Afferent Units Research Articles

The effect of topical turpentine on the functional properties of cutaneous afferents in the anaesthetized rat

Turpentine was applied to the rat dorsal hindpaw over 1.5–3.5 h and afferent activity was recorded for 1.5–7 h after its removal. Increased spontaneous activity from both A- and C-fibres was observed. There was an increase in units with no response to natural stimuli and a reduction in the numbers of all types of afferent unit, with some recovery of the C- and A δ-classes during the recording period. Surviving C-polymodal nociceptor units had normal sensitivity to noxious heat, but higher mechanical thresholds. Thus turpentine application caused no nociceptor sensitization. Instead, the many insensitive units plus the generalized spontaneous firing may be signs of non-specific axonal damage. A general division of irritant chemicals into those that are predominately damaging, like turpentine, and those that generate specific nociceptor firing or sensitization, is proposed.

Mechanosensitive afferent units in the lateral ligament of the ankle.

We have studied the mechanosensitive afferent units in the lateral ligament of the ankle of the cat, with reference to the causes of lateral instability after injury, using electrophysiological recording from the lumbar dorsal rootlets. We identified 30 mechanosensitive units in the lateral ligament; 28 (93%) were located near the attachment to the fibula and calcaneus, which included both low-threshold group-II units and low- and high-threshold group-III units. Our results indicate that there are both proprioceptors and nociceptors in the lateral ligament of the cat ankle, and confirm that afferent fibres from the lateral ligament may contribute to the stability of the joint by regulation of position and movement.

MECHANOSENSITIVE AFFERENT UNITS IN THE LATERAL LIGAMENT OF THE ANKLE

We have studied the mechanosensitive afferent units in the lateral ligament of the ankle of the cat, with reference to the causes of lateral instability after injury, using electrophysiological recording from the lumbar dorsal rootlets. We identified 30 mechanosensitive units in the lateral ligament; 28 (93%) were located near the attachment to the fibula and calcaneus, which included both low-threshold group-II units and low- and high-threshold group-III units. Our results indicate that there are both proprioceptors and nociceptors in the lateral ligament of the cat ankle, and confirm that afferent fibres from the lateral ligament may contribute to the stability of the joint by regulation of position and movement.

Capsaicin and carbon dioxide act by distinct mechanisms on sensory nerve terminals in the cat cornea

The discharge of single afferent units recorded from filaments of the mixed ciliary nerve of anaesthetised cats was used to study the effects of CO 2, capsaicin and the capsaicin antagonist, capsazepine, on sensory nerve terminals in the cornea. Units were selected on the basis of their sensitivity to CO 2 (98.5% applied to the cornea for 30 s in a moist gas stream). Of these units, about 50% (18/38) also responded to capsaicin (0.1 μM applied as droplet and washed off after 20 s), with a discharge of similar magnitude to that produced by CO 2. The other CO 2-sensitive units (20/38) did not respond to capsaicin. Capsaicin-sensitive units responded more rapidly to CO 2 (mean latency to first spike 0.7±0.2 s) than capsaicin-insensitive units (mean latency to first spike 5.1±1.2 s). On the basis of their conduction velocity, both the capsaicin-sensitive and the capsaicin-insensitive groups included both A- and C-fibres. Application of capsazepine (10 μM for 5–20 min) to the cornea reversibly blocked the response of the units to capsaicin without affecting responses to CO 2. Units that were acutely desensitised by exposure to capsaicin (0.1 μM) for 30 s, during which time the discharge evoked by capsaicin declined to zero, still responded to CO 2, though the response was reduced by 44% compared with controls. It is concluded that activation of sensory afferents in the cat cornea by capsaicin and by CO 2 appear to involve distinct mechanisms, since: (a) many CO 2-sensitive units are not excited by capsaicin; (b) capsazepine selectively blocks excitation by capsaicin without affecting responses to CO 2; and (c) desensitisation to capsaicin impairs only partially the responsiveness to CO 2.

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.

Primary afferent neurons innervating guinea pig dura.

