Analysis Of Compound Action Potentials Research Articles

Analysis of compound action potentials elicited with specific current stimulating pulses in an isolated rat sciatic nerve.

The ability to selectively stimulate Aα, Aβ-fibers and Aδ-fibers in an isolated rat sciatic nerve (SNR) was assessed. The stimulus used was a current, biphasic pulse with a quasitrapezoidal cathodic phase and rectangular anodic phase where parameters were systematically varied: intensity of the cathodic phase (ic); width of the cathodic phase (tc); width of the cathodic exponential decay (texp) and time constant of the exponential decay (τexp). A SNR was stimulated using a pair of hook electrodes while conduction velocity (CV) and compound action potentials (CAP) were measured at two sites along the SNR using another two pairs of electrodes. Results showed that the highest CAP1 (8.5-9 mV), shall be expected when parameters of the stimulus were within the following range: ic=3.8-4 mA, tc=350-400 μs and texp=330-440 μs. Results also showed that with ascending tc and texp, CV of the corresponding superficial region of the SNR was reduced in both, conduction velocity of CAP1 and conduction velocity of CAP2. It was concluded that action potentials (APs) were activated in the Aβ-fibers and Aδ-fibers along with a slight AP inhibition in the Aβ-fibers. The obtained results, could serve as a tool for developing multi-electrode systems that potentially enable fiber-type selective stimulation of nerve fibers.

A simplified empirical modeling of electrophysiological activity in a bundle of myelinated nerve fibers

In vivo or in vitro electrophysiological characterization is a standard procedure to know specific aspects of the sensory and motor fibers conduction. In this work we propose a simplified empirical modeling that can predict the electrical activity evocated in a nerve by different experimental conditions. This approach includes physical and chemical concepts about the generation and propagation of myelin fiber action potentials, volume conduction and medium bioelectric properties; this was implemented by using simple qualitative parameters. The validation included the qualitative analysis of compound action potentials (CAPs) obtained from frog sciatic nerve in different experimental conditions and CAPs recordings obtained from infraorbital nerve in rats. The results reveal an adequate model fit to the CAPs waveform experimentally obtained. The intuitive parameters used in our approach facilitate the implementation and results interpretation, at the same time that provides versatility and robustness.

Neurophysiological analytics for all! Free open-source software tools for documenting, analyzing, visualizing, and sharing using electronic notebooks.

Neurophysiology requires an extensive workflow of information analysis routines, which often includes incompatible proprietary software, introducing limitations based on financial costs, transfer of data between platforms, and the ability to share. An ecosystem of free open-source software exists to fill these gaps, including thousands of analysis and plotting packages written in Python and R, which can be implemented in a sharable and reproducible format, such as the Jupyter electronic notebook. This tool chain can largely replace current routines by importing data, producing analyses, and generating publication-quality graphics. An electronic notebook like Jupyter allows these analyses, along with documentation of procedures, to display locally or remotely in an internet browser, which can be saved as an HTML, PDF, or other file format for sharing with team members and the scientific community. The present report illustrates these methods using data from electrophysiological recordings of the musk shrew vagus-a model system to investigate gut-brain communication, for example, in cancer chemotherapy-induced emesis. We show methods for spike sorting (including statistical validation), spike train analysis, and analysis of compound action potentials in notebooks. Raw data and code are available from notebooks in data supplements or from an executable online version, which replicates all analyses without installing software-an implementation of reproducible research. This demonstrates the promise of combining disparate analyses into one platform, along with the ease of sharing this work. In an age of diverse, high-throughput computational workflows, this methodology can increase efficiency, transparency, and the collaborative potential of neurophysiological research.

