Central vagal organization in rats: An electrophysiological study

The organization of the vagal nuclei was studied electrophysiologically in chloralose-anesthetized rats by analyzing the field potentials and unitary responses evoked in the nuclei by stimulation of the cervical vagus nerve. The rostral part of the nucleus commissuralis yielded only a long-latency response to stimulation of this nerve, suggesting that this region receives projections solely of nonmyelinated afferent fibers. In the nucleus tractus solitarius the stimulation elicited both short-latency and long-latency responses, indicating converging projections of myelinated and nonmyelinated afferents. A long-latency response was recorded diffusely within n. commissuralis and n. tractus solitarius of the contralateral side, whereas a short-latency response was restricted to a midline area, the caudal n. commissuralis, and the most medial part of n. tractus solitarius adjacent to it. These observations also suggest a difference in projections of myelinated and nonmyelinated afferents. Two types of motor neurons were identified in the dorsal vagal nucleus by antidromic activation: one with B-fiber axons and the other with C-fiber axons. C-Fiber motor neurons were characterized by the large positivity of the spike and the presence of an inflection in the rising phase of the spike, presumably between the initial segment and somatodendritic components. The latter component was readily blocked by repetitive stimulation. In the nucleus ambiguus, stimulation of the vagus nerve produced the earliest antidromic response of A-fiber motor neurons accompanied by multiple orthodromic responses of short and long latencies. Electrolytic lesions of the dorsomedial medulla oblongata abolished all potentials in n. ambiguus except the antidromic one, indicating that all the orthodromic responses were generated via the vagal sensory nuclei sinuated dorsomedially.     

Sympathetic preganglionic neurons in the isolated spinal cord of the neonatal rat

A preparation of the isolated spinal cord of the neonatal rat was developed for the study of sympathetic preganglionic neurons (PGNs). PGNs were identified for extracellular single unit recording by their location and by antidromic activation by ventral root stimulation. PGNs could be synaptically activated by stimulation of the dorsal root and spinal pathways. Spontaneous firing was observed in 18% of the PGNs. The average firing rate was 1 Hz with a range of 0.3 to 2 Hz.PGNs (and motoneurons) were visualized by incubating vental roots in horseradish peroxidase (HRP) solutions. The location and morphology of PGNs were similar to those reported in studies using adult animals. Primary afferent fibers were visualized by incubating dorsal roots in HRP solutions. Dorsal root projections appeared mature in the neonatal rat. Primary afferents did not appear to project directly to PGNs.It is concluded that PGNs are viable in this preparation and that spinal sympathetic systems are relatively mature in the neonatal rat.     

Development and maturation of postural reflexes in normal kittens

Electrical stimulation of the hypothalamus in rats anesthetized with chloralose-urethane evoked antidromic responses in 5% of the neurons in the nucleus tractus solitarius (NTS) which responded orthodromically to vagus nerve stimulation. The NTS neurons with such a direct forebrain projection (F-NTS neurons) were distributed mostly in the lateral part of the ipsilateral commissural NTS. Latencies of the antidromic responses ranged from 20 to 75 ms, indicating that the axons of the F-NTS neurons were unmyelinated. Orthodromic responses (latencies, 20 to 80 ms) were observed in 6 of 23 F-NTS neurons, to the same stimuli that evoked the antidromic responses. Sites that elicited antidromic responses in the F-NTS neurons upon stimulation covered almost all medial hypothalamic nuclei, but 65% were localized in the preoptic-anterior hypothalamic region. All orthodromic responses to activation of vagal afferent fibers (either myelinated or unmyelinated) were polysynaptic in nature. Three F-NTS neurons were found to project to two different hypothalamic regions, by axonal branching. In addition, the firing rate of most F-NTS neurons was not appreciably affected by norepinephrine-induced blood pressure increase. It is concluded that vagal visceral input is transmitted polysynaptically to the F-NTS neurons and is then conveyed to the forebrain via the direct pathway.     

