Successive Spikes Research Articles

Abnormal discharge originates at the site of nerve injury in experimental constriction neuropathy (CCI) in the rat

Rats with an experimental painful peripheral neuropathy created by placing loosely constrictive ligatures around the sciatic nerve (the CCI model) display heat-hyperalgesia on the affected limb. Pain threshold was studied using the paw withdrawal method. Electrophysiological recording from myelinated primary afferent axons revealed spontaneous impulse activity which originated at the site of nerve constriction. Overall 10.1 ± 1.5% of the fibers sampled had spontaneous activity during the period 2–14 days post injury. The spontaneous activity fell into three patterns: (1) ‘tonic’ rhythmic pattern, in which the interval between successive spikes in a train was uniform, ranging from 25–50 ms (discharge rate 20–40 Hz); (2) interrupted, bursty or ‘on-off’ pattern, with variable silent period between high frequency bursts; and (3) ‘irregular’ ongoing pattern with random inter-spike intervals (5–15 Hz). There was a correlation between the prevalence and pattern of spontaneous activity, and the development of hyperalgesia post-injury. Axons trapped at the injury site including ones with and without spontaneous activity, became hyperexcitable to mechanical stimulation. The location of mechanosensitive spots progressively shifted over the period 2–14 days from the proximal to the distal part of the injury site. The spontaneous discharge of injured primary afferent fibers may contribute to abnormal sensation in these animals.

Reliability and statistical efficiency of a blowfly movement-sensitive neuron

We develop model-independent methods for characterizing the reliability of neural spike trains in response to brief stimuli. Through this approach we measure the discriminability of similar stimuli based on the real-time response of a single neuron in much the same way that modern psychophysical techniques measure the discrimination performance of the whole animal. Extending these techniques, we quantify discriminability as a function of time after stimulus presentation, so that it is possible to compare the measured reliability of the neuron to its theoretical limit predicted from signal transduction and noise levels in the sensory periphery. The methods are applied to a wide-field movement-sensitive neuron (HI) in the visual system of the blowfly Calliphora vicina , where we also record from the photoreceptor cells that provide the sensory input to HI. From an analysis of neural responses to wide-field stepwise movements of various step sizes we find the following. (1) One or two spikes are sufficient to encode just noticeable differences of approximately one-tenth the angular spacing between photoreceptors, comparable to the hyperacuity regime observed in humans. (2) Discriminability improves upon observation of successive spikes as if the interspike intervals carried independent information. Coding seems orderly and analogue in the sense that we find no indication of information being transmitted in complex combinations of spike intervals. (3) As a result of neural refractoriness the real neuron’s performance is significantly better than that of a neuron generating spikes according to a Poisson process at the same firing rate. (4) Over behaviourally relevant time intervals following the movement step, that is up to about 30-40 ms, the discrimination performance of the neuron is close to that of an ideal observer who extracts movement information from all the photoreceptor cells in the field of stimulation. Beyond this time the neuron's performance relative to the ideal observer decreases significantly.

Experimental Observations of Thermal Spikes in Microwave Processing of Ceramic Oxide Fibers

ABSTRACTMicrowave heating of alumina/silica fiber tows in a single-mode microwave cavity at 2.45 GHz has produced a surprising thermal spike behavior on the fiber bundles. During a thermal spike, a “hot spot” on the tow brightens rapidly, persists for a few seconds, and then rapidly extinguishes. A hot spot can encompass the entire tow in the cavity or just a localized portion of the tow. Some local hot spots propagate along the fiber. Thermal spikes are triggered by relatively small (<15%) increases in power, thus having obvious implications for the development of practical microwave fiber processing systems. A tow can be heated through several successive thermal spikes, after which the tow is left substantially cooler than it was originally, although the applied microwave electric field is much larger. X-ray diffraction studies show that after each temperature spike there is a partial phase transformation of the tow material into mullite. After several excursions the tow has been largely transformed to the new, less lossy phase and is more difficult to heat. Heating experiments with Nextel 550 tows are examined for a plausible explanation of this microwave heating behavior.