We made recordings from filaments of guinea pig nasociliary nerve to study response properties of afferent axons innervating the anterior superior sagittal sinus and surrounding dura mater. We analyzed 38 units in 14 experiments. Units were initially located with the use of mechanical stimuli, and were then characterized by their conduction velocity and sensitivities to mechanical, thermal, and chemical stimuli. Single-unit recordings revealed innervation of dura and superior sagittal sinus by slowly conducting axons, mostly in the unmyelinated range. The receptive fields were 1-30 mm2, and typically had one to three punctate spots of highest sensitivity. All units tested responded to topical application of chemical agents. Ninety-seven percent of units responded to 10(-5) M capsaicin, 79% responded to a mixture of inflammatory mediators, and 37% responded to an acidic buffer (pH 5). These data underline the importance of chemical sensitivity in intracranial sensation. Heat and cold stimuli evoked responses in 56 and 41% of units tested, respectively. Although the response patterns during heating were typical of polymodal nociceptors innervating other tissues, the thresholds were lower than for other tissues (32.3-42 degrees C). Cooling led to a phasic discharge, with thresholds between 25 and 32 degrees C. Although units had different combinations of responses to mechanical, chemical, and thermal stimuli, when grouped by their sensitivities the groups did not differ regarding mechanical thresholds or presence of ongoing activity. This suggests that meningeal primary afferents are relatively homogeneous. Sensitivities of these units are in general consistent with nociceptors, although the thermal thresholds differ. These data provide the first detailed report of response properties of intracranial primary afferent units, likely to be involved in transmission of nociception and possibly mediation of intracranial pain.

Stimulation of group III and IV afferent nerves from the hindlimb by thromboxane A 2

These experiments were designed to test the hypothesis that the TxA 2 mimetic, U46,619, would stimulate group III and IV afferent nerve endings from the hindlimb of the anesthetized cat. Nerve impulses were recorded from the dorsal rootlets of the L7-S1 segments of the spinal cord, and afferent units identified by measurement of conduction velocities, mechanical probing of hindlimb muscles, and local injection of chemical stimulants (capsaicin and bradykinin). Five of the 15 group III fibers were stimulated by U46,619 (2–10 μg injected into the abdominal aorta; mean baseline impulse frequency increasing from 7.3 (±3.2) impulses/s to 16.0 (±3.1)), while 7 of the 12 group IV fibers responded to U46,619 (impulse frequency increasing from 4.3 (±3.2) to 8.8 (±3.6)). The average latency for the response (20–30 s) did not differ between the two groups of afferent fibers. We conclude that group III and IV afferent fibers originating from the skeletal muscle of the hindlimb are stimulated by TxA 2 and that the release of TxA 2 in skeletal muscle could evoke cardiorespiratory reflexes known to be activated by stimulation of these afferent nerves.

The Merkel cell as a possible mechanoreceptor cell

Merkel cells (MCs) are abundant at the basal layer of various skin in vertebrates, and make synaptic contacts with nerve endings to form the Merkel cell-neurite complex (MCN-complex). It has been established that the MCN-complex is involved in slowly adapting mechanoreception, cutaneous afferents of which are called SAI units in mammals or Ft-I units in frogs. However, the MC function has been the focus of attention, and some hypotheses propose that the site of mechanoreception is at the nerve terminals but not at the MC. In the present review, the possibility that MCs are the mechanoreceptors was focused on recent findings. Irradiation of quinacrine-loaded MCs in the rat hairy skin using excitation light degenerates the MCs selectively with the nerve terminals left intact. Correspondingly, SAI units decrease tonic discharges rapidly, but phasic responses remain intact. Blocking synaptic transmission in the MCN-complexes by divalent or alkyl Ca antagonists in mammals or frogs heavily decreases the tonic mechanical responses of the afferent units, but the phasic responses are rather resistant. Application of anodal current on the Ft-I receptive spots produces tonic discharges as in hair cells or taste cells, while the threshold to elicit the first spike is lower with cathodal than anodal stimulation, in contrast with other secondary sensory cells. These findings indicate that MCs are mechanoreceptors to yield tonic responses, while the nerve terminals may transduce the transient phase. Further studies, particularly on mechanically-gated ionic channels in the MC membrane and on transmitters between the MCs and nerve terminal, are necessary to establish the MC as mechanoreceptors.

New Developments in Microneurography of Human C Fibers

Slowing of conduction velocity during the relative refractory period of an axon can be used to detect activation in human cutaneous nerve fibers. The method is highly sensitive and provides the means to identify individual unmyelinated afferent and efferent (sympathetic) units excited by different types of stimuli.

