The functional consequences of paraoxon exposure in central neurones of land snail, Caucasotachea atrolabiata, are partly mediated through modulation of Ca2+ and Ca2+-activated K+-channels

Toxicity of paraoxon has been attributed to inhibition of cholinesterase, but little is known about its direct action on ionic channels. The effects of paraoxon (0.3 microM-0.6 microM) were studied on the firing behaviour of snail neurones. Paraoxon significantly increased the frequency of spontaneously generated action potentials, shortened the afterhyperpolarization (AHP) and decreased the precision of firing. Short periods of high frequency-evoked trains of action potentials led to an accumulation in the depth and duration of post-train AHPs that was evidenced as an increase in time to resumption of autonomous activity. The delay time in autonomous activity initiation was linearly related to the frequency of spikes in the preceding train and the slope of the curve significantly decreased by paraoxon. The paraoxon induced hyperexcitability and its depressant effect on the AHP and the post-train AHP were not blocked by atropine and hexamethonium. Calcium spikes were elicited in a Na+ free Ringer containing voltage dependent potassium channel blockers. Paraoxon significantly decreased the duration of calcium spikes and following AHP and increased the frequency of spikes. These findings suggest that a reduction in calcium influx during action potential may decrease the activation of calcium dependent potassium channels that participate in AHP generation and act as a mechanism of paraoxon induced hyperexcitability.     

Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells

Cortical pyramidal cells fire single spikes and complex spike bursts. However, neither the conditions necessary for triggering complex spikes, nor their computational function are well understood. CA1 pyramidal cell burst activity was examined in behaving rats. The fraction of bursts was not reliably higher in place field centers, but rather in places where discharge frequency was 6-7 Hz. Burst probability was lower and bursts were shorter after recent spiking activity than after prolonged periods of silence (100 ms-1 s). Burst initiation probability and burst length were correlated with extracellular spike amplitude and with intracellular action potential rising slope. We suggest that bursts may function as "conditional synchrony detectors," signaling strong afferent synchrony after neuronal silence, and that single spikes triggered by a weak input may suppress bursts evoked by a subsequent strong input.     

Electrical properties of the dendrite in an insect mechanoreceptor: Effects of antidromic or direct electrical stimulation

A study of the negative phase of the spikes recorded extra cellularly from insect mechanoreceptor has been performed in order to characterize some electrical properties of the dendrite which contains the transducing part of the sensory neuron. These properties have been investigated in mechanoreceptors of the metathoracic leg of the locust Schistocerca gregaria by firing antidromic action potentials both at rest and during mechanical or electrical stimulation. The amplitude of the negative phase of the spike appears to be correlated with the polarization of the dendritic membrane, although when bursts of action potentials are applied, the relation is more complex, including a depressive influence of a given spike on the following spike. The receptor potential and the antidromic dendritic spikes both originate in the same region of the dendrite but they involve different ionic processes. Our results indicate that the dendrite is electrically excitable. The spike which originates in the dendrite has an initial negative phase with a small superimposed positive component. A spike of this shape is never observed under natural stimulation. It is proposed that the negative phase of the antidromic impulse provides a suitable means for studying the variations in electrical polarization of the dendrite which cannot be recorded directly.     

Ca2+-dependent depolarization and burst firing of rat CA1 pyramidal neurones induced by N-methyl-D-aspartic acid and quinolinic acid: antagonism by 2-amino-5-phosphonovaleric and kynurenic acids

The excitatory effects of microiontophoretically applied quisqualic (QUIS), N-methyl-D-aspartic (NMDA), and quinolinic (QUIN) acids were investigated using intracellular recording from CAl pyramidal neurones in slices of rat hippocampus. QUIS evoked only simple action potentials superimposed upon a depolarization which attained a clear plateau. When this level had been reached, increased ejecting currents did not produce further depolarization. By contrast, with low currents NMDA and QUIN elicited small membrane depolarizations which triggered bursts of action potentials superimposed upon rhythmically occurring depolarizing shifts. Larger currents caused depolarization which if sufficiently large completely blocked spike activity. Tetrodotoxin (TTX) prevented the spikes evoked by QUIS and the bursts of action potentials seen with NMDA and QUIN, and the rhythmic depolarizing shifts then appeared as broad spikes of up to 50 mV in amplitude. These and the underlying membrane depolarization were blocked by Co2+, by the NMDA antagonist D(-)-2-amino-5-phosphonovaleric acid (DAPV), and by kynurenic acid (KYNU). It thus appears that the depolarization and burst firing of rat CAl pyramidal neurones elicited by NMDA and QUIN are Ca2+ dependent while the actions of QUIS are not.     