Detrended fluctuation analysis of compound action potentials re-corded in the cutaneous nerves of diabetic rats

The electrophysiological alterations in nerves due to diabetes are classically studied in relation to their instantaneous frequency, conduction velocity and amplitude. However, analysis of amplitude variability may reflect the occurrence of feedback loop mechanisms that adjust the output as a function of its previous activity could indicate fractal dynamics. We assume that a peripheral neuropathy, such as that evoked by diabetes, the inability to maintain a steady flow of sensory information is reflected as a breakdown of the long range power-law correlation of CAP area fluctuation from cutaneous nerves. To test this, we first explored in normal rats whether fluctuations in the trial-to-trial CAP area showed a self-similar behavior or fractal structure by means of detrended fluctuations analysis (DFA), and Poincare plots. In addition, we determine whether such CAP fluctuations varied by diabetes induction. Results showed that CAP area fluctuation of SU nerves evoked in normal rats present a long term correlation and self-similar organization (fractal behavior) from trial to trial stimulation as evidenced by DFA of CAP areas. However, CAPs recorded in diabetic nerves exhibited significant reductions in area, larger duration and increased area variability and different Poincare plots than control nerves. The Hurst exponent value determined with the DFA method from a series of 2000 CAPs evoked in diabetic SU nerves was smaller than in control nerves. It is proposed that in cutaneous nerves of normal rats variability of the CAP area present a long term correlation and self-similar organization (fractal behavior), and reflect the ability to maintain a steady flow of sensory information through cutaneous nerves. Nevertheless, this is not the case for sural nerves of diabetic rats which is reflected as a breakdown of the long range power-law correlation of CAP area fluctuation. Nonlinear time series analysis of CAP area fluctuations is a valuable new insight tool that can be used for the study of alterations in transmission of sensory information in humans suffering diabetes or under other demyelination diseases.

Differential contribution of BDNF and NGF to long-term potentiation in the superior cervical ganglion of the rat

Synaptic transmission in the sympathetic nervous system is a plastic process modulated by different factors. We characterized the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) on basal transmission and ganglionic long-term potentiation (LTP) in the rat superior cervical ganglion. LTP was elicited by supramaximal tetanic stimulation (40 Hz, 3 s) of the sympathetic trunk and was quantified by measuring LTP decay time and LTP extent. Neurotrophins did not affect basal transmission, however, they differentially affected LTP. BDNF (200 ng/ml) increased LTP decay time and LTP extent 2.0-fold (p < 0.01). In contrast, NGF showed a dual effect: 200 ng/ml NGF reduced LTP decay time and LTP extent to 53% and to 32% of control value (p < 0.0001 and p < 0.02; respectively), whereas >350 ng/ml NGF significantly increased LTP decay time and LTP extent (p < 0.02). Digital analysis of compound action potentials suggests that neurotrophins could change the synchronization of unitary action potentials. Pharmacological data obtained in intact ganglia show that C2-ceramide produced a 2-fold enhancement in LTP, whereas tyrphostin AG879, an inhibitor of tyrosine kinase activity, reversed the NGF blockade and produced by itself an enhancement in LTP. In sliced ganglia we observed that an anti-TrkA antibody reversed the NGF-induced LTP blockade. Immunohistochemistry studies revealed that 83% of ganglionic neurons express TrkA, whereas 52% express p75 receptor, and 18% express TrkB receptor. We propose that p75 neurotrophin receptors and probably TrkB signaling enhance LTP, whereas TrkA signaling reduces it.

Contribution of Fast and Slow Conducting Myelinated Axons to Single-Peak Compound Action Potentials in Rat Spinal Cord White Matter Preparations

