Activity Of Single Nerve Fibers Research Articles

A histamine-independent itch pathway is required for allergic ocular itch

Non-histaminergic TRPA1 neural pathway is required for the development of allergic ocular itch. Pharmacological inhibition of TRPA1 channel can lead to novel therapeutic strategies to treat ocular itch in severe allergic conjunctivitis.

Using the Horseshoe Crab, <em>Limulus Polyphemus</em>, in Vision Research

The American horseshoe crab, Limulus Polyphemus is one of the oldest creatures on earth, and the animal continues to play an indispensable role in biomedical research. Not only does their blood contain special cells that scientists use to detect bacteriotoxins in our medicines, but their eyes also contain a neural network that has provided much insight about physiological processes operating in our visual system, such as light adaptation and lateral inhibition. The horseshoe crab remains an attractive model for vision research because the animal is large and hardy for an invertebrate, its retinal neurons are big and easily accessible, its visual system is compact and extensively studied, and its visual behavior is well defined. Moreover, the structure and function of the eyes are modulated on a daily basis by a circadian clock in the animal s brain. In short, the visual system of horseshoe crabs is simple enough to be understood yet complex enough to be interesting.In this video we present three electrophysiological paradigms for investigating the neural basis of vision that can be performed in vivo with Limulus. They are electroretinogram recording, optic nerve recording, and intraretinal recording. Electroretinogram (ERG) recordings measure with a surface electrode the summed electrical response of all cells in the eye to a flash of light. They can be used to monitor the overall sensitivity of the eye for prolong periods of time. Optic nerve recordings measure the spiking activity of single nerve fibers with an extracellular microsuction electrode. They can be used to study visual messages conveyed from the eye to the brain as well as circadian-clock messages fed back from the brain to the eye. Intraretinal recordings measure with an intracellular microelectrode the voltage fluctuations induced by light in individual cells of the eye. They can be used to elucidate cellular mechanisms of retinal processing.

Impulse Activity in Corneal Sensory Nerve Fibers after Photorefractive Keratectomy

To evaluate the changes in spontaneous and stimulus-evoked nerve impulse activity of corneal polymodal and mechanonociceptor sensory fibers of the cornea after photorefractive keratectomy (PRK). A central corneal ablation 6 mm in diameter and 70 microm in depth was performed with an excimer laser in both eyes of three anesthetized cats, after removal of the corneal epithelium. Single nerve fiber activity was recorded in these animals 12 to 48 hours after surgery. Activity in corneal nerve fibers with receptive fields (RFs) within and/or close to the wound, as well as with RFs far from the lesioned area, was studied. Incidence and frequency of spontaneous discharges and nerve impulse firing responses to mechanical (Cochet-Bonet esthesiometer) and chemical (CO(2) gas pulses) stimuli were studied. The incidence of nociceptor fibers exhibiting ongoing activity (15/35 vs. 1/9) and the frequency of their spontaneous firing (0.25 +/- 0.09 impulses [imp]/s versus 0.08 +/- 0.08 imp/s) was higher in fibers with RFs within and/or bordering the wounded area than in those with RFs far away from the wound. Mechanical responsiveness of fibers with RFs within or nearby the ablated area was often reduced. In these fibers, CO(2) pulses evoked a lower-frequency impulse discharge (0.9 +/- 0.2 imp/s inside, 2.3 +/- 0.7 imp/s outside the wound). CO(2)-evoked discharges recorded from fibers innervating the intact wound border were similar to those recorded in corneal fibers of intact cats. The spontaneous impulse activity and the abnormal responsiveness shown by a part of the corneal nerve fibers innervating the injured cornea are presumably the neurophysiological substrate of the pain sensations experienced by human patients hours after PRK surgery.

