Electrophysiological evidence for tetrodotoxin-resistant sodium channels in slowly conducting dural sensory fibers

A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small diameter neurons of peripheral sensory ganglia. The peripheral axons of sensory neurons appear to lack this channel, but its presence has not been investigated in peripheral nerve endings, the site of sensory transduction in vivo. We investigated the effect of TTX on mechanoresponsiveness in nerve endings of sensory neurons that innervate the intracranial dura. Because the degree of TTX resistance of axonal branches could potentially be affected by factors other than channel subtype, the neurons were also tested for sensitivity to lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium channels. Single-unit activity was recorded from dural afferent neurons in the trigeminal ganglion of urethan-anesthetized rats. Response thresholds to mechanical stimulation of the dura were determined with von Frey monofilaments while exposing the dura to progressively increasing concentrations of TTX or lidocaine. Neurons with slowly conducting axons were relatively resistant to TTX. Application of 1 microM TTX produced complete suppression of mechanoresponsiveness in all (11/11) fast A-delta units [conduction velocity (c.v.) 5-18 m/s] but only 50% (5/10) of slow A-delta units (1.5 相似文献   

The role of cGMP in the extinction of the reactions of identified neurons of the edible snail in response to acetylcholine

The possible role of cGMP in the regulation of the extinction of the reactions of the RPa4, RPa3, and LPa3 neurons of the edible snail in response to acetylcholine (ACh), applied rhythmically to the soma of the neuron by means of microiontophoresis, has been investigated. It was demonstrated that activators of guanylate cyclase which increased the level of cGMP in the cell, namely, sodium nitroprusside and sodium azide (5·10⁴ 10³ mole/liter), when applied intracellularly, intensify the extinction of inward transmembrane current and of depolarization of the membrane in response to ACh. The hypothesis of the participation of cGMP-dependent phosphorylation of membrane proteins in the regulation of the rate of development, depth, and duration of short-lived plasticity of the cholinoreceptors of the neuron is proposed.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 39, No. 4, pp. 728–736, July–August, 1989.     

Analysis of passive and active electrophysiologic properties of neurons in mammalian nodose ganglia maintained in vitro.

1. We studied the passive and active electrical properties of the soma membrane of neurons in nodose ganglia removed from cats and rabbits and maintained in vitro. The ganglia were superfused at 37 degrees C with a solution formulated to approximate the extracellular fluid of each species. The solution was buffered to pH 7.34, continuously equilibrated with 95% O2 and 5% CO2, and contained dialyzed calf serum and glucose. We also examined these properties in nodose ganglion neurons in vivo. Intracellular recordings were obtained with glass micropipettes filled with either 3 M KCl or 5 M K acetate. 2. We determined mean values for a variety of passive and active electrophysiologic properties. Values obtained in vitro did not differ significantly from those obtained in vivo. Based on the passive electrical properties of the soma membrane, neurons in the nodose ganglion appear to be a uniform population, despite the different sensory modalities conveyed by the afferent fibers. 3. Cell bodies of neurons generated action potentials in response to impulses in their afferent fibers. Somatic spikes could be evoked by stimulation of either the supranodose or infranodose vagus nerve, and an inflection point could be seen on their rising phase. When the vagus nerve was stimulated at frequencies greater than 10-20 Hz, the generation of somatic spikes often became progressively delayed and then failed completely, leaving a smaller potential (IS spike) which was apparently generated in the initial complex. The afterhyperpolarization was associated only with the somatic spike. 4. Many neurons, both in vitro and in vivo, developed a persistent hyperpolarization when repetitive action potentials occurred in the soma. This hyperpolarization was apparent at frequencies as low as 1-2 Hz, persisted for up to 5 s after the occurrence of the last somatic spike, and sometimes caused failure of somatic spikes to be generated. 5. Neurons in both species differed in their responses to suprathreshold depolarization applied through the recording electrode. Some neurons produced a train of action potentials which lasted for the duration of the depolarizing pulse, the frequency of the train being related to the magnitude of depolarization. The trains were characterized by gradually decreasing spike amplitudes and increasing interspike intervals. Other neurons responded with only a single spike or brief burst of action potentials at the beginning of depolarization to threshold. 6. It is suggested that the adaptive properties of the soma membrane of a peripheral sensory neuron are similar to those of its sensory ending, and that electrophysiological studies of the soma membrane may provide an opportunity to examine mechanisms of receptor adaptation.     