Mechanisms underlying burst generation of the pyloric muscle in the mantis, shrimp, Squilla oratoria

The pyloric constrictor muscles of the stomach in Squilla can generate spikes by synaptic activation via the motor nerve from the stomatogastric ganglion. Spikes are followed by slow depolarizing afterpotentials (DAPs) which lead to sustained depolarization during a burst of spikes. 1. The frequency of rhythmic bursts induced by continuous depolarization is membrane voltage-dependent. A brief depolarizing or hyperpolarizing pulse can trigger or terminate bursts, respectively, in a threshold-dependent manner. 2. The conductance increases during the DAP response. The amplitude of DAP decreases by imposed depolarization, whereas it increases by hyperpolarization. DAPs from successive spikes sum to produce a sustained depolarizing potential capable of firing a burst. 3. The spike and DAP are reduced in amplitude by decreasing [Ca]o, enhanced by Sr2+ or Ba2+ substituted for Ca2+, and blocked by Co2+ or Mn2+. DAPs are selectively blocked by Ni2+, and the spike is followed by a hyperpolarizing afterpotential. 4. The spike and DAP are prolonged by intracellular injection of the Ca2+ chelator EGTA. A hyperpolarizing afterpotential is abolished by EGTA and enhanced by increasing [Ca]o. The DAP is diminished in Na(+)-free saline and reduced by tetrodotoxin. 5. It is concluded that the muscle fiber is endowed with endogenous oscillatory properties and that the oscillatory membrane events result from changes of a voltage- and time-dependent conductance to Ca2+ and Na+ and a Ca2+ activated conductance to K+.

First order temporal properties of spontaneous and tone-evoked activity of auditory afferent neurones in the cochlear ganglion of the pigeon

Spontaneous and tone-evoked single-unit activity was recorded from afferent neurones in the cochlear ganglion of the anaesthetized pigeon, and the data analysed in a way that allowed the physics of underlying mechanisms to be described. The periodicity of neural activity was quantified by Fourier analysis of the histogram of successive spike intervals. Spontaneous activity was quasiperiodic for 57% of neurones (average rate: 74 s −1); it was irregular for the remainder of neurones (average rate: 55 s −1). The preferred frequency (PF) of the quasiperiodic spontaneous activity was, on average, equal to the characteristic frequency (CF) of the neurone (70% of cases) or CF/2 (30%). This observation can be explained by supposing that preferred intervals of spontaneous activity are generated by noise passing through a filter tuned to the CF of the neurone; in most cases (70%) discharge was synchronized to CF, but in the others the neurone fired to every second cycle of the filtered signal. Consistent with this interpretation, for 79% of neurones, the modal interval of spontaneous activity was, on average, directly proportional to the CF-period, irrespective of whether preferred intervals were detected. The synchronization index at the PF was inversely related to the PF, and was quantified by the amplitude response of a first-order low-pass filter with cutoff frequency of 48 ± 18 Hz. The spontaneous activity of 9% of neurones exhibited a second-harmonic component of the PF. For both tone-evoked and spontaneous activity, the observed synchronization indices of harmonics of the stimulus frequency or of the PF were consistent with an underlying exponential spike-generator function. If such a function does indeed govern spike generation, then it implies that the Shannon entropy of the probability density function of the instantaneous firing rate is near its maximum value and suggests that the system is close to statistical equilibrium. Single-tone rate-suppression was detected for 53% of those neurones that exhibited multiple preferred intervals of spontaneous activity. It is conjectured that the phenomena of quasiperiodic spontaneous activity and single-tone rate-suppression are different aspects of a single presynaptic process. According to this model, we would expect to find these two phenomena in animals that have auditory fibres innervating electrically tuned hair cells, and that have stereocilia firmly coupled to a tectorial membrane.