Coding with spike shapes and graded potentials in cortical networks

In cortical neurones, analogue dendritic potentials are thought to be encoded into patterns of digital spikes. According to this view, neuronal codes and computations are based on the temporal patterns of spikes: spike times, bursts or spike rates. Recently, we proposed an 'action potential waveform code' for cortical pyramidal neurones in which the spike shape carries information. Broader somatic action potentials are reliably produced in response to higher conductance input, allowing for four times more information transfer than spike times alone. This information is preserved during synaptic integration in a single neurone, as back-propagating action potentials of diverse shapes differentially shunt incoming postsynaptic potentials and so participate in the next round of spike generation. An open question has been whether the information in action potential waveforms can also survive axonal conduction and directly influence synaptic transmission to neighbouring neurones. Several new findings have now brought new light to this subject, showing cortical information processing that transcends the classical models.     

Bursts and isolated spikes code for opposite movement directions in midbrain electrosensory neurons

Directional selectivity, in which neurons respond strongly to an object moving in a given direction but weakly or not at all to the same object moving in the opposite direction, is a crucial computation that is thought to provide a neural correlate of motion perception. However, directional selectivity has been traditionally quantified by using the full spike train, which does not take into account particular action potential patterns. We investigated how different action potential patterns, namely bursts (i.e. packets of action potentials followed by quiescence) and isolated spikes, contribute to movement direction coding in a mathematical model of midbrain electrosensory neurons. We found that bursts and isolated spikes could be selectively elicited when the same object moved in opposite directions. In particular, it was possible to find parameter values for which our model neuron did not display directional selectivity when the full spike train was considered but displayed strong directional selectivity when bursts or isolated spikes were instead considered. Further analysis of our model revealed that an intrinsic burst mechanism based on subthreshold T-type calcium channels was not required to observe parameter regimes for which bursts and isolated spikes code for opposite movement directions. However, this burst mechanism enhanced the range of parameter values for which such regimes were observed. Experimental recordings from midbrain neurons confirmed our modeling prediction that bursts and isolated spikes can indeed code for opposite movement directions. Finally, we quantified the performance of a plausible neural circuit and found that it could respond more or less selectively to isolated spikes for a wide range of parameter values when compared with an interspike interval threshold. Our results thus show for the first time that different action potential patterns can differentially encode movement and that traditional measures of directional selectivity need to be revised in such cases.     

Ephaptic coupling in white matter fibre bundles modulates axonal transmission delays

Axonal connections are widely regarded as faithful transmitters of neuronal signals with fixed delays. The reasoning behind this is that extracellular potentials caused by spikes travelling along axons are too small to have an effect on other axons. Here we devise a computational framework that allows us to study the effect of extracellular potentials generated by spike volleys in axonal fibre bundles on axonal transmission delays. We demonstrate that, although the extracellular potentials generated by single spikes are of the order of microvolts, the collective extracellular potential generated by spike volleys can reach several millivolts. As a consequence, the resulting depolarisation of the axonal membranes increases the velocity of spikes, and therefore reduces axonal delays between brain areas. Driving a neural mass model with such spike volleys, we further demonstrate that only ephaptic coupling can explain the reduction of stimulus latencies with increased stimulus intensities, as observed in many psychological experiments.     

