Substance P release and neurokinin 1 receptor activation in the rat spinal cord increase with the firing frequency of C-fibers

Both the firing frequency of primary afferents and neurokinin 1 receptor (NK1R) internalization in dorsal horn neurons increase with the intensity of noxious stimulus. Accordingly, we studied how the pattern of firing of primary afferent influences NK1R internalization. In rat spinal cord slices, electrical stimulation of the dorsal root evoked NK1R internalization in lamina I neurons by inducing substance P release from primary afferents. The stimulation frequency had pronounced effects on NK1R internalization, which increased up to 100 Hz and then diminished abruptly at 200 Hz. Peptidase inhibitors increased NK1R internalization at frequencies below 30 Hz, indicating that peptidases limit the access of substance P to the receptor at moderate firing rates. NK1R internalization increased with number of pulses at all frequencies, but maximal internalization was substantially lower at 1–10 Hz than at 30 Hz. Pulses organized into bursts produced the same NK1R internalization as sustained 30 Hz stimulation. To determine whether substance P release induced at high stimulation frequencies was from C-fibers, we recorded compound action potentials in the sciatic nerve of anesthetized rats. We observed substantial NK1R internalization when stimulating at intensities evoking a C-elevation, but not at intensities evoking only an Aδ-elevation. Each pulse in trains at frequencies up to 100 Hz evoked a C-elevation, demonstrating that C-fibers can follow these high frequencies. C-elevation amplitudes declined progressively with increasing stimulation frequency, which was likely caused by a combination of factors including temporal dispersion. In conclusion, the instantaneous firing frequency in C-fibers determines the amount of substance P released by noxious stimuli.     

Effects of some different pulse parameters on bladder inhibition and urethral closure during intravaginal electrical stimulation: an experimental study in the cat

Intravaginal electrical stimulation (IVS) was used in the cat to induce bladder inhibition and urethral closure. The purpose of the study was to compare the efficacy of alternating constant-voltage pulses of different durations (0·1, 0·2, 0·5 and 5 ms) with that of chopped alternating pulses, each consisting of a train of five 0·5 ms pulses with 0·5 ms pauses between. The voltage requirement for an equal biological effect was lowest for the 5 ms alternating pulse, whereas the pulse power dissipation was lowest for the 0·1 ms pulse, about 10 per cent of that for the 5 ms pulse. If both voltage requirement and power dissipation are taken into account, the 0·5 ms pulse was considered the most appropriate compromise. The chopped pulse was the least efficient stimulus, since the threshold voltage was comparable to that of the 0·5 ms duration alternating pulse, implying a five times higher power dissipation. For bladder inhibition, the optimal stimulation frequency for alternating pulses was 10 Hz, both in terms of threshold voltage and power consumption. For urethral closure the voltage requirement was lowest at 50 Hz but 20 Hz was preferable in terms of power dissipation for an equal, although submaximal, effect.     