Solitary nucleus neurons transmitting vagal visceral input to the forebrain via a direct pathway in rats

Electrical stimulation of the hypothalamus in rats anesthetized with chloraloseurethane evoked antidromic responses in 5% of the neurons in the nucleus tractus solitarius (NTS) which responded orthodromically to vagus nerve stimulation. The NTS neurons with such a direct forebrain projection (F-NTS neurons) were distributed mostly in the lateral part of the ipsilateral commissural NTS. Latencies of the antidromic responses ranged from 20 to 75 ms, indicating that the axons of the F-NTS neurons were unmyelinated. Orthodromic responses (latencies, 20 to 80 ms) were observed in 6 of 23 F-NTS neurons, to the same stimuli that evoked the antidromic responses. Sites that elicited antidromic responses in the F-NTS neurons upon stimulation covered almost all medial hypothalamic nuclei, but 65% were localized in the preoptic-anterior hypothalamic region. All orthodromic responses to activation of vagal afferent fibers (either myelinated or unmyelinated) were polysynaptic in nature. Three F-NTS neurons were found to project to two different hypothalamic regions, by axonal branching. In addition, the firing rate of most F-NTS neurons was not appreciably affected by norepinephrine-induced blood pressure increase. It is concluded that vagal visceral input is transmitted polysynaptically to the F-NTS neurons and is then conveyed to the forebrain via the direct pathway.     

Observations on the sensory nature of the intramuscular nerve action potential

The nature and the origin of the small pre-potential wave which can be recorded immediately before the main muscle action potential on indirect stimulation was studied in the median nerve of 12 normal subjects. It is considered to be a sensory antidromic response recorded from the large afferent fibres which innervate the thumb because it was recorded in all 12 subjects, and the threshold was always below the motor threshold. An antidromic response was recorded with stimulating electrodes at the thumb and recording electrodes at the palm. Both antidromic and orthodromic responses were recorded with stimulating electrodes at the palm. The amplitude of the pre-potential was higher at the recording point closest to the sensory fibres for the thumb and progressively decreased with distance in the other points.     

Association of neurotensin binding sites with sensory and visceromotor components of the vagus nerve

Specific neurotensin (NT) binding sites were recently shown to be highly concentrated in the nucleus of the solitary tract (NTS), which receives primary vagal afferents, and in the dorsal motor nucleus of the vagus (DMN), which contains the cell bodies of origin of vagal preganglionic neurons. To investigate the relationship of these binding sites with sensory and visceromotor components of the vagus nerve, they were labeled here in vitro, using monoiodo[Tyr3]neurotensin (125I-NT) and visualized by light microscopic radioautography in the dorsomedial medulla of both intact and unilaterally vagotomized rats, in the nodose ganglia of intact animals, and in ligated vagus nerves. Unilateral vagotomy performed above the nodose ganglion resulted in a significant ipsilateral decrease in 125I-NT binding within both the NTS and the DMN, suggesting that NT binding sites were associated with both primary afferent fibers and preganglionic nerve cell bodies. The selective radioautographic labeling of a subpopulation (approximately 15%) of neuronal perikarya in the nodose ganglion confirmed that a proportion of vagal afferent neurons contained NT binding sites. Following vagus nerve ligation, a pile up of radiolabeled NT binding sites was observed on both sides of the nerve crush, indicating that NT receptor components were transported both anterogradely and retrogradely along fibers of the vagus nerve. We conclude that NT receptors are synthesized and transported within a subpopulation of afferent and efferent components of the vagus nerve and that NT may therefore act presynaptically upon vagal axon terminals in both central and peripheral nervous systems.     

Investigation of the vagally induced changes in transmural potential difference in the ferret jejunum in vivo

This study was designed to determine whether the non-cholinergic, non-adrenergic rise in transmural potential difference (PD), induced by vagal nerve stimulation is an efferent effect or one caused by the antidromic stimulation of afferent fibers. Unilateral left supranodose vagotomy was performed, which caused degeneration of efferent fibers within the vagus nerve, leaving the nodose ganglion, and consequently afferent cell bodies, undamaged. After stimulating the unoperated nerve there was an increase in jejunal motility, a rise in transmural PD and a fall in systemic blood pressure. Although cholinergic blockade with atropine and adrenergic blockade with or a combination of phentolamine and propranolol abolished this vagally induced motor activity and fall in systemic blood pressure, the transmural PD response induced by stimulation of the unoperated nerve was only partially inhibited. However, the subsequent administration of the nicotinic ganglionic blocker, hexamethonium, abolished this transmural PD response. In contrast, stimulation of the operated vagus nerve failed to produce these effects. Therefore, cholinergic and non-cholinergic efferent fibers are responsible for the vagally induced rise in transmural PD and thus fluid secretion in the ferret jejunum.     