The activity pattern of phrenic motoneurons during the aspiration reflex: an intracellular study

Membrane potential trajectories and discharge characteristics were measured intracellularly in 29 phrenic motoneurons of anesthetized, paralyzed and artificially ventilated cats during hypercapnic respiration and the aspiration reflex. Fifteen ‘active’ cells discharged spontaneously during inspiration, and the remaining 14 ‘quiescent’ cells exhibited no discharge in spite of strong central respiratory drive. The mean membrane potential of the quiescent cells during inspiration (−62 ± 4 mV) was significantly lower than the threshold level determined for the active cells (−52 ± 4 mV). The mean axonal conduction velocity was slower for the active (60.4 ± 8.7 m/s) than quiescent cells (67.4 ± 6.9 m/s). All phrenic motoneurons discharged during the aspiration reflex with maximum instantaneous frequencies ranging from 6 to 357 Hz. No differences were found for the maximum discharge frequency during the reflex between the active and quiescent cells. Although there were differences in the slopes of the depolarization during inspiration between the groups of cells, no such difference existed in the slopes during the aspiration reflex. The threshold level for the first spike during the reflex was the same as that during inspiration but the level for successive spikes became progressively less negative while spike amplitude decreased and duration increased. Stimulation of the nasopharynx to elicit the aspiration reflex was found to alter the timing of the subsequent respiratory cycles.

HREM investigation of GeV heavy ion latent tracks in ferrites

The irradiation of ferrites Bi 2Fe 4O 9, Y 3Fe 5O 12, BaFe 12O 19 and AFe 2O 4 (A = Fe, Zn, Ni, Mg) by 3.0 GeV xenon ions creates paramagnetic cylinders of nearly amorphous matter around the path of the ion. The latent tracks are continuous for Bi 2Fe 4O 9, Y 3Fe 5O 12, BaFe 12O 19, NiFe 2O 4 and MgFe 2O 4 and discontinuous for Fe 3O 4 and ZnFe 2O 4 emphasizing the existence of a threshold energy deposition. Track production mechanism based on Coulomb explosion spike and statistical ion spike concepts is proposed above the threshold. Under the threshold the gap model based on successive ionization spikes could be considered.

Self-stabilization of ultrashort pulses emitted by a neodymium phosphate glass laser

An investigation was made of the emission spectra of a neodymium phosphate glass laser during various stages of formation of ultrashort pulses. The kinetics of the spectrum of free lasing with passive mode locking was observed first. Considerable changes in the spectrum were observed for successive free-lasing spikes, which made it impossible to achieve self-stabilization of the ultrashort pulse duration. The spectrum of ultrashort pulses varied with the point of selection of a pulse in a train. The results were explained allowing for the simultaneous influence of burning of spectral holes in the population inversion and phase self-modulation on the operation of a laser with passive mode locking.

Reduction of the voltage-dependent calcium current in Aplysia neurons by pentobarbital.

Effects of pentobarbital on the calcium current of Aplysia neurons were investigated under current- and voltage-clamp conditions using the conventional two-microelectrode technique. Pentobarbital attenuated the progressive broadening of repeated action potentials of somata, suggesting a reduction in the calcium current. When calcium ion was replaced with barium ion in the perfusing solution, in which neither sodium nor potassium ions carried transmembrane currents, the barium current (IBa) which flowed through the calcium channel of the cell membrane was generated by depolarizing pulses of several hundred milliseconds applied every 1 min from a holding potential of -50 mV. The IBa was not affected by tetrodotoxin (30 microM). The current was decreased by pentobarbital (0.1-5 mM) in a dose-dependent manner. The inhibition was much greater at a lower pH of the perfusate, indicating that the uncharged form of the agent was responsible. The voltage-dependent inactivation of the IBa proceeded with two time constants [190 +/- 21 and 2020 +/- 146 msec (N = 4) at -10 mV], both of which were shortened by adding 1 mM pentobarbital [to 120 +/- 18 and 540 +/- 51 msec (N = 4), respectively]. The IBa recovered from the inactivation with two time constants [60 +/- 7 and 871 +/- 76 msec (N = 3) at -50 mV]. The anesthetic (1 mM) prolonged both of them, to 124 +/- 20 and 1480 +/- 172 msec (N = 3), respectively, resulting in a use-dependent depression of the current at 2-Hz stimulation. Pentobarbital reduced the IBa to a greater extent when the holding potential was more positive (-30 instead of -50 mV), indicating a higher affinity of the drug to the inactivated state of the channel. These findings suggest that the attenuation of the progressive broadening of successive spikes by pentobarbital is due to a decrease in the voltage- and time-dependent calcium current, ending in depression of transmitter release from the nerve terminal.

Conduction velocity and spike duration during afterdischarge in neuroendocrine bag cells of Aplysia.