Cross-excitation in dorsal root ganglia of nerve-injured and intact rats

1. Experiments based on teased fiber recording from rat sciatic nerve have shown that a small proportion of primary afferent neurons in intact dorsal root ganglia (DRGs) fire spontaneously. The prevalence of this discharge is substantially increased if the sciatic nerve has been chronically injured. 2. We now show that in most cases this ongoing DRG activity can be augmented by tetanic stimulation of the axons of neighboring neurons, where the active neuron itself has not been stimulated. In addition, some previously silent DRG neurons can be cross-excited by neighbors. This novel form of neuron-to-neuron communication is termed "DRG crossed afterdischarge." Cross-excitation never occurred at fixed latency in response to single stimulus pulses and is therefore not a case of ephaptic cross talk. 3. Crossed afterdischarge occurred only if the spontaneously active neuron and the stimulated neighbors shared the same DRG. It occurred in 83.5% of the spontaneously active neurons sampled that had myelinated (A) axons, but in only 4.4% of spontaneously active neurons with unmyelinated (C) axons. Among initially silent neurons, stimulation of neighbors evoked firing in 3.1% of A-fibers but in no C-fibers. 4. Crossed afterdischarge responses began within 500 ms of stimulation onset (with the use of 50-Hz tetani) and increased in magnitude for about the first 30 s of stimulation, declining thereafter. Intense excitations were often followed by a short period of depression until the original rate of ongoing discharge was restored. 5. The magnitude of crossed afterdischarge responses increased with increasing stimulation frequency until saturation. Minimal responses occurred with the use of tetani of as little as 1 Hz. Maximal responses occurred with the use of 100-200 Hz tetani. 6. The inclusion of C-fibers in the afferent volley produced little if any augmentation of responses. 7. Cross-excitation was demonstrated in DRGs in which many or all peripheral afferent axons were intact and continued to innervate hind limb skin. In these preparations natural cutaneous stimulation was shown to be capable of evoking crossed afterdischarge responses. The most effective stimuli were gentle or firm rubbing of the foot. Noxious pinch, heat, cold, and chemical stimulation was ineffective. 8. DRG crossed afterdischarge is a mechanism whereby sensation in response to peripheral stimulation may be distorted in time, space, and modality. Because its prevalence is much increased after axotomy, it might contribute to neuropathic sensory abnormalities, including pain, in patients with nerve injury.     

Long-term effects of synaptic activation at low frequency on excitability of myenteric AH neurons

Intracellular microelectrodes were used to record the effects of extended periods (1-30 min) of synaptic activation on AH neurons in the myenteric ganglia of the guinea-pig ileum. Low-frequency (1 Hz) stimulation gave rise to a slowly developing, sustained increase in excitability of the neurons associated with depolarization and increased input resistance. The increased excitability lasted for up to 3.5 h following the stimulus period. Successive stimulus trains (1-4 min) elicited successively greater increases in excitability. The neurons went through stages of excitation. Before stimulation, 500-ms depolarizing pulses evoked up to three action potentials (phasic response) and anode break action potentials were not observed. As excitability increased, more action potentials were evoked by depolarization (the responses became tonic), anode break action potentials were observed, prolonged after hyperpolarizing potentials that follow multiple action potentials were diminished and, with substantial depolarization of the neurons, invasion by antidromic action potentials was suppressed. It is concluded that a state of elevated excitability is induced in myenteric AH neurons by synaptic activation at low frequency and that changes in excitability can outlast stimulation by several hours.     

Pulse-to-pulse changes in the frequency of deep brain stimulation affect tremor and modeled neuronal activity

The effectiveness of deep brain stimulation (DBS) in relieving the symptoms of movement disorders is dependent on the average frequency of stimulation. However, no one has yet examined whether the effectiveness of DBS in relieving tremor is dependent on the pulse-to-pulse (instantaneous) frequency of DBS. We examined the effects of paired-pulse thalamic DBS on tremor in subjects with essential tremor and on the firing of model neurons in a biophysically based computational model of DBS. DBS with an average rate of 130 Hz was more effective at reducing tremor when pulses were evenly spaced than when there were large differences between intrapair and interpair pulse intervals. Similar correlations were observed in the firing patterns of model neurons: increasing the difference between the intrapair and interpair intervals rendered model neurons more likely to fire synchronous bursts, more likely to fire irregularly, and less likely to entrain to the stimulus. The tremor responses provide evidence that the pulse-to-pulse frequency of DBS, not just its average rate, plays an important role in DBS function. Modeling results also suggest that effective DBS overrides oscillatory pathological activity and replaces it with more regularized neuronal firing patterns.     

Neural activity in dorsolateral pontine nucleus of alert monkey during ocular following responses.