Effects of hypothalamic stimulation on activity of dorsomedial medulla neurons that respond to subdiaphragmatic vagal stimulation

1. Effects of hypothalamic stimulation on activity of dorsomedial medulla neurons that responded to subdiaphragmatic vagal stimulation were investigated in urethan-anesthetized rats. 2. Extracellular recordings were made from 231 neurons in the nucleus of the tractus solitarius (NTS) that fired repetitively in response to single-pulse subdiaphragmatic vagal stimulation and from 320 neurons in the dorsal motor nucleus of the vagal nerve (DMV) that responded antidromically to subdiaphragmatic vagal stimulation. The mean latencies of responses to subdiaphragmatic vagal stimulation were 90.3 +/- 17.1 ms (mean +/- SD) for NTS neurons, and 90.8 +/- 11.2 ms for DMV neurons. This indicated that both afferent and efferent subdiaphragmatic vagal fibers were thin and unmyelinated and had a conduction velocity of approximately 1 m/s. 3. In extracellular recordings from 320 DMV neurons, marked inhibition preceded the antidromic response and subdiaphragmatic vagal stimulation evoked orthodromic spikes in only a few neurons. 4. Intracellular recordings from 66 DMV neurons revealed inhibitory postsynaptic potentials (IPSPs) before the antidromic responses. These IPSPs suppressed spontaneous firing and prevented excitatory postsynaptic potentials (EPSPs) from generating action potentials. 5. Stimulation in all hypothalamic loci studied, the ventromedial hypothalamic nucleus (VMH), the lateral hypothalamic area (LHA), and the paraventricular nucleus (PVN), induced responses with similar characteristics of excitation alone or excitation followed by inhibition in most NTS and DMV neurons. 6. No reciprocal effect of VMH and LHA stimulation was observed on NTS and DMV neurons. 7. Intracellular recordings from DMV neurons revealed monosynaptic EPSPs in response to stimulation of the VMH, the LHA, and the PVN. 8. PVN stimulation evoked significantly more responses in NTS and DMV neurons than VMH stimulation and more responses in DMV neurons than LHA stimulation. This suggests a difference in the number of connections between each hypothalamic site and the dorsomedial medulla. 9. The same dorsomedial medulla neurons were tested with VMH and LHA stimulation. The respective mean latencies of the antidromic and the orthodromic NTS neuron responses were 37.3 +/- 3.2 and 39.6 +/- 12.9 ms for VMH stimulation and 29.8 +/- 5.3 and 31.8 +/- 8.7 ms for LHA stimulation. The mean latencies of the orthodromic DMV neuron responses were 39.4 +/- 8.3 ms for VMH stimulation and 31.1 +/- 5.2 ms for LHA stimulation. The estimated conduction velocity from the VMH to the dorsomedial medulla was approximately 0.25 m/s and from the LHA it was approximately 0.33 m/s, which was significantly faster.(ABSTRACT TRUNCATED AT 400 WORDS)     

海马CA1锥体神经元放电波形的数值研究

本文应用神经元房室模型,构造了一个由31个房室组成的海马CAI锥体神经元房室模型,用数值方法探讨海马CAI锥体神经元的放电波形特点。以持续钠电导、快速钠电导和胞体树突耦合强度为例,研究它们对放电波形的影响。结果：①放电波形对持续钠电导非常敏感,持续钠电导的微小改变也能导致放电波形的明显变化;②放电波形每个Burst中Spike个数与快速钠电导存在着明显的线性递增关系;③随着胞体树突耦合强度的增加,每个Burst中Spike个数在急剧减少。     

Fast and slow pyramidal tract neurons: an intracellular analysis of their contrasting repetitive firing properties in the cat.