Changes in conduction velocity and spike duration during electrically triggered afterdischarges were determined with extracellular recordings from bag-cell neurites of Aplysia. Spikes with high conduction velocity and short duration occurred at the onset of the afterdischarge during the period of high-frequency firing and regular interspike intervals. Later in the afterdischarge, spike frequency and conduction velocity decreased, while spike duration increased. During the short bursts within the later part of the afterdischarge, conduction velocity was highest for the first spike and decreased for successive spikes in the burst. That conduction velocity and spike frequency were both maximal during the first minute of the afterdischarge and lower during the later periods of the spike train supports the hypothesis that changes in the excitability of the bag-cell neurites occur during this firing pattern. Furthermore, the slower conduction velocity and longer duration of spikes from the bag-cell neurites late in the afterdischarge, and late in the individual bursts within the afterdischarge, suggest the hypothesis of enhanced hormone release per action potential during these periods.

Soma spike of neuroendocrine bag cells of Aplysia californica.

Soma action potentials of the neuroendocrine bag cells of Aplysia californica were studied with intracellular recording and current injection. Spikes in artificial sea water (ASW) were either graded with increasing depolarizing current pulses, or had a well-defined threshold. The latter spikes typically had faster rise times with larger overshoots and hyperpolarizing afterpotentials. Repetitive stimulation led to spike potentiation (SP), manifested as an increase in overshoot amplitude and duration of successive spikes in a train. SP was usually detectable at 0.5 Hz, and maximal between 0.8 and 4 Hz. Concomitant accommodation occurred rapidly at greater than or equal to 5 Hz. The increase in spike duration during SP resulted from a progressive enhancement of an inflection on the repolarizing phase. The inflection was dependent on membrane potential; small depolarizations (5-10 mV) enhanced it; hyperpolarization (less than 35 mV) reduced it. Solutions with O--Na+ (Tris-substituted) or O--Ca2+ (1 mM EGTA) revealed mixed Na+/Ca2+ spikes with variable degrees of Na+ versus Ca2+ dominance. Cd2+, Co2+, and Mn2+ reversibly abolished the inflection on the repolarizing phase, indicating that it is Ca2+ mediated; the spike was reduced irreversibly at higher concentrations. SP was generally reduced only if the spike was severely attenuated. It is proposed that SP results primarily from a voltage- and time-dependent potassium inactivation which then unmasks a calcium current. SP may play a role in augmenting the release of egg-laying hormone.

Excitability of female rat central gray cells with medullary projections: changes produced by hypothalamic stimulation and estrogen treatment.

1. Effects of estrogen on the excitability of 74 neurons in the central gray of the mesencephalon (CG) antidromically identified from the medulla were investigated extracellularly in female rats under urethan anesthesia. 2. The mean rate of spontaneous discharge of the identified CG cells was higher in estrogen-treated (2.9 Hz) than in untreated ovariectomized rats (0.3 Hz). In the estrogen-treated preparations, 18.5% of the identified cells had discharge rates exceeding 3.0 Hz, while none were found in this range in the untreated animals. 3. Two types of positive-negative biphasic antidromic spike potentials were distinguished. In one ("fast") the initial positive deflection was completed within 500-700 microseconds, while it took longer than 1 ms in the other ("slow" spikes). Slow spikes had a notch in the rising phase of their initial positive deflection, at which antidromic propagation was often blocked. Mean antidromic spike latency for the fast spikes was 6.8 ms, while the value for the slow spikes was 14.7 ms. 4. In slow spikes, the percentage of successful antidromic spike invasions into the somatodendritic complex remained constant for a long time when the response was elicited by repetitive antidromic stimuli at 0.5 Hz. Antidromic propagation into the somatodendritic complex occurred more frequently in the slow spikes recorded from estrogen-treated preparations (94.2%) than in those of ovariectomized untreated animals (55.7%). 5. Electrical stimulation of the preoptic area (POA) reduced the frequency of successful antidromic propagation into the somatodendritic complex. Stimulation of the ventromedial nucleus of the hypothalamus (VMN) increased it. Conversely, electrolytic lesion of the POA facilitated, while VMN lesion reduced antidromic spike invasion. 6. Thus, excitability of some neurons in the CG is facilitated by estrogen. Similar effects of VMN stimulation and POA lesion suggest that the estrogenic effect could be mediated by these structures. The pattern of effects on these CG neurons is that required for their control of lordosis behavior, an estrogen-dependent postural reflex in female rodents. These cells may modulate medullary reticulospinal cells, which in turn govern the reflex.