Complex evolution of spike patterns during burst propagation through feed-forward networks

Stable signal transmission is crucial for information processing by the brain. Synfire-chains, defined as feed-forward networks of spiking neurons, are a well-studied class of circuit structure that can propagate a packet of single spikes while maintaining a fixed packet profile. Here, we studied the stable propagation of spike bursts, rather than single spike activities, in a feed-forward network of a general class of excitable bursting neurons. In contrast to single spikes, bursts can propagate stably without converging to any fixed profiles. Spike timings of bursts continue to change cyclically or irregularly during propagation depending on intrinsic properties of the neurons and the coupling strength of the network. To find the conditions under which bursts lose fixed profiles, we propose an analysis based on timing shifts of burst spikes similar to the phase response analysis of limit-cycle oscillators.     

Current recording from sensory cilia of olfactory receptor cells in situ. I. The neuronal response to cyclic nucleotides

The olfactory mucosa of the frog was isolated, folded (the outer, ciliated side faced outward), and separately superfused with Ringers solution on each side. A small number of sensory cilia (one to three) were pulled into the orifice of a patch pipette and current was recorded from them. Fast bipolar current transients, indicating the generation of action potentials by the receptor cells, were transmitted to the pipette, mainly through the ciliary capacitance. Basal activity was near 1.5 spikes s-1. Exposure of apical membrane areas outside of the pipette to permeant analogues of cyclic nucleotides, to forskolin, and to phosphodiesterase inhibitors resulted in a dose-dependent acceleration of spike rate of all cells investigated. Values of 10-20 s-1 were reached. These findings lend further support to the notion that cyclic nucleotides act as second messengers, which cause graded membrane depolarization and thereby a graded increase in spike rate. The stationary spike rate induced by forskolin was very regular, while phosphodiesterase inhibitors caused (in the same cell) an irregular pattern of bursts of spikes. The response of spike rate was phasic-tonic in the case of strong stimulation, even when elicited by inhibitors of phosphodiesterase or by analogues of cyclic nucleotides that are not broken down by the enzyme. Thus, one of the mechanisms contributing to desensitization appears to operate at the level of the nucleotide-induced ciliary conductance. However, desensitization at this level was slow and only partial, in contrast to results obtained with isolated, voltage-clamped receptor cells.     

Electrophysiology of "yellow cells," neurosecretory neurones in Lymnaea.

The thirty Yellow Cells of Lymnaea show single, double and other extra spike modes of firing. Yellow Cell bursts consist of various combinations of single, doublet and triplet spikes whose number per burst varies spontaneously. Single spike firing modes of activity can be converted into doublets or bursts (and vice versa) by applying steady currents of the appropriate polarity. Spike activity is basically endogenous although it is modulated by low frequency synaptic input originating from within the brain. Interburst interval is affected by the number of spikes occurring in the preceding burst. This varies spontaneously or can be induced by applying appropriately timed current pulses or occurs following synaptic input. Excitatory synaptic input often induces bursts which far exceed the duration of the input and which are followed by long periods of inhibition.     

Afterhyperpolarization improves spike programming through lowering threshold potentials and refractory periods mediated by voltage-gated sodium channels

Neurons program various patterns of sequential spikes as neural codes to guide animal behavior. Studies show that spike programming (capacity and timing precision) is influenced by inhibitory synaptic inputs and membrane afterhyperpolarization (AHP). Less is clear about how these inhibitory components regulate spike programming, which we investigated at the cortical neurons. Whole-cell current-clamp recording for action potentials and single channel recording for voltage-gated sodium channels (VGSC) were conducted at regular-spiking and fast-spiking neurons in the cortical slices. With quantifying the threshold potentials and refractory periods of sequential spikes, we found that fast-spiking neurons expressing AHP possess lower threshold potentials and shorter refractory periods, and the hyperpolarization pulse immediately after each of spikes lowers threshold potentials and shortens refractory periods at regular-spiking neurons. Moreover, the hyperpolarization pulses shorten the refractory periods for VGSC reactivation and threshold potentials for its sequential activation. Our data indicate that inhibitory components immediately after spikes, such as AHP and recurrent inhibition, improve spike capacity and timing precision via lowering the refractory periods and threshold potentials mediated by voltage-gated sodium channels.     