Receptive properties of primary afferent fibres from rabbit pleura, in vitro

We investigated the physiological properties of mediastinal pleural primary afferent units by recording single nerve fibre activity from the phrenic nerve in an in vitro preparation of rabbit tissue. A total of 41 units with conduction velocities in the group III and IV range were examined for their responsiveness to mechanical, thermal and chemical stimuli. Most receptive fields were adjacent to the phrenic nerve-pericardiacophrenic artery complex. The thresholds to punctate mechanical stimulation (von Frey hairs) were widely scattered around a median of 5.4 mN; all fibres showed slowly adapting responses to mechanical stimulation. Heat sensitivity was observed in 7/41 units (17%), while 17/41 (41%) of the fibres exhibited a spurious transient excitation to strong and rapid cooling. Chemosensitivity was scarce with respect to capsaicin (7/33 (21%) of the units responding) but more common to CO2-saturated synthetic interstitial fluid (pH 6.1, 5/16 (31%) responding). The most effective stimulus was a mixture of bradykinin, serotonin, histamine and prostaglandin E2 ('inflammmatory soup') which evoked stimulus responses in 27/33 (82%) of the afferent fibres challenged. Sensitization to mechanical stimuli occurred in 5/41 (12%) of the units, following the application of heat or inflammatory mediators. The rabbit pleura appears as a tissue mainly innervated by multimodal mechano- and chemosensitive afferent units.

Serotonin-induced sensitisation of articular mechanonociceptors

Inflamed tissues produce a number of chemical mediators which can either directly excite peripheral mechanonociceptors or sensitise them to mechanical stimuli. It is well established, for example, that the responses of articular mechanonociceptors to mechanical stimuli are modified by prostaglandins in inflamed tissue since lysine acetylsalicylate can reverse mechanonociceptor sensitisation in models of joint inflammation [1-3]. Serotonin (5-hydroxytryptamine) is another potential modulator of articular mechanonociceptor sensitivity since it is algogenic when applied to the blister base [4], an effect which is mediated by the 5HT 3 receptor [5,6]. In the present study [7] we investigated whe ther serotonin excited or sensitised mechanonociceptors in a model of chronic joint inflammation. Extracellular recordings were made in urethane anaesthetised rats from the primary articulo-cutaneous ramus (PACR), a small nerve which innervates the tibio-tarsal joint [8]. In preparing the hind limb the cutaneous branches of this nerve are separated and most activity can be attributed to joint mechanonociceptors. Anatomical studies and measurements of conduction velocity have revealed that most nerve fibres contained in the PACR are unmyelinated or small unmyelinated fibres, indicating that they are either A-O or C-fibres. The activity of single nerve fibres was recorded either from the whole nerve or from fibres dissected from the nerve trunk. Measurements were made of spontaneous activity or activity evoked by graded indentation of the periarticular tissue with an electronically controlled mechanical probe. Drugs were administered through an indwelling catheter inserted retrogradely into the contralateral femoral artery until the tip was located at the iliac bifurcation of the

Spontaneous rhythmic activity of single nerve fibers of the cervical sympathetic nerve trunk of the rabbit

In experiments on rabbits anesthetized with urethane, we recorded spontaneous sympathetic activity of single nerve fibers. The activity was recorded from fine filaments dissected from the cervical sympathetic nerve trunk (CSNT). Conduction velocities in CSNT fibers and action-potential amplitude of single B-fibers were measured during recording of whole nerve trunk. Spectral analysis of the activity recorded was carried out. It was shown that unmyelinated CSNT fibers are under stronger baroreceptor control than myelinated fibers. Also, a periodic component of 2–3 Hz, noted by a number of authors after denervation of baroreceptors, was detected in intact animals along with a rhythm at the pulse rate. This component was found equally often in the activity of B- and C-fibers. Cross-correlation analysis of the simultaneously recorded activities of 24 pairs of CSNT single fibers was carried out. A correlation due to synchronization of the activities of pairs of fibers with a physiological rhythm (respiration, pulse) was found in five pairs. The correlation in one pair suggests the presence of a common excitatory synaptic input into two distinct preganglionic neurons.