Saturating summation of the afterhyperpolarization conductance in spinal motoneurones: A mechanism for ‘secondary range’ repetitive firing

Summation of the potassium conductance (G K) changes underlying the spike afterhyperpolarization (AHP) has been studied in cat spinal motoneurones. Cells were directly activated by one to five short current pulses at constant rate, each evoking an action potential. The analysis was restricted to cells displaying an approximately exponential decay of the AHP conductance. In these neurones the AHP conductances given by successive spikes were found to summate in a non-linear manner. This non-linear summation seemed well described by a neurone model based on modified Hodgkin-Huxley equations. From the model equations the total AHP conductance in motoneurones could be calculated from values of G K measured experimentally at different times during the summation process. Adaptation and steady-state firing in motoneurones are assumed to be governed by summation of AHP conductance. The same model was then utilized for simulating neuronal repetitive firing in response to current steps. Such simulations were performed after substitution of the model parameters with values measured in individual motoneurones which had also been fired repetitively by intracellular injection of long-lasting current steps. The amount of adaptation and the shape and slopes of the steady-state frequency-to-current relation were found to coincide in the model and in the corresponding motoneurones.

Effect of repetitive activation on the afterhyperpolarization in dorsal spinocerebellar tract neurones.

1. The changes in the afterhyperpolarization (a.h.p.) with repetitive activation have been studied in dorsal spinocerebellar tract cells of the cat using intracellular recording techniques. 2. The a.h.p. following a single spike was conditioned at different interspike intervals by a single preceding spike. In the majority of neurones the a.h.p. following a spike added approximately linearly with that generated by a preceding spike. 3. In other cells the a.h.p. following a spike was instead depressed by a preceding spike. THis depression was approximately constant at interspike intervals less than the a.h.p. duration (50-100 msec). Thereafter the a.h.p. slowly recovered during the next 100-300 msec. There was no associated decrease in the initial brief hyperpolarizing undershoot. 4. With shortlasting repetitive activation at high frequency (greater than 100 impulses/sec) the a.h.p, peak amplitude increased progressively with successive spikes (5-15 spikes). No change in the time constant of decay was observed. A good correspondence was found between the observed increase in peak amplitude of the a.h.p.s and that given by a theoretical linear superposition of the successive a.h.p.s. 5. Changes in the brief hyperpolarizing undershoot with repetitive activation is also described.

Repetitive firing of Renshaw spinal interneurons.

A model of the Renshaw spinal interneuron has been developed. The model consists of a nonhomogeneous cylinder divided into three compartments: dendrites, soma and axon initial segment (I.S). The soma and dendrites are represented as a cylindrical cable by the method of Rall (1962); anatomical data of Jankowska and Lindstrom (1971) from fluorescent dye injections were used to construct the cable. The soma and I.S. membranes are assumed to have Hodgkin-Huxley-like membrane activity. In comparison with our previous model of a tonic motorneuron (Traub, 1977), the Renshaw cell has a faster membrane time constant, faster Hodgkin-Huxley rate functions, ? h and β h shifted to the right on the voltage axis, and no slow potassium conductance. With appropriate input conductances, the Renshaw cell model exhibits the following features: it develops very high frequency bursts (over 1000 impulses per s) which trail off over a period of 10---20 ms; the second spike has small amplitude and successive spikes develop progressively larger amplitudes. Comparisons are drawn with the experimental observations of Eccles et al. (1961) and Willis and Willis (`966). With this model, it is feasible to compute the steady firing rate for a large number of steady synaptic excitatory and inhibitory conductances by direct integration of the differential equations.

Depolarizing afterpotentials and burst production in molluscan pacemaker neurons.