Unlike recordings derived from optic nerve or corpus callosum, compound action potentials (CAPs) recorded from rodent spinal cord white matter (WM) have a characteristic single-peak shape despite the heterogeneity of axonal populations. Using a double sucrose gap technique, we analyzed the CAPs recorded from dorsal, lateral, and ventral WM from mature rat spinal cord. The CAP decay was significantly prolonged with increasing stimulus intensities suggesting a recruitment of higher threshold, slower conducting axons. At 3.5 mm conduction distance, a hidden higher threshold, slower conducting component responsible for prolongation of CAP decay was uncovered in 22 of 25 of dorsal WM strips by analyzing the stimulus-response relationships and a normalization-subtraction procedure. This component had a peak conduction velocity (CV) of 5.0 ± 0.2 (SE) m/s as compared with 9.3 ± 0.5 m/s for the lower threshold peak (P < 0.0001). Oxygen-glucose deprivation (OGD), along with its known effects on CAP amplitude, significantly (P < 0.015) shortened the CAP decay. The hidden higher threshold, slower conducting component showed greater sensitivity to OGD compared with the lower threshold, faster conducting component, suggesting a differential sensitivity of axonal populations of spinal cord WM. At longer conduction distances and lower temperatures (9.8 mm, 22-24°C), the slower peak could be directly visualized in CAPs at higher stimulation intensities. A detailed analysis of single-peak CAPs to identify their fast and slow conducting components may be of particular importance for studies of axonal physiology and pathophysiology in small animals where the conduction distance is not sufficiently long to separate the CAP peaks.

Modular double sucrose gap apparatus for improved recording of compound action potentials from rat and mouse spinal cord white matter preparations

Compound action potential (CAP) recording is a powerful tool for studying the conduction properties and pharmacology of axons in multi-axonal preparations. The sucrose gap technique improves CAP recording by replacing the extracellular solution between the recording electrodes with a non-conductive sucrose solution to minimize extracellular shunting. The double sucrose gap (DSG), conferring similar advantages at the stimulation site, has been extensively used on guinea pig spinal cord white matter (WM) in vitro. Establishing the DSG methodology for WM preparations from smaller animals such as rats and mice is appealing due to their extensive use in basic and translationally oriented research. Here we describe a versatile modular DSG apparatus with rubber membrane separation of the compartments, suitable for WM strips from rat and mouse spinal cord. The small volumes of compartments (<0.1 ml) and the air-tight design allow perfusion rates of 0.5–1 ml/min with faster refreshment rates compared to commonly used 2–3 ml/min and larger compartments, providing economical usage of expensive pharmacological drugs. Our improved DSG design is particularly efficient for uncovering slower conducting, higher threshold CAP components, as demonstrated by recordings of C-wave (non-myelinated axons) in rat dorsal WM. In myelin-deficient Shiverer mice with genetically dysmyelinated axons, our DSG apparatus recordings revealed a multi-peak C-wave without preceding faster components. The improved stimulation and recording with our DSG apparatus, lowering the range of required stimulus intensities and reducing the artifact interference with recorded CAPs provide for critical technical advantages that allow for more detailed analysis of CAPs in relatively short preparations.

Interactive program for spectral and area analysis of compound action potentials of A-fiber and C-fiber

An interactive program was described to correct the baseline wandering of the compound action potentials (CAPs) of C-fiber, to calculate the area and the peak amplitude of CAPs, and to analyze their spectral distribution. Using this program, we found the optimal bandpass of the filter for recording CAPs to be from 10 Hz to 3 kHz.

Modulation of cochlear tuning by low-frequency sound

An intense, low-frequency tone (about 30 Hz) modulates the sensitivity of the inner ear to high-frequency stimulation. This modulation is correlated with the displacement of the basilar membrane. The findings suggest that the modulation may also affect cochlear tuning. We have investigated modulation of cochlear tuning by low-frequency sound in the guinea pig. Applying indirect methods of measurement (narrow-band analysis of compound action potentials and compound-action-potential tuning curves), the results suggest a shift of the excitation pattern along the basilar membrane towards higher-frequency areas. The shift occurred for both scala tympani and scala vestibuli displacement of the cochlear partition. Tuning curves, obtained from single units in the cochlear nerve, show sensitivity loss and a tip shift towards lower frequencies. This was also found for both scala tympani displacement and scala vestibuli displacement. The shift of the tip of the tuning curve towards lower frequencies corresponds to the inferred high-frequency shift of the excitation pattern. The relationship of these phenomena with the pathophysiology of Ménière's disease and with possible active mechanisms in cochlear transduction is discussed.