Conduction studies in peripheral cat nerve using implanted electrodes: II. The effects of prolonged constriction on regeneration of crushed nerve fibers

Arrays of chronically implanted electrodes were used to examine the time course of elongation and maturation of peripheral nerve fibers in the cat after crush of the tibial nerve in the proximal calf. Regeneration after crush alone was compared with crush 5 mm proximal to a tight constriction of the nerve. Regeneration was monitored by the progression of excitability along the electrode arrays on the tibial and plantar nerves. The sensitivity was sufficient to record the averaged activity in single nerve fibers allowing detection of the earliest regeneration. The diameters of the fastest regenerating fibers were estimated from the conduction velocity proximal to the site of crush. Both after crush alone, and after crush constriction, small myelinated fibers regenerated in front of large fibers. The rate of elongation after crush alone was 3.2 mm/day, whereas it was slower (P less than 0.02) distal to crush + constriction (2.2 mm/day). In both lesions, the extrapolated delay to onset of regeneration was 8 days. In observations up to 300 days after crush, maturation was delayed or impaired by the constriction, and the compound nerve action potential had a smaller amplitude and a dispersed shape. Transverse sections of nerves after crush + constriction showed a diminished number of large and an increased number of small fibers compared with crush alone, possibly due to persistent branching of regenerated fibers. After both crush alone and crush + constriction, regenerated fibers had similar g ratios, suggesting that myelination developed fully in fibers of diminished diameters.

Peripheral mechanisms of somatic pain.

In the last two decades, considerable advances have been made in our understanding of the mechanisms of pain. Studies correlating subjective magnitude estimations of pain in man with activity in single nerve fibers in experimental animals, and microneurographic recordings in awake humans, have provided convincing evidence for the role of specific nociceptors and labelled lines for signalling pain sensation in the normal skin. The response properties of the different types of nociceptive afferents, both myelinated and unmyelinated, from skin, muscle, and joints make them ideal candidates for signalling pain sensations. Cutaneous inflammation from any cause results in hyperalgesia. Cutaneous hyperalgesia at the site of an injury, i.e., primary hyperalgesia, can be explained by sensitization of nociceptors. This sensitization is likely due to local release of chemical mediators in the inflamed area. The metabolites of arachidonic acid (eicasonoids) and bradykinin appear to play an important role in the sensitization of nociceptors. Similar inflammation-induced changes in response properties of fine articular afferents might explain the pain of acute arthritis. The neuropeptide substance P released from primary afferents may also play an important role in the pathogenesis of arthritis. The mechanism of hyperalgesia in the region surrounding the injury, i.e., secondary hyperalgesia, is less well understood, and probably results from changes both in the peripheral and central nervous systems. While considerable advances have been made in our understanding of the mechanisms of acute pain, the pathophysiology of most chronic pain states is still unclear. We hope that future studies in experimental animals, and careful psychophysical testing and microneurographic recordings in chronic pain patients, will lead to a better understanding of the pathophysiology of pain.

Efferent discharges recorded from single skeletomotor and fusimotor fibres in man.

Experiments were performed on awake human subjects in which single nerve fibre activity was recorded in the lateral peroneal nerve using tungsten micro-electrodes as described by Hagbarth & Vallbo (1967, 1968a). The discharge of twelve single efferent fibres innervating the tibialis anterior muscle (t.a.) or the extensor digitorum longus muscle (e.d.l.) was recorded. On the basis of their functional activity, six fibres were identified as skeletomotor and six as fusimotor fibres. Skeletomotor fibres, which were completely silent in relaxed subjects, discharged when subjects performed voluntary isometric or isotonic contractions, they also fired during Jendrassik's manoeuvre and tonic vibration reflex (t.v.r.) induced by mechanical vibration applied to the distal muscle tendon. Units considered as fusimotor fibres were generally spontaneously active with some fluctuation in the discharge frequency. Various tests used to identify afferent fibres elicited no response of these fibres (nor of the skeletomotor fibres). Efferent fibres were considered as fusimotor because their discharges were uncorrelated with any activation of extrafusal muscle fibres. Several means were used to detect activation of extrafusal fibres: surface electromyogram (e.m.g.) electrodes, tungsten electrodes deeply implanted in the muscle and especially the use of a high-sensitivity tension transducer (0 X 1 mN) placed on muscle tendons. The activity in fusimotor fibres could be either elicited or modulated under the following conditions: clenching of the fists, pinna twisting, mental computation, voluntary isometric contraction, passive phasic stretch of the muscle, environmental disturbances, subject laughing, the sound of hand clapping, and subject listening to manoeuvre instructions. Moreover, during spontaneous fusimotor fibre activity the subject was able to voluntarily stop the unit discharge. The results are compared to those obtained in animal studies and discussed with reference to the notion of alpha-gamma linkage, static and dynamic gamma-motoneurone activities, and to other available data concerning the effects of various stimulations on muscle spindle afferent activities in man.