1. Intracellular recordings were made from an estimated 500 neurons in the sensorimotor cortex of barbiturate-anesthetized cats. Of those which were antidromically identified from the medullary pyramids, 70 were selected which also exhibited steady repetitive firing to steps of current injected through the recording electrode; 81% were "fast" (conduction velocity greater than 20 m/s) and 19% were "slow". 2. As shown by earlier workers, the spike duration is a function of conduction velocity; a spike duration of 1.0 ms is the dividing line between fast and slow. 3. Of the 57 fast pyramidal tract neurons (PTNS), 14 exhibited double spikes during otherwise rhythmic firing patterns to a step of injected current. These very short interspike intervals (usually 1.5-2.5 ms) were first seen interspersed in a rhythmic discharge (e.g., 50-ms intervals) but, with further increases in current strength, would come to dominate the firing pattern; e.g., double spikes every 40 ms. Further increases in current would typically shorten only the long intervals; e.g., 40-30 ms, but some fast PTNS developed triple spikes, etc. 4. The extra spike appears to arise from a large hump which follows most spikes in fast PTNS; while this humplike "depolarising after-potential" can also be seen in slow PTNS, it is small. Extra spikes were seen only in fast PTNS with large postspike humps; in perhaps half of the fast PTNS, extra spikes probably contributed to "adaptation." 5. Slow PTNS often had frequency-current curves which were not repeatable; a "hysteresis" phenomenon could often be seen, where the proportionality constant relating current to firing rate decreased following high firing rates. 6.The B spike was distinguishable from the A spike in differentiated antidromic spikes in 77% of the slow PTNS, in only 14% of the fast PTNS which later exhibited double spikes during current-induced repetitive firing, and in 53% of the other fast PTNS. 7. The antidromic spike heights of doublet PTNS were not significantly different from those of other repetitively firing PTNS.     

Intracellular study of oculomotor neurons in the rat

The electrical and morphological properties of oculomotor neurons were investigated in the rat with intracellular recordings and intracellular horseradish peroxidase staining. Motoneurons were identified by their antidromic response to electrical stimulation of the ipsilateral medial rectus muscle.

The antidromic action potential was followed by a delayed depolarization and an afterhyperpolarization of 20–50 ms in duration. The whole neuron input resistance calculated from intensity/voltage curves, was found between 4 and 15 MΩ. Passive membrane properties showed the existence of anomalous rectifications. Motoneurons were studied on the basis of their responses to long-lasting depolarizing current pulses. The intensity/frequency curves suggest the existence of two ranges of discharges. The average intensity frequency slope during the steady state was 33 imp/s/nA. Ten oculomotor neurons were intracellularly labelled with horseradish peroxidase and fully reconstructed. The soma (23–33 μm in diameter) gave off five-eight primary dendrites which could extend over 600–800 μm from the soma. The oculomotor neurons were principally oriented in the sagittal plane. The soma size of oculomotor neurons was not related to the size of proximal tree. According to our observations, the morphological features of motoneurons did not allow us to predict the whole neuron input resistance.

The comparison between in vivo and in vitro studies of oculomotor neurons revealed one major difference in the input resistance of the whole neuron which was three times higher in slices.     