Antidromic activation of vagal and sympathetic afferents does not produce intestinal contractions in dogs.

The question has been asked whether vagal and sympathetic afferents activated antidromically play a role as motor nerves on the in vivo small intestine in dogs anesthetized with urethane. The vagus nerve of one side was cut above the nodose ganglion and the efferent fibers allowed to degenerate. Peripheral stimulation (5-50 Hz, 0.5-3 ms, 5-25 V) of an intact cervical vagus, being able to excite both efferent and afferent fibers, caused large contractions in the jejunum and stomach, whereas stimulation of the contralateral cut cervical vagus could not produce any response in the jejunum but small contractions in the stomach. Peripheral stimulation of the cut cervical vagus did not produce bradycardia and hypotension. Single- and multi-unit discharges to distension of the jejunal segments could be recorded from the peripheral cut end of the cut cervical vagus. Immunohistochemically, there were many substance P-containing cells in both nodose ganglia. Antidromic stimulation of the dorsal roots (T7-T10) did not induce any response in the jejunum but contractions in the stomach. The results may confirm that vagal and sympathetic afferents have no antidromic motor function at least in the in vivo canine small intestine.     

Abnormal muscle responses in hemifacial spasm: F waves or trigeminal reflexes?

OBJECTIVE: In patients with hemifacial spasm (HFS), abnormal muscle responses (AMR) are frequently present. The objective of this study was to investigate whether the afferent input of AMR is mediated by antidromic facial nerve stimulation or orthodromic trigeminal nerve stimulation. METHODS: AMR in the orbicularis oris muscle were recorded in 28 patients with HFS. When AMR were present, they were recorded after subthreshold stimulation of the facial nerve and weak stimulation delivered to the skin. RESULTS: AMR were recordable in 24 (86%) of the patients, and usually consisted of the early constant component (mean onset latency, 10.0 ms) and late variable component (35.3 ms), similar to R1 and R2 of the blink reflex. The early or late components of AMR, or both, were frequently elicited after subthreshold stimulation of the facial nerve (43%) and skin stimulation (88%). CONCLUSIONS: AMR are likely to be mediated by trigeminal afferent inputs, rather than antidromic activation of the facial nerve, and are a type of trigeminal reflex.     

A quantitative model of the Hoffmann reflex

Electrical stimulation of the human posterior tibial nerve elicits two separate electromyographic responses. The shorter latency response results from electrical activation of motor axons and is termed the direct motor (M) response, while the longer latency response results from activation of stretch receptor afferents of the monosynaptic reflex arc and is termed the Hoffmann (H) reflex. At high stimulus intensities, the H reflex is either greatly reduced in size or completely extinguished, presumably by antidromic impulses elicited by stimulation of the motor nerve. In most subjects, a simple quantitative model appears to account for this extinction. In this model: (1) the M response is used to estimate the number of antidromic impulses; (2) the H reflex is used to estimate the number of orthodromic impulses which escape collision; (3) the maximum size of the M response is used to indicate the size of the motoneuron pool; and (4) it is assumed that antidromic impulses collide in a random fashion with orthodromic impulses in the motor nerve.     

A Quantitative Model of the Hoffmann Reflex

Abstract

Electrical stimulation of the human posterior tibial nerve elicits two separate electromyographic responses. The shorter latency response results from electrical activation of motor axons and is termed the direct motor (M) response, while the longer latency response results from activation of stretch receptor afferents of the monosynaptic reflex arc and is termed the Hoffmann (H) reflex. At high stimulus intensities, the H reflex is either greatly reduced in size or completely extinguished, presumably by antidromic impulses elicited by stimulation of the motor nerve. In most subjects, a simple quantitative model appears to account for this extinction. In this model: (1) the M response is used to estimate the number of antidromic impulses; (2) the H reflex is used to estimate the number of orthodromic impulses which escape collision; (3) the maximum size of the M response is used to indicate the size of the motoneuron pool; and (4) it is assumed ,that antidromic impulses collide in a random fashion with orthodromic impulses in the motor nerve.     