Alteration of human cutaneous afferent discharges as the result of long-lasting vibration

The unitary activities of slowly (15 SAI) and fast-adapting type I (12 FAI) skin mechanoreceptive afferent units innervating the anterior part of the human leg and foot were recorded by using the microneurographic method. The recordings were performed both at rest and on application of cutaneous stimuli of various intensities before and after exposure of the corresponding receptive fields to vibration (0.5 mm peak to peak, 100 pulses/s, 10 min). The results show that 11% of the units tested, which were previously silent, developed a bursting pattern of postvibratory activity, which lasted 12 min on average. This induced resting activity may account for the tingling sensations usually perceived after exposure to vibration. Furthermore, application of vibration to the cutaneous receptive fields impaired the response properties of the corresponding cutaneous fibers much more markedly in the case of the SAI than in the FAI units. More specifically, less than one-half of the FAI fibers tested showed a postvibratory depressed sensitivity to skin stroking applied at various velocities that persisted for only a few minutes, whereas the responses of all the SAI units to suprathreshold maintained skin indentations applied with increasing amplitudes decreased significantly for 20 min. These fairly durable changes in the transductive properties of the mechanoreceptive afferent units probably lead to an impairment of perceptual and sensorimotor processes and consequently may at least partly account for the alterations in sensorimotor performance that have been reported to occur in humans after exposure to vibration.

Response patterns and postspike effects of premotor neurons in cervical spinal cord of behaving monkeys

Most of our information about spinal neurons has been derived from experiments with anesthetized or surgically. reduced preparations. To investigate these neurons under normal behavioral conditions, we recorded the activity of single afferent units in cervical dorsal root ganglia and of single interneurons in the cervical spinal cord of macaque monkeys, as they generated alternating flexion and extension torques about the wrist. Spike-triggered averages of rectified electromyographic activity were used to identify "premotor" (PreM) units associated with correlated postspike effects in active muscles. In addition to postspike effects, some spike-triggered averages showed early increases in average muscle activity, which were attributed to synchronous discharges in other PreM units. In recordings of peripheral afferents, 49% of the task-related dorsal root ganglia units produced postspike facilitation (PSF) of at least one forearm muscle, with a mean PSF latency of 5.8 +/- 0.3 ms (SE). The PSF amplitude was measured as the mean percent increase (MPI): the average increase of the PSF as a percentage of the prespike baseline mean. PreM afferent units produced PSF with an average MPI of 4.6 +/- 0.3%. In a study of cervical interneurons, about 13% (72/562) of the task-related cells showed postspike effects. These PreM interneurons had a mean PSF latency of 7.2 +/- 0.3 ms and a mean MPI of 4.6 +/- 0.2%. The MPI values for spinal neurons were similar to the MPIs reported for rubromotoneuronal and corticomotoneuronal cells. PreM neurons usually facilitated a subset of the coactivated muscles called the unit's "muscle field." The PreM afferents facilitated an average of 46% of the synergistically coactivated muscles, while PreM interneurons facilitated an average of 37%. These are comparable with the percentage of muscles facilitated by corticomotoneuronal (40%) and rubromotoneuronal (50%) cells. During the step-tracking task the monkeys generated ramp-and-hold torques about the wrist. The PreM afferents typically became active during either flexion or extension of the wrist, although a few were bidirectionally active. The most common response pattern in PreM afferents was a tonic discharge, followed by phasic and phasic-tonic discharge. The most common patterns exhibited by PreM interneurons were tonic and phasic-tonic responses. PreM afferent units began to discharge on average 51 +/- 13 ms before activation of their target muscle. This early onset supports our hypothesis that these PreM afferents arose from muscle spindles, which is also consistent with their short-latency PSF and their responses to perturbations that stretched their target muscles. The results reveal some salient differences between the discharge properties of dorsal root ganglia neurons, spinal interneurons, and supraspinal PreM cells in the motor cortex and red nucleus. All four PreM populations include tonic, phasic-tonic, and phasic cells, but in significantly different proportions. Most PreM afferents resembled corticomotoneuronal cells in being active only with their target muscles, unlike rubromotoneuronal cells and spinal PreM interneurons, which tended to exhibit more bidirectional discharges.

Chapter 4. The articular polymodal nociceptor in health and disease

Publisher Summary This chapter focuses on the properties of peripheral polymodal nociceptors taking articular polymodal nociceptors as an example and discusses the properties of those afferent units that, in health and disease, transmit noxious information from the joints to the central nervous system. A further structural aspect of fine afferents in joint nerves with considerable functional implications is that many of these afferents contain neuropeptides. In order to identify the proportion of joint afferents containing particular neuropeptides, the dorsal root ganglion cells of knee joint afferents have been labeled with Fast Blue (this marker is retrogradely transported) and treated with antisera to several neuropeptides. Findings show that an involvement of thick myelinated afferents in the signaling of noxious events in the joint seems to be possible. Therefore, their response properties under normal and inflamed conditions has to be mentioned, albeit briefly.