Effects of kainic acid on synaptic transmission in skate electroreceptors (ampullae of Lorenzini)

The effects of kainic acid on synaptic transmission in electroreceptors were investigated in the skate using techniques of uninterrupted superfusion of the synaptic area with a solution containing this substance and then recording the spike activity of single nerve fibers of the ampullae of Lorenzini. Kainic acid at threshold concentrations of the order of 10−9 M effectively changed spontaneous and evoked activity of the receptors. Level of background activity served as an indication of the effects taking place. During blockage of synaptic transmission produced by magnesium ions the addition of kainic acid to the magnesium-saturated solution restored both spontaneous and evoked activity. It was deduced that the action of kainic acid on skate electroreceptors is of a primarily presynaptic nature.

Investigation of the mechanism of temperature sensitivity of the electroreceptors of ampullae of lorenzini

In experiments on Black Sea skates (Raja clavata), the potential of the receptor epithelium of the ampullae of Lorenzini and spike activity of single nerve fibers connected to them were investigated during electrical and temperature stimulation. Usually the potential within the canal was between 0 and −2 mV, and the input resistance of the ampulla 250–400 kΩ. Heating of the region of the receptor epithelium was accompanied by a negative wave of potential, an increase in input resistance, and inhibition of spike activity. With worsening of the animal's condition the transepithelial potential became positive (up to +10 mV) but the input resistance of the ampulla during stimulation with a positive current was nonlinear in some cases: a regenerative spike of positive polarity appeared in the channel. During heating, the spike response was sometimes reversed in sign. It is suggested that fluctuations of the transepithelial potential and spike responses to temperature stimulation reflect changes in the potential difference on the basal membrane of the receptor cells, which is described by a relationship of the Nernst's or Goldman's equation type.

The ampullae of Lorenzini in the magnetic field

1. The impulse activity of single nerve fibers supplying the ampullae of Lorenzini in hyoid group of the Black Sea skate, was recorded to study the response of these receptors to various modifications of stimulation with the vertical component of a magnetic field. 2. When the animal was at rest in motionless water an impulse reaction was observed only with changes in magnetic field, a constant field had no effect. The intensity of response was determined by the rate of magnetic field change (dB/dt). 3. The nature of responses to magnetic field changes depended on the orientation of the ampullary canals relative to induced currents in the animal's body and in the surrounding sea water (Figs. 1, 2 and 3). 4. The intensity of response of a single receptor to magnetic field changes decreased with the shortening of the ampullary canal under study (Fig. 4); cutting of the other canals or dissection of the capsule of the ampullary cluster appeared to have no effect. 5. The receptors of the ampullae of Lorenzini were shown to respond to a constant magnetic field when the fish moved in water, or when water was moved with respect to the fish (Figs. 5 and 6). 6. The character of impulse responses to a constant magnetic field depended on the direction of the field and the direction of movement of either the fish or the water. The relationship between the response intensity and magnetic field, or velocity of water flow is roughly linear (Figs. 7 and 8). 7. Symmetrical receptors on the right and left sides of the animal's body responded oppositely to stimulation by either increasing or constant magnetic field (Figs. 1 and 6). 8. Experiments involving compensation for the Earth's magnetic field with Helmholtz coils revealed a statistically significant reaction to the vertical component of the geomagnetic field (0.35 Gs in the region of the Karadag Biological Station, the Crimea). 9. The mechanisms and functional role of the detection of changing and constant magnetic field by the ampullae of Lorenzini are discussed.

Electrophysiological investigation of the properties of the electroreceptors (ampullae of Lorenzini) in Black Sea rays

Responses of electroreceptors (ampullae of Lorenzini) in Black Sea rays to electrical stimuli were recorded in vivo as spike activity of single nerve fibers. Depending on their functional properties the fibers could be divided into silent, those with regular activity (10–15 spikes/sec) and those with grouped activity. Electrical stimuli evoked a tonic response with a varied degree of adaptation in the nerve fibers. The threshold currents were between 10−10 and 10−11 A/mm2. The minimal latent period of the on-responses to pulses of current of maximal intensity was 15–40 msec, whereas that of the off-responses was 15–200 msec. The effect of intensity, duration, and polarity of the stimuli on the responses of the receptors and the adaptation of the electroreceptors during application of a steady current were investigated. The properties of the ampullae of Lorenzini were compared with those of other types of electroreceptors.