Efficient inhibition of bursts by bursts in the auditory system of crickets

In crickets, auditory information about ultrasound is carried bilaterally to the brain by the AN2 neurons. The ON1 neuron provides contralateral inhibitory input to AN2, thereby enhancing bilateral contrast between the left and right AN2s, an important cue for sound localization. We examine how the structures of the spike trains of these neurons affect this inhibitory interaction. As previously shown for AN2, ON1 responds to salient peaks in stimulus amplitude with bursts of spikes. Spike bursts, but not isolated spikes, reliably signal the occurrence of specific features of the stimulus. ON1 and AN2 burst at similar times relative to the amplitude envelope of the stimulus, and bursts are more tightly time-locked to stimulus feature than the isolated spikes. As a consequence, spikes that, in the absence of contralateral inhibition, would occur within AN2 bursts are more likely to be preceded by spikes in ON1 (mainly also in bursts) than are isolated AN2 spikes. This leads to a large decrease in the burst rate of the inhibited AN2. We conclude that the match in coding properties of ON1 and AN2 allows contralateral inhibition to be most efficient for those portions of the response that carry the behaviourally relevant information, i.e. for bursts. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Electrical properties of neurons recorded from the rat supraoptic nucleus in vitro

The electrical properties of neurons in the supraoptic nucleus (so.n.) have been studied in the hypothalamic slice preparation by intracellular and extracellular recording techniques, with Lucifer Yellow CH dye injection to mark the recording site as being the so.n. Intracellular recordings from so.n. neurons revealed them to have an average membrane potential of -67 +/- 0.8 mV (mean +/- s.e.m.), membrane resistance of 145 +/- 9 M omega with linear current-voltage relations from 40 mV in the hyperpolarizing direction to the level of spike threshold in the depolarizing direction. Average cell time constant was 14 +/- 2.2 ms. So.n. action potentials ranged in amplitude from 55 to 95 mV, with a mean of 76 +/- 2 mV, and a spike width of 2.6 +/- 0.5 ms at 30% of maximal spike height. Both single spikes and trains of spikes were followed by a strong, long-lasting hyperpolarization with a decay fitted by a single exponential having a time constant of 8.6 +/- 1.8 ms. Action potentials could be blocked by 10(-6) M tetrodotoxin. Spontaneously active so.n. neurons were characterized by synaptic input in the form of excitatory and inhibitory postsynaptic potentials, the latter being apparently blocked when 4 M KCl electrodes were used. Both forms of synaptic activity were blocked by application of divalent cations such as Mg2+, Mn2+ or Co2+. 74% of so.n. neurons fired spontaneously at rates exceeding 0.1 spikes per second, with a mean for all cells of 2.9 +/- 0.2 s-1. Of these cells, 21% fired slowly and continuously at 0.1 - 1.0 s-1, 45% fired continuously at greater than 1 Hz, and the remaining 34% fired phasically in bursts of activity followed by silence or low frequency firing. Spontaneously firing phasic cells showed a mean burst length of 16.7 +/- 4.5 s and a silent period of 28.2 +/- 4.2 s. Intracellular recordings revealed the presence of slow variations in membrane potential which modified the neuron's proximity to spike threshold, and controlled phasic firing. Variations in synaptic input were not observed to influence firing in phasic cells.     

Critical parameters of the spike trains in a cell assembly: coding of turn direction by the giant interneurons of the cockroach

Cockroaches (Periplaneta americana) respond to air displacement produced by an approaching predator by turning and running away. A set of 4 bilateral pairs of ventral giant interneurons is important in determining turn direction. Wind from a given side is known to produce more spikes, an earlier onset of the spike trains, and different fine temporal patterning, in the ipsilateral vs the contralateral set of these interneurons. Here we investigate which of these spike train parameters the cockroach actually uses to determine the direction it will turn.We delivered controlled wind puffs from the right front, together with intracellular injection of spike trains in a left ventral giant interneuron, under conditions where the animal could make normally directed turning movements of the legs and body. In trials where our stimuli caused the left side to give both the first spike and more total spikes than the right, but where our injected spike train included none of the normal fine temporal patterning, 92% of the evoked turns were to the rightopposite of normal (Figs. 4–6). In trials where the left side gave the first spike, but the right side gave more spikes, 100% of the turns were to the left-the normal direction (Figs. 8, 9). Comparable results were obtained when each of the left giant interneurons 1, 2 or 3 were electrically stimulated, and when either weak or stronger wind puffs were used. Stimulating a left giant interneuron electrically in the absence of a wind puff evoked an escape-like turn on 9% of the trials, and these were all to the right (Fig. 9).These results indicate that fine temporal patterning in the spike trains is not necessary, and information about which side gives the first spike is not sufficient, to determine turn direction. Rather, the key parameter appears to be relative numbers of action potentials in the left vs the right group of cells. These conclusions were supported by similar experiments in which extracellular stimulation of several left giant interneurons was paired with right wind (Figs. 11, 12).Abbreviations GI giant interneuron - vGI ventral giant interneuron - dGI dorsal giant interneuron - LY Lucifer yellow - CF carboxyfluorescein     