A new combination of methods for the localization, identification, and three-dimensional reconstruction of the sensory endings of articular afferents characterized by electrophysiology.

A combination of methods is described to identify and reconstruct corpuscular and non-corpuscular sensory endings of group II and group III nerve fibers following functional examination by electrophysiology. Afferent units activated by electrical stimulation of the medial articular nerve of the cat's knee were analyzed by single fiber recordings and characterized by their responsiveness to mechanical stimuli. The receptive fields of the units were closely demarcated by fine needles when the responses elicited by insertion of the needles were being recorded. After fixation, the tissue around the demarcated field was dissected and histologically processed. Series of semithin sections were cut from the embedded tissue blocks containing the receptive fields. Corpuscular endings of group II fibers and peripheral myelinated group III nerve fibers, presumably corresponding to the characterized units, were identified by light microscopy of semithin sections and localized within the demarcated area. Non-corpuscular endings were identified by electron microscopy of ultrathin sections cut in alternation with, or after re-embedding of, semithin sections. Morphometric analysis of ultrathin section series allowed the measurement of parameters such as the mean axon diameter and the organelle content of the sensory endings. The methods described are appropriate for collecting data that correlate the structural and functional characteristics of sensory endings in deep tissues.

Unmyelinated nociceptors of rat paraspinal tissues

1. We made recordings from rat dorsal root filaments to study unmyelinated afferent units (conduction velocity < or = 1.5 m/s) associated with deep paraspinal tissues of the dorsal sacrum and proximal tail. Data from 57 unmyelinated units were analyzed in 47 experiments. Receptive fields were identified in intact animals and then surgically isolated using microdissection. Units were characterized using mechanical, noxious chemical, and thermal stimuli. 2. These recordings revealed innervation of the nerve sheaths and surrounding connective tissue, muscles, tendons, and tissue apposed to the undersurface of the skin. No units were found with receptive fields directly on joint capsular tissue. The receptive fields of the units were often multiple and located in more than one tissue; 31 of 57 units showed convergence from different tissues. 3. The units with receptive fields on neurovascular bundles shared sensitivities with other deep tissue units described in this and other reports. These units may have clinical importance in pain due to peripheral neuropathies. 4. The units initially responded to strong mechanical stimulation of the intact animal and often to noxious stretch of the tail. Once surgically isolated, an individual unit's threshold to mechanical stimuli appeared lower. 5. Capsaicin (0.001%-0.1%) elicited responses in 81% (17 of 21) of the units tested. Bradykinin (20 micrograms/ml) elicited responses in 45% (10 of 22) of the units tested. Noxious cold (4-10 degrees C) and hot (55 degrees C) stimulation elicited discharges from 33% (5 of 15) and 25% (5 of 20) of the units tested, respectively. 6. The unmyelinated units had similar mechanical, chemical, and thermal sensitivities. These similarities and the observed convergence only allowed separation of units by the tissue in which the ending was found, and did not allow further classification. 7. The prevalence of background discharge suggested that many units were sensitized during the experiments. 8. The sensitivities of these paraspinal units were similar to those reported for other tissues. Because of the anatomic similarity of the paraspinal tissues of the proximal tail and the lumbar spine, the conclusions of the present study can be related to the lumbar spine. These afferent units are thought to participate in nociception from the deep paraspinal tissues.

Reception of low-intensity millimeter-wave electromagnetic radiation by the electroreceptors in skates.

Low intensity millimeter-wave electromagnetic radiation of less than 10 mW cm-2 power intensity has a nonthermal effect on the body and it is widely used in medical practice for treatment of various diseases. Nevertheless, the effect of EMR on biological tissues is not understood. The skin and its sensory receptors are considered to be responsible for EMR reception, but this has yet to be confirmed. The present experiments were designed to study the effect of millimeter-wave electromagnetic radiation on the ampullae of Lorenzini in skates, which are very sensitive to weak electrical stimuli at low frequency. Reception of low-intensity millimeter-wave electromagnetic radiation at 37-55 GHz by the electroreceptors (ampullae of Lorenzini) in the skate has been shown. At a power intensity of 1-5 mW cm-2 irradiating the duct opening at 1-20 mm distance caused a transient increase in the firing rate of a single afferent unit. When the power intensity was increased inhibitory responses were also observed. Some receptors responded with a prolonged excitatory activity lasting up to 30 min to the irradiation of the duct opening. Direct irradiation of the sensory cells produced only an inhibition, probably due to a rise in temperature. It is proposed that millimeter-wave electromagnetic radiation generates a d.c. potential at the vicinity of duct opening which can be detected by the electroreceptors.