1. Movements of the visual scene evoke short-latency ocular following responses. To study the neural mediation of the ocular following responses, we investigated neurons in the dorsolateral pontine nucleus (DLPN) of behaving monkeys. The neurons discharged during brief, sudden movements of a large-field visual stimulus, eliciting ocular following. Most of them (100/112) responded to movements of a large-field visual stimulus with directional selectivity. 2. Response amplitude was measured in two components of the neural response: an initial transient component and a late sustained component. Most direction-selective DLPN neurons showed their strongest responses at high stimulus speeds (80-160 degrees/s), whether their response components were initial (63/87, 72%) or sustained (63/87, 72%). The average firing rates of 87 DLPN neurons increased as a linear function of the logarithm of stimulus speed up to 40 degrees/s for both initial and sustained responses. 3. Not only the magnitude but also the latency of the neural and ocular responses were dependent on stimulus speed. The latencies of both neural and ocular responses were inversely related to the stimulus speed. As a result, the time difference between the response latencies for neural and ocular responses did not vary much with changes of stimulus speed. 4. Response latency was measured when a large-field random dot pattern was moved in the preferred direction and at the preferred speed of each neuron. Seventy-three percent (56/77) of the neurons were activated less than 50 ms after the onset of the stimulus motion. In most cases (67/77, 87%), their increase of firing rate started before the eye movements, and 34% of them (26/77) started greater than 10 ms before the eye movements. 5. Blurring of the random dot pattern by interposing a sheet of ground glass increased the latency of both neural responses and eye movements. On the other hand, the blurred images did not change the timing of the effect of blanking the visual scene on the responses of the neurons or eye movements. 6. When a check pattern was used instead of random dots, both neural and ocular responses began to decrease rapidly when the temporal frequency of the visual stimulus exceeded 20 Hz. When the temporal frequency of the visual stimulus approached 40 Hz, the neurons showed a distinctive burst-and-pause firing pattern. The eye movements recorded at the same time showed signs of oscillation, and their temporal patterns were closely correlated to those of the firing rate.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of tactile stimulation pulse characteristics on sensation threshold and power consumption

The psychophysical responses of human subjects to vibratory tactile stimulation of the skin were investigated experimentally. The parameters, of the waveform important to the minimization of power consumed by the tactile array of electromechanical vibrators and the maximization of the skin sensitivity to the stimulus were explored to develop optimum stimulation. Parameters investigated included the amplitude, frequency, and duty cycle of the current waveform used to drive the vibrators as well as the number of pulses per stimulating burst and the recovery time between bursts. Graphical techniques were used to determine, the optimal combination of the parameters which gave a stimulus that excited the skin to above tactile threshold while maintaining at a relative minimum the power required for the stimulus. The optimal stimulation waveform contains a burst of 10 rectangular pulses of 4% duty cycle separated by a period of nonstimulation of 2 s. Such a waveform can elicit a sensitivity of 29.4 mA⁻¹ consuming only 55 μW of power.     

Phasic stimulation of the locus coeruleus: Effects on activity in the lateral geniculate nucleus

Neurons in the locus coeruleus (LC) encode information related to behavioral state in a tonic pattern of firing and information related to the occurrence of a sensory stimulus in a phasic pattern of firing. The effects of phasic stimulation of the LC (6 pulses at 30 Hz), designed to approximate its physiological activation by sensory stimuli, were studied in the lateral geniculate nucleus (LGN) of anesthetized rats. Phasic stimulation of the LC significantly increased neuronal firing in the LGN with a mean latency 320 ms from onset of stimulation. Receiver operating characteristic analyses on a trial-by-trial basis showed that phasic LC stimulation can result in a highly discriminable signal in the LGN. This increased neuronal firing rate in the LGN was specific for the site of stimulation and was reduced by the norepinephrine synthesis inhibitor αmethyl-p-tyrosine and by intravenous WB-4101 (α₁-receptor antagonist). Neurons in the LGN have a singlespike firing mode when sensory information is faithfully relayed from retina to cortex and a burst-firing mode when the transfer of this information is degraded. Phasic LC stimulation reduced burst firing (2–5 ms interspike intervals, ISIs) at low frequencies ( ≤4 Hz) in the LGN, and for some neurons there was an absolute decrease in burst-like ISIs after LC stimulation, despite an increase in mean firing rate.     

