An Original Neural Info Coding Mode: Conductive Coding Of Rabbits' Saphenous Non-myelinated Fibers

The axon has been defined as a long neuronal process, which works like a cablebetween neurons, insuring the conduction of information from the cell body to thenerve terminal. By large numbers of fibers, ramifications and synapses, neurons arenot only connected with each other but also with their receptors, thus constituting acomplicated neural signal processing system.But, more and more experimental and theoretical evidences exhibit the necessityof reexamination of the functions of fibers, especially the functions of nonmyelinatednerve fibers(C-fibers). For example, C fibers show obvious activity-dependentaftereffects, which make the conduction velocity either a slow or a quick non-linearchange. Bunchy stimulation makes the interspike intervals (ISI) change obviously.Some fibers have propagation failures and reflected actions. These phenomena showthat a train or "code' of action potentials (AP) is not always transmitted faithfullyalong the axon; rather, axons have the ability to "integrate' recent changes inmembrane potentials. To understand the ability to integrate' and conductive coding offibers, three questions are to be answered: (1) How does ISI change during APpropagation? (2) Are these changes elicited in the process of AP propagations or in thespike electrogeneses? (3) What mechanisms are there for the conductive coding? Theresearch here is to study these questions and to provide evidence for theunconventional neural information coding mode.The study of the conductive coding during the course of AP propagating alongaxons and the ionic mechanisms is to be done with single fiber recording techniquesin rabbits" saphenous nerves and with changes of ISI during continuous repeating orstringing pulse stimulation, to analyze the effect of conduction velocity, distance andfiber membrane currents on ISI, which is to be validated through mathematic matrixto establish a "conductive coding" with essential experimental and theoreticalfoundations. Main results:Section 1 Repetitive continuous stimulation for changes in the ISI series1. During repetitive continuous stimulations, different type of C-fiber haddifferent form of discharge. 510 saphenous C-units were recorded by meansof single-fiber recording techniques. According to their different patterns ofinterspike interval (ISI) series induced by frequency-dependent propagationfailures during repeated electrical stimulations, the units were classified intothree types. Type 1 were tonic firing C-fibers, during the stimulation ISIseries remain obvious un-changes. Type 2 were intermittent failures ofC-fibers, intermittent periods of action potential conduction alternated withfailure. Type3 were irregular failures of C-fibers, during repetitivecontinuous stimulation the fiber had irregular propagation failure. In thepresent study of the totality of 510 units, 86 (16.9%) units were classified astonic firing C-fibers, 75 (14.7%) units were classified as intermittentfailures of C-fibers, and 349 (68.4%) units were classified as irregularfailure of C-fibers2. Activity-dependent conduction velocity changes of different type of fibersduring the stimulation were different. Tonic firing fibers have a average CVoff. 41+0.03m/s (n=20). During the stimulation at 20Hz for 50s, there wasno propagation failure occurred, CV decreased from 1.35m/s tol.05m/s.Intermittent failure fibers have a average CV of 0.84m/s (n=20). During therepetitive stimulating of the nerve, the CV dropped from 0.85m/s to 0.68m/s,failure then occurred. when CV rise form 0.68m/s to 0.72m/s, the blockrecovered. Irregular failures of fibers have an average CV of 1.01m/s (n=20). During the stimulation CV dropped from 1.01m/s to 0.83m/sec, failurethen occurred. The decline in conduction velocity before failure could bedescribed as an exponential drop, and then CV gradually stabilizedat0.83m/s.3. The number and character of impulses required to elicit propagation failuresat a C-fiber varied widely between irregular failures and the intermittentfailures of C-fibers. The scattered plot showed that ISis had a brief decreaseat the beginning of stimulation, coefficient of variation of this period kept dropping and greater than 0.02, we defined this decreasing period as phase 1.Then the ISI kept steady for a long time (about 20s at this example),coefficient of variation of this period kept less than 0.02, we defined thissteady period as phase 2, which is followed by a steep rise of ISI fluctuations.The profile of ISis scattered out with a trumpet-like end, coefficient ofvariation of this period kept rising and greater than 0.02. We defined thisflared period as phase3.4. This finding reflects the fact that ISI fluctuation and CV slowing are keyfactors to elicit propagation failures. For intermittent failures of C fibers, thethreshold of CV slowing was 6%. Once the CV slowing greater than 6%, theISI fluctuated acutely. When the CV slowing greater than 14%, theamplitude of ISI fluctuation was 3ms, then propagation