Unit activity from peripheral nerve bundles utilizing correlation techniques

Recording the extracellular neuroelectric activity at several sites along a nerve trunk provides information on single unit action potential shape and conduction velocity. Several correlation techniques are examined for separating the multi-unit neuroelectric activity into the activity of single nerve fibres. An instrument is described that simultaneously separates multi-unit recordings, made at two sites along a nerve trunk, into single unit activity.

Periodicities in efferent discharge of splanchnic nerve of the cat.

Periodicities in efferent discharge of splanchnic nerve of the cat.

Somesthesis and the chemical senses.

.. has been and is still [Adrian (1)] dominated by certain concepts which have proved so convenient that they have come to be accepted without serious question by the majority of physiologists and by many psychologists. These concepts are Muller's so-called of specific nervous energies, and von Frey's extrapolation of this law into the theory of punctate representation of primary sensory modalities. In other words, it is commonly accepted that there are mo;phologically specific pai n, warmth, cold, and touch nerve end­ ings, specific nerve fibres, and specific nerve pathways. It is for this reason that so much emphasis has been laid on the analysis of somesthesis and the chemical senses in terms of the activity of single nerve fibres, which has resulted in reviews that consist of collat ions of literature reporting the results of e1ectrophysiolog ical experiments. Recent anatomical and psycho-physio logical work, however, has seri­ ously challenged the validity of Muller's law and von Frey's theory with re­ gard to cutaneous sensibility, and has made it necessary to re-examine all the experimental observations on the sensory nervous system from a wholly different point of view. This revieJ.V will, therefore, take a somewhat unconventional form. In the first place, we shall examine and collate the evidence which seeks to refute the accepted concepts and then, in the light of these new observations, ex­ amine some of the literature in the field of somesthesis which has appeared in the course of the past year. The literature on the chemical senses was ably reviewed in Volume 5 of the Annual Review of Psychology and for this reason has been dealt with less exhaustively on this occasion. The review is intended to be provocative and critical, and necessarily reflects the author's personal opinion of the evidence before him. SOMESTHESIS Recent observations on the mechanism of cutaneous sensibility.- The state­ ments which follow are based on a series of publications by Weddell and his co-workers (2 to 21) , some of which appeared before 1953. Reference should be made to all of these publications if exhau stive examination of the evi­ dence is desired. Neurohistologica l

Rhythmic Activity of Single Nerve Fibers Induced by Low Calcium

In the course of certain experiments on the chemical excitation of nerve we have observed the development of rhythmic volleys of impulses in the individual fibers which recur at regular intervals for long periods of time. Because of the possible relation of such a phenomenon to the mechanism of rhythmic activity of the nervous system in normal and pathological states we have studied this type of response in some detail. All of the experiments have been performed on the sciatic nerve of the frog. In order to facilitate the penetration of the solution used for stimulation the sheath of the excised nerve was removed for a length of about one cm. and here the fibers were carefully separated so as to form a large number of small bundles. The region thus treated with the solution was usually at one end, but it was equally satisfactory to do so anywhere along the course of the nerve. A single fiber was then isolated at the other end of the nerve and placed on non-polarizable electrodes leading to an amplifier and oscillograph. Partial removal of the ionized calcium in the nerve by sodium citrate or a reduction of its concentration by bathing the fiber bundles in calcium-free Ringer's fluid initiates a continuous train of impulses from the treated end at the rate of about 1001 per sec. When the nerve fiber has been brought into this condition which causes a sustained discharge of impulses we find that the substitution of normal Ringer's fluid for the citrate or the calcium-free solution ultimately transforms the discharge into a series of rhythmic volleys. The continuous discharge goes on for a time which is variable from preparation to preparation and then suddenly stops, followed after an interval of a few seconds by a burst of impulses.