Effects of midbrain stimulation and iontophoretic application of serotonin, noradrenaline, morphine and GABA on electrical thresholds of afferent C- and A-fibre terminals in cat spinal cord

We have used the single-fibre excitability testing method to investigate whether electrical stimulation in midbrain periaqueductal gray or lateral reticular formation, as well as intraspinal iontophoretic application of the suspected inhibitory neurotransmitters serotonin (5-hydroxytryptamine), noradrenaline, the opiate morphine, or gamma-aminobutyric acid (GABA), exert presynaptic actions at the central terminals of cutaneous afferent unmyelinated or myelinated fibres. Thresholds to antidromically excited 42 single unmyelinated and 18 myelinated fibres in the sural nerve by intraspinal microstimulation were determined before and during periaqueductal gray or lateral reticular formation stimulation (3 100 ms trains/s at 100 Hz; 100-900 microA) or intraspinal iontophoretic application (40-300 nA) of 5-hydroxytryptamine, noradrenaline, morphine or GABA from a multibarrel micropipette. Periaqueductal gray or lateral reticular formation stimulation had mixed effects on unmyelinated and myelinated fibre thresholds, with most threshold measurements within +/- 10% of control. There was a tendency for thresholds to increase more during periaqueductal gray than lateral reticular formation stimulation. Thresholds of unmyelinated fibres were predominantly raised during iontophoretic application of 5-hydroxytryptamine (20/29 fibres), noradrenaline (10/13) and morphine (15/21), while GABA had mixed effects; thresholds of nearly all myelinated fibres were raised by each drug. Both periaqueductal gray or lateral reticular formation stimulation and application of 5-hydroxytryptamine, noradrenaline or morphine tended to raise thresholds in the majority of the 53 unmyelinated and myelinated fibres tested. Methodological problems in interpreting the physiological significance of these results for presynaptic modulation are discussed.     

Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig

The main objective of this study was to determine whether bone-conducted vibration (BCV) is equally effective in activating both semicircular canal and otolith afferents in the guinea pig or whether there is preferential activation of one of these classes of vestibular afferents. To answer this question a large number (346) of single primary vestibular neurons were recorded extracellularly in anesthetized guinea pigs and were identified by their location in the vestibular nerve and classed as regular or irregular on the basis of the variability of their spontaneous discharge. If a neuron responded to angular acceleration it was classed as a semicircular canal neuron, if it responded to maintained roll or pitch tilts it was classified as an otolith neuron. Each neuron was then tested by BCV stimuli—either clicks, continuous pure tones (200–1,500 Hz) or short tone bursts (500 Hz lasting 7 ms)—delivered by a B-71 clinical bone-conduction oscillator cemented to the guinea pig's skull. All stimulus intensities were referred to that animal's own auditory brainstem response (ABR) threshold to BCV clicks, and the maximum intensity used was within the animal's physiological range and was usually around 70 dB above BCV threshold. In addition two sensitive single axis linear accelerometers cemented to the skull gave absolute values of the stimulus acceleration in the rostro-caudal direction. The criterion for a neuron being classed as activated was an audible, stimulus-locked increase in firing rate (a 10% change was easily detectable) in response to the BCV stimulus. At the stimulus levels used in this study, semicircular canal neurons, both regular and irregular, were insensitive to BCV stimuli and very few responded: only nine of 189 semicircular canal neurons tested (4.7%) showed a detectable increase in firing in response to BCV stimuli up to the maximum 2 V peak-to-peak level we delivered to the B-71 oscillator (which produced a peak-to-peak skull acceleration of around 6–8 g and was usually around 60–70 dB above the animal's own ABR threshold for BCV clicks). Regular otolithic afferents likewise had a poor response; only 14 of 99 tested (14.1%) showed any increase in firing rate up to the maximum BCV stimulus level. However, most irregular otolithic afferents (82.8%) showed a clear increase in firing rate in response to BCV stimuli: of the 58 irregular otolith neurons tested, 48 were activated, with some being activated at very low intensities (only about 10 dB above the animal's ABR threshold to BCV clicks). Most of the activated otolith afferents were in the superior division of the vestibular nerve and were probably utricular afferents. That was confirmed by evidence using juxtacellular injection of neurobiotin near BCV activated neurons to trace their site of origin to the utricular macula. We conclude there is a very clear preference for irregular otolith afferents to be activated selectively by BCV stimuli at low stimulus levels and that BCV stimuli activate some utricular irregular afferent neurons. The BCV generates compressional and shear waves, which travel through the skull and constitute head accelerations, which are sufficient to stimulate the most sensitive otolithic receptor cells.     