Somatostatin-like immunoreactivity in primary afferents of the medial articular nerve and colocalization with substance P in the cat.

The proportion of somatostatin-containing dorsal root ganglion cells innervating the knee joint of the cat via the medial articular nerve was determined by using retrograde labeling with fast blue and immunohistochemistry. Immunoreactivity was found in 8.6% of labeled cell bodies. In colchicine-treated ganglia, the proportion increased to 16.8%. Only small and intermediate-sized perikarya showed somatostatin-like immunoreactivity, indicating that this neuropeptide is synthesized predominantly in primary afferent units with unmyelinated sensory axons but may also be present in primary afferents with thinly myelinated sensory fibers. Colchicine treatment had no influence on the cell size distribution. Colocalization of somatostatin with substance P was determined by comparing the proportions of immunopositive dorsal root ganglion cells after incubation with antibodies against substance P or somatostatin or with a mixture of both. Substance P-like immunoreactivity was found in 18.1% (untreated ganglia) and 19.6% (colchicine treated ganglia) of the labeled neurons. After incubation with a mixed antibody solution, 18.2% of joint afferents in untreated and 19.9% of the cells in colchicine-treated ganglia were immunopositive. Comparing this result with the results obtained using somatostatin and substance P antibodies alone, one can calculate that both neuropeptides are colocalized in about 17% of the cat's knee joint afferents. About 3% of the neurons contain only substance P, whereas almost none of the neurons contain only somatostatin. Based on this fact, one can assume that both neuropeptides are coreleased in peripheral tissue as well as in the central nervous system.

Centrifugal gastric vagal afferent unit activities: another source of gastric “efferent” control

Our previous studies indicated that in rats about 10% of ventral gastric vagal efferent discharges do not originate from supracervical neural elements. To determine the origin of these efferent activities, an in vitro subdiaphragmatic vagus nerve-esophagus preparation was used. Action potentials with the same amplitude and waveform, and behaving ‘all or none’ characteristic are considered to be recorded from a nerve fiber and defined as an unit activity. Because these centrifugal unit activities were recorded from the proximal cut end of the ventral gastric vagal strands, they are ostensibly considered to be efferent activities. However, about 50% of unit action potential samples (21 out of 40) behave like unit activities recorded from mechanoreceptive afferent fibers. They have spot-like or diffuse mechanoreceptive fields on the subdiaphragmatic esophagus. When these receptive fields were stimulated the sensory nerve terminals in the fields generate afferent unit action potentials. These afferent potentials not only propagate orthodromically to the central nerve system, but also can be transmitted centrifugally to the gastric branches of the same vagal afferent neuron. Together with the efferent discharges of gastric vagal motor neurons, these centrifugal sensory potentials can be intercepted from the proximal cut end of gastric vagal nerve strands at gastroesophageal junction. Three types of mechanoresponsive centrifugal afferent unit activities were observed: rapidly adapting ( n = 8), with or without after-discharge; slowly adapting ( n = 8), with or without after-discharge, and initial high frequency followed by a plateau, with long-lasting after-discharge ( n = 5). Of the tested units ( n = 24), 25% were either activated or inhibited by esophageal inflation and 23% ( n = 22) by esophageal deflation. It is evident that not all centrifugal unit action potentials recorded from the proximal cut end of gastric vagal nerve strands are generated from the vagal motor neurons, the recorded centrifugal unit activities may contain antidromic unit action potentials generated from the esophageal collateral branches of the gastric vagal afferent nerve fibers. These results suggest that gastric vagal afferent neurons possess collateral branches innervating the esophagus, activation of esophageal terminals may exert an effect on the gastric terminals via collateral reflex, analogous to the ‘axon reflex’ mechanism.

The classification and properties of nociceptive afferent units from the skin of the anaesthetized pig.