Responses of inferior salivatory neurons to stimulation of trigeminal sensory branches

A total of 84 single inferior salivatory neurons was identified by antidromic stimulation of the tympanic nerve. Their responsiveness was tested to stimulation of the ipsilateral infraorbital, lingual, and inferior alveolar nerves in urethane-chloralose-anesthetized cats. The conduction velocities of preganglionic fibers of inferior salivatory neurons ranged from 2.2 to 9.1 m/s, and 54% of those neurons responded with spikes to stimulation of at least one of the infraorbital, lingual, or inferior alveolar nerves (responsive type neurons). The latencies of spike responses to stimulation of the trigeminal sensory branches ranged from 4.0 to 21.0 ms, which were shorter than those of superior salivatory neurons. Impulses of both A-beta and A-delta afferent fibers of the trigeminal nerve were found to be effective for activation of inferior salivatory neurons. The convergence of excitatory inputs from more than one sensory nerve was found in most of the responsive type neurons (73%).     

Does stimulation of sympathetic axons elicit an increase in cat spindle afferent discharge detectable by the antidromic collision technique?

Averaged antidromic action potentials of Group I and Group II fibres elicited in cats by stimulation of L7 and S1 dorsal roots were recorded from intact tibial nerves (near the ankle) either in absence of or during repetitive stimulation of the ipsilateral lumbar sympathetic chain. This was done to test the suggestion that stimulation of noradrenergic sympathetic axons may elicit, in spindles of foot muscles, a substantial increase in the firing rate of secondary endings, capable of reducing the size of afferent antidromic volleys by collision with orthodromic impulses. We found that potentials recorded during sympathetic stimulation were identical to those recorded in absence of stimulation. The reduction in size of a component of the compound action potentials led from the intact tibial nerve during stimulation at 10-20 Hz of the sciatic nerve with C strength pulses, as described by Grassi, Filippi and Passatore (Brain Research, 435 (1987) 15-23), was observed in certain conditions of stimulation. However this reduction cannot be ascribed to antidromic collision, because it is still observed after severing the tibial nerve distal to the recording electrode.     

Recurrent potentials in human peripheral sensory nerve: possible evidence of primary afferent depolarization of the spinal cord.

To study slowly conducted components of the orthodromic compound sensory action potential (CSAP), the response evoked at the lateral malleolus in the sural nerve was recorded through near-nerve needles at two to four sites along the nerve at midcalf. When 500 to 2000 responses were averaged at high gain, components with latencies of 30 to 80 ms were often recorded. In contrast to the main component and late components with latencies of less than 15 to 20 ms, the latencies of these extremely late components diminished the closer to the spinal cord that they were recorded. This suggested that the components were conducted antidromically from proximal to distal. This assumption was supported by abolishing the components by local anesthesia of the nerve proximal to the recording electrodes. These antidromic potentials therefore appear to be due to recurrent discharges in the sural nerve. Recurrent discharges were recorded from 65% of 60 subjects (18 normal subjects and 42 patients with peripheral or central nervous system disorders). The latencies of the recurrent discharges allowed conduction to and back from the spinal cord. Although the origin of these potentials remains unknown, we suggest that they are due to dorsal root reflexes within the spinal cord. In this case, the responses may be a direct expression of primary afferent depolarization (PAD) seen in presynaptic inhibition, and may be of value in further studies on the physiology and pathophysiology of presynaptic inhibition of cutaneous fibers in man.     

Inhibition of motoneuron discharge by peripheral nerve stimulation: an F response analysis

F waves were recorded from the abductor pollicis brevis stimulating the median nerve at the wrist. These data were compared to responses obtained after preceding supramaximal stimulation of digital fibers of the second (II) finger or the median nerve at the wrist. The time between conditioning and test stimuli were 50 msec. Following conditioning stimuli, F wave latencies were significantly increased while F amplitudes, durations, and persistences were all decreased. Chronodispersion was not significantly affected. These changes were associated with increased repetition of individual F responses. The most prominent changes were found after stimulation of fibers of digit II but only at levels of stimulation supramaximal for the sensory nerve action potential. Some, but relatively limited, changes were present after stimulation of digital fibers of the fifth finger. The results are consistent with afferent fiber, probably A delta, inhibition of antidromic motoneuron activation with associated decrease in central motor neuron pool excitability. The study also demonstrates that, except for chronodispersion, changes in F waves found with peripheral nerve injury may also occur due to physiological changes in the central nervous system.     