Discharge patterns of somatosensitive neurons in the nucleus tractus solitarius of the cat

Encoding of sensory information by nucleus of the solitary tract (NTS) neurons is incompletely understood. Using extracellular single-unit recording in alpha-chloralose-urethane anesthetized cats, we have examined the discharge characteristics of NTS neurons to activation of somatic Adelta and C fiber afferents by skeletal muscle contraction evoked by electrical stimulation of lower lumbar/upper sacral ventral roots. Generally, somatic afferent stimulation evoked two distinct firing patterns. The first population (36/43 cells) increased their firing rate to brief somatic stimuli. A subset (21/27 cells) exhibited a rapid decay of their firing rate during sustained somatic stimulation. Peak instantaneous firing frequency (F(p)) increased proportionally with the intensity of somatic stimulation (105+/-4 vs. 119+/-4 vs. 139+/-4 Hz, 10, 20 and 40 Hz, respectively, P<0.0001), whereas steady-state firing frequency (F(ss)) was not altered (25+/-2 vs. 27+/-2 vs. 27+/-2 Hz, 10, 20 and 40 Hz, respectively, P=0.72). Two indices were derived to quantify the decay properties. The decay rate constant (obtained from exponential curve fitting) was not altered by stimulation frequency (461+/-10 vs. 442+/-14 vs. 429+/-26 ms, 10, 20 and 40 Hz, respectively, P=0.415), nor was the decay index (derived to express the percent reduction in firing rate with respect to the initial peak firing rate; 76+/-2 vs. 77+/-2 vs. 81+/-2%, 10, 20 and 40 Hz, respectively, P=0.187). In contrast, the second population (seven of 43 cells) decreased their firing rate to stimulation. Of the NTS neurons tested for barosensitivity (29/36), none responded to pressure stimulation. These results have identified a population of somatosensitive NTS neurons that exhibit rapid firing rate decay properties during sustained stimulation. However, this population could faithfully encode phasic excitation during rhythmic somatosensory input. These results are discussed in relation to the role of somatosensory input on baroreflex function.     

Sensory encoding in Neuregulin 1 mutants

Schizophrenic patients show altered sensory perception as well as changes in electrical and magnetic brain responses to sustained, frequency-modulated sensory stimulation. Both the amplitude and temporal precision of the neural responses differ in patients as compared to control subjects, and these changes are most pronounced for stimulation at gamma frequencies (20–40 Hz). In addition, patients display enhanced spontaneous gamma oscillations, which has been interpreted as ‘neural noise’ that may interfere with normal stimulus processing. To investigate electrophysiological markers of aberrant sensory processing in a model of schizophrenia, we recorded neuronal activity in primary somatosensory cortex of mice heterozygous for the schizophrenia susceptibility gene Neuregulin 1. Sensory responses to sustained 20–70 Hz whisker stimulation were analyzed with respect to firing rates, spike precision (phase locking) and gamma oscillations, and compared to baseline conditions. The mutants displayed elevated spontaneous firing rates, a reduced gain in sensory-evoked spiking and gamma activity, and reduced spike precision of 20–40 Hz responses. These findings present the first in vivo evidence of the linkage between a genetic marker and altered stimulus encoding, thus suggesting a novel electrophysiological endophenotype of schizophrenia.     