failures occurred; forirregular failure C fibers, the threshold of CV slowing was 27%. Once theCV slowing greater than 27%, the ISI fluctuated acutely. When the CVslowing greater than 34.8%, the amplitude of ISI fluctuation was 1.7ms, thenpropagation failures occurred.5. Compare effects of average distances of 76±5mm on the propagation failuresof an average distance of 44.2±6mm (n=14). The resting CV of the twodistances was the same. But, during stander electrical stimulus at 20Hz, thetime to elicit conduction failures was 10.0±2.0 for longer distance, whereasit needed 17.5±3.0 for shorter distances. Stimulation in longer distancesshowed a slowing of CV of 16.1%±0.7 preceding conduction failures, that ofS2 was 27.01％±0.6. We can see that, the longer the distance, the easierpropagation failures to occur.6. Topically applying 4-APto C-fiber(10-40μM) produced a dose-dependentdecrease of conduction failures and decrease of the slop ofactivity-dependent CV slowing. 40 fibers were examined, 29 of themshowed the phenomena above, 8 of them showing contrary phenomena, 3 ofthem showing no response on 4-AP.7. Topically applying ZD7288 to C-fiber (5-20μM) produced a dose-dependentincrease of conduction failures and an increase of the slop ofactivity-dependent CV slowing. 40 fibers were examined, 22 of themshowed the phenomena above, 4 of them showed a light response toZD7288. 9 of them showd no response to ZD7288. in 5 of them, almost a complete suppression of firing was observed.8. The H-H neuron model was adopted to simulate the experimental results,activity-slowing, tonic firing, propagation failures, just as is discovered inour experiments, are simulated. The similarity of conduction phenomenabetween in the model and in the experiment is obvious.Section 2 string stimulations for changes in ISI series1. During bunchy stimulations, different types of C-fibers had different typesof discharges Electrical stimulation consisted of five pulses withinter-stimulus intervals of 20 or 50ms were applied every 200 or 500ms fora total of 200 five pulses. According to their different patterns of ISI series(especially the ISI of first AP and the second AP) during repeatedlyelectrically stimulations, the units were classified into three types. Type 1:During the stimulation of 20ms, ISI_1-2 increased from 20ms to 24ms, then,decreased to 8ms and kept 8ms for a long time. Type 2: During thestimulation of 50ms, ISI_1-2 decreased from 54ms to 48ms, then increased to51 ms, subsequently decrease to 50ms, then propagation failures occurred.Type 3: During the stimulation of 50ms, ISI_1-2 decreased from 54 ms to 52ms: then propagation failures occurred.2. Topically applying 4-AP to C-fibers significantly decreased the changes ofISis. 10μM 4-AP made the minimal ISI_1-2 increase from12.5ms to 14ms,and the steady value of ISI_1-2 increased from 15ms to 16.5ms. 20μM 4-APmade the minimal ISI_1-2 increase to 15ms, and the steady value of ISI_1-2increased to 18ms.3. Topically applying ZD7288 to C-fiber significantly increased the changesof ISIs. 5μM 4-AP made the minimal ISI_1-2 decrease from15ms to 13.5ms,and the steady value of ISI_1-2 decreased from 19.5ms to 18ms.4. Change of main intervals (the intervals between two stings) significantlychanged the ISIs. The inter-stimulation intervals are fixed to 20ms, thedifference of ISI became greater with shorter main-intervals. When themain interval was 400ms, the ISI_1-2 changed obviously, but others were notchanged, but when the main interval was 300ms or 200ms , the ISI_1-2changed obviously, others were not changed obviously too. Conclusion1. During repetitive stimulations, different types of C-fibers have differenttypes of discharges. According to their different patterns of interspikeinterval (ISI) series induced by frequency-dependent propagation failuresduring repeated electrical stimulations, the units were classified into threetypes.2. During quinary of electrical pulse, the ISI between action potentials(especially the 1Sis between the first and the second AP) had kinds ofchanges, for example, the model of increase-decrease, decrease-increase-decrease, keep decreasing.3. The changes of ISIs were because of activity-dependent CV slowing.4. During repetitive continuous stimulation, the ISI fluctuation, CV slowing,the form of propagation failure were all different between different type offibers, but the amplitude of conductions of velocity fluctuations were thesame, the amplitude of CV fluctuation was the indicator of propagationfailure.5. Distance action potentials passed had relations with the variances of ISI andpropagation failures. The longer the distance, the more the axons integratethe signal.6. 4-AP and ZD7288 can change the variance of ISI and propagation failures.They blocked currents which have relations with CV propagations, thus theability of axon's propagation were affected, so the variance of ISI andpropagation failures were changed.7. Axons have the ability to code signals which propagate along with it, thevariance of ISI and propagation failure is the form of conduction coding.