Orthodromic and antidromic activation of the paraventricular nucleus of the hypothalamus in the rabbit

Paraventricular cells in the rabbit were studied in response to stimulation in the hypothalamohypophyseal tract and the afferent pathway from the mammary gland. Three conditions were used in different preparations: urethane-anesthesia, unanesthetized and unanesthetized following the administration of monoamine depletors. Hypothalamohypophyseal stimulation antidromically activated paraventricular cells similarly in all three preparations. Long-lasting inhibition was also seen in all three. Transsynaptic activation was most common in the two unanesthetized preparations and rare in anesthetized rabbits. Orthodromic activation from stimulation in the afferent pathway activated the paraventricular cells and elicited milk ejection only in the preparation in which monoamine depletors were used. In these experiments it was possible to demonstrate collision between antidromic and orthodromic impulses in paraventricular cells. The results suggest that there is central monoamine inhibition which prevents activation of the nucleus under certain experimental situations.     

A new aspect of the collision test principle: cell body distance from recording site

A theoretical method is described for estimating the distance between a spike recording-site, possibly axonal, and the corresponding cell body of unknown location. The method requires that an orthodromic spike be recorded following an antidromic spike, with estimation of a collision interval analogous to that used for establishing antidromicity. To calculate the distance between recording-site and cell body, values are needed for the collision interval between antidromic and succeeding orthodromic spikes, the refractory period of the spike, and the antidromic conduction speed. Problems may arise in determining the last value. The method is illustrated with antidromic spikes recorded in the medial thalamus of the cat upon stimulating the caudate nucleus.     

Projection of the hepatic vagal nerve in the medulla oblongata

Afferent neurons in the solitary tract nucleus (NTS) which innervate the liver were identified by electrical stimulation of the hepatic branch of the vagus. This nerve branch projects predominantly into the left side of the medulla. A collision test was employed to discriminate the afferent unit discharges from the efferent ones. These afferent neurons are characterized by no cancellation of the evoked unit discharges by the collision. Latencies were widely scattered and lay between 73.2 and 222.5 ms. A variable latency in each response was always recognized. Excitability curves obtained by applications of conditioning and test stimuli revealed that there exist two different types of units; one is characterized by a higher safety factor for synaptic transmission, while the other shows a lower safety factor than the former. It is concluded that the neurons in the NTS activated by the hepatic vagal afferent nerve locate predominantly in the left side of the medulla and also these nerve fibers are mostly non-medullated fibers in which conduction velocities are slower than 1 m/s. The variable latency recognized in each neuron and low safety factors for synaptic transmission recognized in some neurons indicate integrative action within the NTS as well as a relay of the afferent signals from the liver.     

Optic nystagmus and vestibular nuclei: Unitary activity of vestibular neurons during nystagmus

The behavior of 102 vestibular neurons during optic nystagmus was investigated in 25 guinea pigs with extracellular microelectrodes. The recorded vestibular neurons were electrophysiologically identified by their orthodromic response to ipsilateral labyrinthine stimulation and by antidromic activation from the medial longitudinal fascicle. Of the 102 recorded units, 92 were modulated by the electrical stimulation of at least one optic nerve. The presence of vestibular neurons sensitive to the direction of nystagmus induced by labyrinthine or optic stimulation was also analyzed.     

The effect of supranodose vagotomy on the hexamethonium-resistant bradycardia in the anaesthetized rabbit

Previous studies from this laboratory have established that electrical stimulation of non-myelinated axons in the rabbit vagus nerve produces a bradycardia which is unaffected by the nicotinic ganglion blocker hexamethonium. The present study was undertaken to determine whether this effect is mediated by afferent or efferent axons. A unilateral supranodose vagotomy was performed on four New Zealand White rabbits, one further animal served as a sham-operated control. Fourteen days later the effects of vagal nerve stimulation (10 Hz, 20 s) were assessed. On the operated side, where the supranodose vagotomy would have led to the degeneration of efferent axons, vagal stimulation had no effect on heart rate. The integrity of afferent axons was demonstrated by recording both electrically evoked volleys and characteristically normal patterns of afferent activity from the nerve. On the unoperated side the bradycardia produced by vagal stimulation was consistent with previous studies. It is concluded that the hexamethonium-resistant bradycardia evoked by stimulation of the rabbit vagus is mediated by non-myelinated preganglionic efferent axons.