1. Spikes in molluscan bursting cells are followed by depolarizing afterpotentials (DAPs) which are not seen in nonbursting cells in the same ganglia. DAPs from successive spikes sum to provide a depolarizing drive capable of sustaining multiple discharge. 2. Subthreshold depolarization activates a DAP-like process in bursters. 3. DAP amplitude increases as the cell is hyperpolarized beyond the potassium equilibrium potential. The amplitude is not changed by intracellular iontophoresis of TEA-Cl. DAP amplitude is reduced by 39% after a 10-min exposure to CA++-free saline, and by 66% after 10 min in 4% Na+ (Tris substituted) saline. The amplitude is unchanged by exposure to K+-free saline. 4. During repetitive stimulation the amplitude of the summed DAP declines. 5. It is concluded that DAP results from a slowly decaying component of Ca++ and Na+ permeability.

Characteristics of crayfish neuromuscular facilitation and their calcium dependence.

1. A quantitative description of facilitation in the crayfish claw opener muscle is presented. The facilitation of a test response following one or more conditioning stimuli, and the growth of facilitation during a tetanus, are measured.2. In superficial central fibres facilitation following one or more impulses can be described as the sum of two components which are both maximum at the end of the conditioning train and decline simultaneously and exponentially with different time constants thereafter.3. During a tetanus, facilitation to successive stimuli grows more rapidly than is predicted by assuming that each impulse adds a constant facilitative effect to an accumulating total state of facilitation.4. Sufficiently large values of tetanic facilitation are predicted by a model which assumes that transmitter release is proportional to the nth power of a substance or factor accumulating in nerve terminals. But no single value of n predicts the correct rise of facilitation in a tetanus and the time course of its subsequent decline from the facilitation following a single spike.5. A model which assumes that the facilitative effects of successive spikes multiply in a tetanus predicts responses that are larger than those observed.6. The effects of varying the calcium concentration ([Ca(2+)]) on transmitter release and facilitation were studied. When a magnesium-EDTA buffering system is used to vary [Ca(2+)], transmitter release is found to be nearly linearly related to [Ca(2+)] in the range 0.1-13.5 mM.7. The magnitude and time course of facilitation during and following a tetanus are unaffected by varying [Ca(2+)] between 1.0 and 40 mM.8. The relation between ;steady-state' facilitation and stimulus frequency is also unaffected by changing [Ca(2+)], except that in high [Ca(2+)] transmitter release appears to saturate at high frequencies (above 30 Hz).9. The results are discussed in terms of the ;calcium accumulation' hypothesis of facilitation. The findings in crayfish appear to be qualitatively consistent with this hypothesis if certain modifications are made in the hypothesis.

Patterned activity of the buccal ganglion of the nudibranch mollusc Archidoris pseudoargus.

Patterned activity of the buccal ganglion of the nudibranch mollusc Archidoris pseudoargus.

Computer dissection of peripheral nerve bundle activity

A program has been developed for the LINC8 (Digital Equipment Corporation) computer for sorting neuronal activity recorded grossly from nerve bundles into the component activity of the individual nerve fibers. Activity was recorded at two points along the nerve bundle, a technique which provided conduction velocity information for the individual nerve fibers. The most successful spike separations were possible when the shape of spikes recorded at the most distal recording site were employed, along with conduction velocity information.

Electrophysiological actions of oxytocin on the rabbit myometrium.

The electrical activities of myometrial cells of the pregnant rabbit uterus have been studied by means of sucrose-gap and intracellular micro-electrode recording techniques. The resting potential of the myometrial cell was about -50 mv, and it is unaffected by the duration of pregnancy or placental attachment. Action potentials of the myometrium, although dependent on external Na(+), were not always of the regenerative type; preparations from nonparturient uteri often produce mainly small spikes. The mean spike amplitude was 35 mv, rising at a mean maximum rate of 3 v/sec. Oxytocin, in concentrations less than 500 microU/ml, increased the mean spike amplitude to 48 mv and the mean maximum rate of rise to 7 v/sec, without affecting the resting potential. The relation between membrane potential and dV/dt of the spike was steepened by oxytocin, suggesting that oxytocin increased the number of normally sparse sodium gates in the myometrial membrane. By this action, oxytocin is believed to increase the probability of successful regenerative spikes and thereby initiate electrical activity in quiescent preparations, increase the frequency of burst discharges, the number of spikes in each burst, and the amplitude of spikes in individual cells.