge insulator" method. During stimulation at 50 to 150 pulses per second for 20 to 140 minutes the spike duration was progressively increased. After tetanization the spike duration usually continued to increase at a more rapid rate. Within 5 to 60 minutes further prolongation stopped and within 1 to 10 hours the spike duration was normal. The duration of the response of tetanized fibers was from 2.5 to more than 10 times the spike duration of untetanized fibers. Prolongation was observed in nerve fibers isolated from nerves tetanized in vivo.     

A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy

Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy.     

Low temperature painful stimulus alters brain wave pattern of transcutaneous electrical stimulus

The somatosensory evoked response recorded from the scalp over the somatosensory cortex was used to examine the interaction between painful cold and transcutaneous electrical stimuli delivered concomitantly. When a painful cold stimulus was applied to the palmar receptive field of the median nerve while that nerve was being stimulated with electrical pulses at the wrist, there was an augmentation of an early component of the somatosensory evoked response manifested by an increase in the amplitude of a wave segment in comparison with room temperature controls. This augmentation depended on there being normal conduction of nerve impulses in both the population of small and large peripheral nerve fibers as compared to a state in which conduction was blocked selectively by a local anesthetic or a pressure cuff in those small and large fibers, respectively. The augmentation was not found to be characteristic of an arousal phenomenon, but was localized to the somatosensory cortex. This might represent the effects of a non-specific thalamortical projection system on a specific one.