Neurophysiology of Ganglia of Auerbach's Plexus

The enteric plexuses of the automatic nervous system may beconsidered, on the basis of both function and morphology, tobe a simple integrative nervous system of vertebrate animals.Microelectrcde studies of single unit activity within entericganglia reveal four distinct types of ganglion cells distinguishedon the basis of pattern of spike discharge. These are (i) burst-typeunits which spontaneously discharge bursts of spikes at periodicintervals; (ii) fast- and slowly-adapting mechanoreceptors;(iii) tonic-type units which respond to mechanical stimulationwith prolonged, all-or-nothing trains of spikes; (iv) single-spikeunits which spontaneously discharge single action potentialsat variable intervals. The enteric plexuses are adapted forcontrol of the intestinal musculature which behaves as an electricalsyncytium activated by myogenic pacemaker potentials. The mechanismof neural control is integration of continuous neurogenic inhibitionof the inherently excitable musculature.     

Direction of action potential propagation influences calcium increases in distal dendrites of the cricket giant interneurons

To understand the relationship between the propagation direction of action potentials and dendritic Ca(2+) elevation, simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and intradendritic membrane potential were performed in the wind-sensitive giant interneurons of the cricket. The dendritic Ca(2+) transients induced by synaptically-evoked action potentials had larger amplitudes than those induced by backpropagating spikes evoked by antidromic stimulation. The amplitude of the [Ca(2+)](i) changes induced by antidromic stimuli combined with subthreshold synaptic stimulation was not different from that of the Ca(2+) increases evoked by the backpropagating spikes alone. This result means that the synaptically activated Ca(2+) release from intracellular stores does not contribute to enhancement of Ca(2+) elevation induced by backpropagating spikes. On the other hand, the synaptically evoked action potentials were also increased at distal dendrites in which the Ca(2+) elevation was enhanced. When the dendritic and axonal spikes were simultaneously recorded, the delay between dendritic spike and ascending axonal spike depended upon which side of the cercal nerves was stimulated. Further, dual intracellular recording at different dendritic branches illustrated that the dendritic spike at the branch arborizing on the stimulated side preceded the spike recorded at the other side of the dendrite. These results suggest that the spike-initiation site shifts depending on the location of the activated postsynaptic site. It is proposed that the difference of spike propagation manner could change the action potential waveform at the distal dendrite, and could produce synaptic activity-dependent Ca(2+) dynamics in the giant interneurons.     

Vernalization,a Switch in Initiation of Flowering,Promotes Differentiation and Development of Spikelet in Winter Wheat

Vernalization is a decisive physiological process for heading, flowering and graining of biennial plants. Variable duration of low-temperature treatment has effects on lateral morphogenesis, such as spike initiation, floral development and graining rate in winter wheat ( Triticum aestivum L.). The investigation data showed that the duration of vernalization treatment was a decisive factor for the initiation of spike relevant to the time of initiation; the longer the duration at low temperature, the earlier the spike initiation in winter wheat. In the process of the spike differentiation, relatively lower temperature and longer differential time benefited for spike differentiation. Under laboratory condition, a low-temperature treatment for 45 d was optial for flower differentiation and graining in winter wheat. It is novelly recognized that vernalization treatment is essential for development of both spikes and spikelets, besides for promoting initiation of differentiation in winter wheat.     

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.     

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 µU/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.