Control of firing by small (S)-alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid-like inputs in hypothalamic gonadotropin releasing-hormone (GnRH) neurons

Episodic release of gonadotropin releasing hormone (GnRH) is obligatory for mammalian reproduction. The contribution of synaptic input to intermittent firing of GnRH neurons is unclear. GnRH neurons have very few synapses and most post-synaptic currents are small. Therefore, the impact of synaptic currents on firing in GnRH neurons was directly examined using simulated (S)-alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA)-like inputs applied with the method of dynamic current clamping. Tightly synchronized inputs and 50 ms bursts of excitatory input resulted in action potentials that were coincident with the stimulus. Neither input pattern resulted in sustained firing. When ongoing patterns of simulated inputs were applied over a range of parameters, action potentials were associated with clusters of AMPA-like inputs of 250 pS (approximately 15 pA amplitudes), while single inputs of 500 pS (approximately 30 pA amplitudes) resulted in action potentials. Ongoing inputs of 500 pS drove firing at 4-9 Hz. These findings provide evidence that small, simulated glutamatergic inputs can control firing in GnRH neurons and suggest that despite the small amplitudes, endogenous synaptic input mediated by glutamate may contribute to firing in GnRH neurons.     

Re-Evaluation of Muscle Wisdom in the Human Adductor Pollicis using Physiological Rates of Stimulation

Motor unit discharge rates decline by about 50 % over 60 s of a sustained maximum voluntary contraction (MVC). It has been suggested that this decline in discharge rate serves to maintain force by protecting against conduction failure and by optimizing the input to motor units as their contractile properties change. This hypothesis, known as muscle wisdom, is based in part on studies in which muscle force was shown to decline more rapidly when stimulation was maintained at a high rate than when stimulus rate was reduced over time. The stimulus rates used in those studies, however, were higher than those normally encountered during MVCs. The purpose of this study was to compare force loss under constant and declining stimulus rate conditions using rates similar to those that occur during voluntary effort. Isometric force and surface EMG signals were recorded from human adductor pollicis muscles in response to supramaximal stimuli delivered to the ulnar nerve at the elbow. Three fatigue protocols, each 60 s in duration, were carried out on separate days on each of 10 subjects: (1) continuous stimulation at 30 Hz, (2) stimulation at progressively decreasing rates from 30 to 15 Hz and (3) sustained MVC. The relative force–time integral (endurance index) was significantly smaller for the sustained MVC (0.75 ± 0.08) and decreasing stimulus rate conditions (0.76 ± 0.16) compared to the condition in which stimulus rate was maintained at 30 Hz (0.90 ± 0.13). These findings suggest that decreases in discharge rate may contribute to force decline during a sustained MVC.     

Processing of periodic whisker deflections by neurons in the ventroposterior medial and thalamic reticular nuclei

Rats employ rhythmic whisker movements to sample information in their sensory environment. To study frequency tuning and filtering characteristics of thalamic circuitry, we recorded single-unit responses of ventroposterior medial (VPm) and thalamic reticular (Rt) neurons to 1- to 40-Hz sinusoidal and pulsatile whisker deflection in lightly narcotized rats. Neuronal entrainment was assessed by a measure of the relative modulation (RM) of firing at the stimulus frequency given by the first harmonic (F1) of the cycle time histogram divided by the mean firing rate (F0). VPm signaling of both sinusoidal and periodic pulsatile whisker movements improved gradually over 1-16 and was maximal at 20-40 Hz. By contrast, the RM of Rt responses increased over 1-8 Hz, but deteriorated progressively over the 12- to 40-Hz range. In Rt, response adaptation occurred at lower stimulus frequencies and to a greater extent than in VPm. Within a train of high-frequency stimuli, Rt responses progressively decremented, possibly due to the accumulation of inhibition, whereas those of VPm neurons augmented. Mean firing rates in Rt increased 42 spikes/s over 1-40 Hz, providing tonic (low RM) inhibition during high-frequency stimulation that may enhance VPm signal-to-noise ratios. Consistent with this view, VPm mean firing rates increased only 13 spikes/s over 1-40 Hz, and inter-deflection activity was suppressed to a greater extent than stimulus-evoked responses. Rt inhibition is likely to act in concert with actions of neuromodulators in optimizing thalamic temporal signaling of high-frequency whisker movements.     