Narrow-band analysis of compound action potentials for several stimulus conditions in the guinea pig

Compound action potentials (AP) were recorded under various stimulus conditions in 31 guinea pigs. Stimulus attenuation, decrease of inter-stimulus interval, increase of the level of a continuous wide-band noise masker, and lowering of the animal's temperature all resulted in a drop of the AP amplitude and an increase in latency. A narrow-band analysis of the compound APs makes it possible to describe these AP changes in terms of the response behaviour of small cochlear regions according to their central frequencies. The results show that intensity-dependent changes in the AP parameters can be explained on the basis of the tuning properties of the auditory nerve fibres when the effect of the rise time of the toneburst stimulus is taken into account. Shortening of the inter-stimulus interval produces a complex interaction in terms of tone-burst frequency and the region along the cochlear partition that contributes dominantly to the AP. It is concluded that response contributions from the narrow bands with a central frequency near the toneburst frequency show the most adaptation. The change in amplitude for narrow-band responses under increased masking is similar to that for stimulus attenuation. It seems, however, that the underlying masking mechanism is more comparable to the adaptation mechanism. Cooling of the animal did not affect the sharpness of tuning. In all four recording situations there seems to be a decrease in the amount of synchronization of single-fibre responses as reflected in the width of narrow-band action potentials.

Short-term adaptation in single auditory nerve fibers: some poststimulatory effects.

Adaptation was produced by CF stimuli with durations ranging from 10 to 300 msec and intensities within 60 dB above a unit's threshold. The exposure caused a decrement in the response to a CF test tone applied after the termination of the adapting stimulus. In general, the poststimulatory decrement seemed to depend on the per‐stimulatory response to the adapting tone and not directly on the parameters of the adapting stimulus. For example, the decrement followed a saturating function of adapting sound intensity and was approximately proportional to the per‐stimulatory firing rate. At sufficiently high test intensities, the decrement was constant and independent of test intensity, and the saturation rate produced by the test tone was reduced. These poststimulatory results are qualitatively consistent with a model previously developed to describe some per‐stimulatory effects of short‐term adaptation [R. L. Smith and J. J. Zwislocki, Biol. Cybern. 17, 169–182 (1975)]. In both situations, a peripheral saturation appears to precede adaptation and limit the effects of high sound intensities.

Efferent fibers in the cervical sympathetic nerve influenced by light

Spontaneous electrical activity of single-fiber preparations isolated from the central stump of the cervical sympathetic nerve has been recorded, the discharge frequency of which was greatly modified by changing the intensity of light reaching the cat's eyes. These fibers showed the highest firing frequency during darkness and the lowest in light (sometimes complete inhibition) and a gradation of the response intermediate illumination values. Light stimulations ranged from 0 to 1500 lux. The close correlation between the discharge frequency of these fibers and at the light stimulus intensity suggested that the fibers originated from the Budge's ciliospinal center and were directed to the dilatator pupillae muscle. Analysis of these units, besides confirming the intervention of the sympathetic system in the development of the pupillary light reflex, corroborates the hypothesis of a larger participation of sympathetic nerves in the reflex response to darkness than in the response to light. The role of sympathetic nerves in the direct light reflex appeared larger than in the consensual one. The conduction velocities of the light-responsive components were in a range of 6 to 25 m/sec (usually between 10 and 15 m/sec) as determined by (i) the action potential evoked in the single-fiber preparations, (ii) the functional analysis of compound action potentials, and (iii) the use of the antidromic occlusion method on the whole cervical sympathetic nerve. Very small doses of Nembutal (5 mg/kg) greatly decreased the resting discharge of the sympathetic light-responsive fibers and completely abolished the response to darkness.