The afferent properties of nerve fibres innervating the hairy skin of the pig hind limb were investigated by recording from 142 single units from the saphenous nerve. Identified single units were isolated using maximal electrical stimulation of the nerve trunk. Afferent units were classified on the basis of their responses to a range of stimuli, both thermal (heating to 60 degrees C and cooling to 10 degrees C) and mechanical (air jet, von Frey type filaments with forces of 0.1-250 mN, and strong pressure with a blunt needle). A-fibre units (conduction velocity 6.3-64 m/s, n = 60) fell into categories that have been described in hairy skin in other mammalian species. Most were mechanoreceptors, although seven typical A-fibre mechanical nociceptors with large, multipoint fields were also isolated. No cutaneous receptive field could be found for 15% of A-fibre units. Out of 62 C-fibre units (conduction velocity 0.49-2 m/s) 40% had no cutaneous field for pressure, heat or cold. Of the C-fibre units with cutaneous fields, 42% were polymodal nociceptors, 38% were mechanoreceptors with a variety of properties, including some excited by noxious heat, and 19% were heat-only nociceptors. C-polymodal nociceptors had large receptive fields up to 12.5 mm across and did not sensitize following strong heating. Twenty units conducted at 2-6.3 m/s, between the main C- and A-fibre bands, and were varied in their responses. Some had properties identical to C-fibre mechanoreceptors whilst four were sensitive cold thermoreceptors and one was a polymodal nociceptor. Two units were mechanical nociceptors with small receptive fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Hysteresis reduction in proprioception using presynaptic shunting inhibition

1. The tonic responses of angular-position-sensitive afferents in the metathoracic chordotonal organ of the locust leg exhibit much hysteresis. For a given joint angle, the ratio of an afferent's tonic firing rate after extension to its firing rate after flexion (or vice versa) is typically between 1.2:1 and 3:1 but can be as large as 10:1. Spiking local interneurons, that receive direct inputs from these afferents, can, by contrast, exhibit much less hysteresis (between 1.1:1 and 1.2:1). We tested the hypothesis that presynaptic inhibitory interactions between afferent axons reduces the hysteresis of postsynaptic interneurons by acting as an automatic gain control mechanism. 2. We used two kinds of neural models to test this hypothesis: 1) an abstract nonspiking neural model in which a multiplicative, shunting term reduced the "firing rate" of the afferent and 2) a more realistic compartmental model in which shunting inhibition presynaptically attenuated the amplitude of the action potentials reaching the afferent terminals. 3. The abstract neural model demonstrated the automatic gain control capability of a network of laterally inhibited afferent units. A postsynaptic unit, which was connected to the competitive network of afferents, coded for joint angle without saturating as the strength of the afferent input increased by two orders of magnitude. This was possible because shunting inhibition exactly balanced the increase in the excitatory input. This compensatory mechanism required the sum of the excitatory and inhibitory conductances to be much larger than the leak conductance. This requirement suggested a graded weighting scheme in which the afferent recruited first (i.e., at a small joint angle) received the largest inhibition from each of the other afferents because of the lack of active neighbors, and the afferent recruited last (i.e., at a large joint angle) received the least inhibition because all the other afferents were active. 4. The compartmental model demonstrated that presynaptic shunting inhibition between afferents could decrease the average synaptic conductance caused by the afferents onto the spiking interneuron, thereby counterbalancing the afferents' large average firing rates after movements in the preferred direction. Therefore the total postsynaptic input per unit time did not differ much between the preferred and nonpreferred directions.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of gastric mechanoreceptor discharge by cholecystokinin in the rat.

The aim of the present study was to investigate electrophysiologically the effect of systemic cholecystokinin (CCK) on the discharge of vagal gastric mechanoreceptors. Twenty-two single vagal afferent fibers were selected for the investigation of responses to intravenous CCK octapeptide (CCK-8) on the basis of a positive response to gastric distension. Resting discharge in these afferent fibers was 1.3 +/- 0.3 impulses.s-1 and increased to 9.2 +/- 0.9 impulses.s-1 during distension (P < 0.0001), CCK (20-100 pmol iv) caused a gastric relaxation of 2.1 +/- 0.2 cmH2O and inhibition of phasic motility. The discharge of 20/22 of vagal tension receptors closely followed the magnitude and time course of the fall in pressure. Mean discharge before and after CCK (50 pmol) was 7 +/- 0.9 and 3.9 +/- 0.8 impulses.s-1, respectively (P < 0.001, n = 22). Both the pressure response and the concomitant changes in afferent discharge were abolished by L-364,718 (1.2 mg/kg iv). Only two afferent units failed to show a decrease in firing following CCK (50 pmol), and at 500 pmol the discharge of these units was augmented. In conclusion, CCK (50 pmol) has predominantly indirect effects on gastric mechanoreceptors, which decrease their firing in association with gastric relaxation.