Vestibular primary afferent responses to sound and vibration in the guinea pig

This study tested whether air-conducted sound and bone-conducted vibration activated primary vestibular afferent neurons and whether, at low levels, such stimuli are specific to particular vestibular sense organs. In response to 500 Hz bone-conducted vibration or 500 Hz air-conducted sound, primary vestibular afferent neurons in the guinea pig fall into one of two categories--some neurons show no measurable change in firing up to 2 g peak-to-peak or 140 dB SPL. These are semicircular canal neurons (regular or irregular) and regular otolith neurons. In sharp contrast, otolith irregular neurons show high sensitivity: a steep increase in firing as stimulus intensity is increased. These sensitive neurons typically, but not invariably, were activated by both bone-conducted vibration and air-conducted sound, they originate from both the utricular and saccular maculae, and their sensitivity underpins new clinical tests of otolith function.     

Intensity and frequency characteristics of pacinian corpuscles. II. Receptor potentials

Intensity characteristics that relate receptor- (generator) potential amplitude to vibration amplitude and frequency characteristics that relate either the stimulus intensity required for a criterion response or the phase angle between the stimulus and the receptor potential to vibration frequency have been obtained from isolated pacinian corpuscles removed from cat mesentery. The intensity characteristics of signal-averaged receptor potentials in response to sinusoidal displacements were found to be linear at low stimulus levels and to saturate at higher ones. At the higher levels, an asymmetric full-wave rectification was often found, the degree of which varied among receptors. The receptor-potential waveforms showed a time-dependent hysteresis in response to every stimulus cycle at moderate and high stimulus levels. An average intensity characteristic is given. The measured amplitude-frequency characteristics for a constant magnitude of the receptor potential below the neural spike threshold were found to be U-shaped functions. The averaged (n = 7) amplitude-frequency characteristic generated at a constant criterion response had a best frequency of 370 Hz and a bandwidth of Q3 dB equal to 0.8. The phase-frequency characteristics of the receptor potentials below spike threshold exhibited two populations of responses. Both populations underwent phase changes of about 300 degrees as the vibration frequency was increased from 20 Hz to 1.0 kHz but were separated by 180 degrees. An average (n = 8) phase-frequency characteristic is shown. For a constant neural firing rate, the relationship between receptor-potential amplitude and stimulus frequency was also U-shaped. Several qualitative physiological models are presented in relation to previously reported anatomical evidence (14, 18, 19, 32, 45). For the intensity domain, it is suggested that the cytoplasmic extensions that protrude from the unmyelinated portion of the corpuscle axon into the hemilamellar clefts are responsible for the asymmetric full-wave rectification and the response polarity in the phase-frequency characteristics. It is the asymmetric full-wave rectification and consequent receptor-potential waveforms that produce the 2 spikes/stimulus cycle plateaus in the characteristics relating firing rate to stimulus intensity described in the preceding paper (5). An additional model, based on the recovery of spike threshold, suggests how the plateaus in the firing rate-intensity characteristics (5) are produced. For the frequency domain, three filters in cascade can account for the frequency characteristic obtained with a constant firing rate criterion (see Ref. 5).(ABSTRACT TRUNCATED AT 400 WORDS)     

Stimulation of a myelinated nerve axon by electromagnetic induction

A model of electromagnetic stimulation predicts the transmembrane potential distribution along a myelinated nerve axon and the volume of stimulated tissue within a limb. Threshold stimulus stregth is shown to be inversely proportional to the square of the axon diameter. It is inversely proportional to pulse duration for short pulses and independent of pulse duration for long ones. These results are also predicted by dimensional analysis. Two dimensionless numbers, S_em, the ratio of the induced transmembrane potential to the axon's threshold potential, and T_c/T, the ratio of the pulse duration to the membrane time constant, summarise the dependence of threshold stimulus strength on pulse duration and axon diameter.     

Effects of conditioning stimulation of the central amygdaloid nucleus on tooth pulp-driven neurons in the cat somatosensory cortex (SI)

To study the limbic control of nociception, we examined the effect of conditioning stimulation of the central amygdaloid nucleus (ACE) on tooth pulp-driven (TPD) neurons in the first somatosensory cortex (SI). Cats were anesthetized with N(2)O-O(2) (2:1) and 0.5% halothane, and immobilized with tubocurarine chloride. The tooth pulp test stimulus was applied by a single rectangular pulse (0.5 ms in duration and 3-5 times the threshold intensity for the jaw-opening reflex). Conditioning stimuli to the ACE consisted of trains of 33 pulses (300 microA) delivered at 330 Hz at intervals of 8-10 s. In 35 out of 61 of the slow (S)-type TPD neurons with latencies of more than 20 ms, conditioning stimulation in the ACE, especially in the medial division, markedly reduced the firing response to the pulpal stimulation. The inhibition of the firing rate in the S-type neurons was 74% of the control. In these S-type neurons, the neurons that were inhibited had significantly longer latencies compared to the non-inhibited neurons (45.0 +/- 17.6 ms, n = 32 vs. 34.8 +/- 10.5 ms, n = 26). In contrast, the ACE conditioning stimulation affected only one out of 18 fast-type TPD neurons with latencies of less than 20 ms. In addition, ACE stimulation had no effect on the spontaneous discharges of either S-type or F-type neurons. The ACE inhibitory effect on S-type neurons was not diminished by naloxone administration (1 mg/kg, I.V. ), while the blockade of histamine H(1)-receptor by diphenhydramine hydrochloride (0.5 mg/kg, I.V.) partially reversed the inhibitory effect. These results suggest that the ACE inhibits ascending nociceptive information to the SI and that this inhibition is mediated in part by histamine (H(1)) receptors. It seems likely that the antinociceptive effect is a neurophysiological basis for stress-induced analgesia (SIA).     

Rhythmic neuronal interactions and synchronization in the rat dorsal column nuclei

Single-unit and multiunit activities were recorded from dorsal column nuclei of anesthetized rats in order to study the characteristics of the oscillatory activity expressed by these cells and their neuronal interactions. On the basis of their firing rate characteristics in spontaneous conditions, two types of dorsal column nuclei cell have been identified. Low-frequency cells (74%) were silent or displayed a low firing rate (1.9+/-0.48 spikes/s), and were identified as thalamic-projecting neurons because they were activated antidromically by medial lemniscus stimulation. High-frequency cells (26%) were characterized by higher discharge rates (27.2+/-5.1 spikes/s). None of them was antidromically activated by medial lemniscus stimulation. Low-frequency neurons showed a non-rhythmic discharge pattern spontaneously which became rhythmic under sensory stimulation of their receptive fields (48% of cases; 4.8+/-0.23Hz). All high-frequency neurons showed a rhythmic discharge pattern at 13.8+/- 0.68Hz either spontaneously or during sensory stimulation of their receptive fields. The shift predictor analysis indicated that oscillatory activity is not phase-locked to the stimulus onset in either type of cell, although the stimulus can reset the phase of the rhythmic activity of high-frequency cells. Cross-correlograms between pairs of low-frequency neurons typically revealed synchronized rhythmic activity when the overlapping receptive fields were stimulated. Rhythmic synchronization of high-frequency discharges was rarely observed spontaneously or under sensory stimulation. High-frequency neuronal firing could be correlated with the low-frequency neuronal activity or more often with the multiunit activity during sensory stimulation. Moreover, the presence of oscillatory activity modulated the sensory responses of dorsal column nuclei cells, favoring their responses.These findings indicate that thalamic-projecting and non-projecting neurons in dorsal column nuclei exhibited distinct oscillatory characteristics. However, both types of neuron may be entrained into an oscillatory rhythmic pattern when their overlapping receptive fields are stimulated, suggesting that in those conditions the dorsal column nuclei generate a populational oscillatory output to the somatosensory thalamus which could modulate and amplify the effectiveness of the somatosensory transmission.