Conditions for the triggering of spreading depression studied with computer simulations

In spite of five decades of study, the biophysics of spreading depression (SD) is incompletely understood. Earlier we have modeled seizures and SD, and we have shown that currents through ion channels normally present in neuron membranes can generate SD-like depolarization. In the present study, we define the conditions for triggering SD and the parameters that influence its course in a model of a hippocampal pyramidal cell with more complete representation of ions and channels than the previous version. "Leak" conductances for Na(+), K(+), and Cl(-) and an ion pump were present in the membrane of the entire cell; fast inactivating voltage dependent conductances for sodium and potassium in the soma; "persistent" conductances in soma and apical dendrite, and K(+)- and voltage-dependent N-methyl-D-aspartate (NMDA)-controlled conductance in the apical dendrite. The neuron was surrounded by restricted interstitial space and by a "glia-endothelium" system of extracellular ion regulation bounded by a membrane having leak conductances and an ion pump. Ion fluxes and concentration changes were continuously computed as well as osmotic cell volume changes. As long as reuptake into the neuron and "buffering" by glia kept pace with K(+) released from the neuron, stimulating current applied to the soma evoked repetitive firing that stopped when stimulation ceased. When glial uptake was reduced, K(+) released from neurons could accumulate in the interstitium and keep the neuron depolarized so that strong depolarizing pulses injected into the soma were followed either by afterdischarge or SD. SD-like depolarization was ignited when depolarization spreading into the apical dendrite, activated persistent Na(+) current and NMDA-controlled current. With membrane parameters constant, varying the injected stimulating current influenced SD onset but neither the depolarization nor the increase in extracellular K(+). Glial "leak" conductance influenced SD duration and SD ignition point. Varying maximal conductances (representing channel density) also influenced SD onset time but not the amplitude of the depolarization. Hypoxia was simulated by turning off the Na-K exchange pump, and this resulted in SD-like depolarization. The results confirm that, once ignited, SD runs an all-or-none trajectory, the level of depolarization is governed by feedback involving ion shifts and glutamate acting on ion channels and not by the number of channels open, and SD is ignited if the net persistent membrane current in the apical dendrites turns inward.     

Passive soma facilitates submillisecond coincidence detection in the owl's auditory system

Neurons of the avian nucleus laminaris (NL) compute the interaural time difference (ITD) by detecting coincident arrivals of binaural signals with submillisecond accuracy. The cellular mechanisms for this temporal precision have long been studied theoretically and experimentally. The myelinated axon initial segment in the owl's NL neuron and small somatic spikes observed in auditory coincidence detector neurons of various animals suggest that spikes in the NL neuron are generated at the first node of Ranvier and that the soma passively receives back-propagating spikes. To investigate the significance of the "passive soma" structure, we constructed a two-compartment NL neuron model, consisting of a cell body and a first node, and systematically changed the excitability of each compartment. Here, we show that a neuron with a less active soma achieves higher ITD sensitivity and higher noise tolerance with lower energy costs. We also investigate the biophysical mechanism of the computational advantage of the "passive soma" structure by performing sub- and suprathreshold analyses. Setting a spike initiation site with high sodium conductance, not in the large soma but in the small node, serves to amplify high-frequency input signals and to reduce the impact and the energy cost of spike generation. Our results indicate that the owl's NL neuron uses a "passive soma" design for computational and metabolic reasons.     

Effects of odor stimulation on antidromic spikes in olfactory sensory neurons

Spikes were evoked in rat olfactory sensory neuron (OSN) populations by electrical stimulation of the olfactory bulb nerve layer in pentobarbital anesthetized rats. The latencies and recording positions for these compound spikes showed that they originated in olfactory epithelium. Dual simultaneous recordings indicated conduction velocities in the C-fiber range, around 0.5 m/s. These spikes are concluded to arise from antidromically activated olfactory sensory neurons. Electrical stimulation at 5 Hz was used to track changes in the size and latency of the antidromic compound population spike during the odor response. Strong odorant stimuli suppressed the spike size and prolonged its latency. The latency was prolonged throughout long odor stimuli, indicating continued activation of olfactory receptor neuron axons. The amounts of spike suppression and latency change were strongly correlated with the electroolfactogram (EOG) peak size evoked at the same site across odorants and across stimulus intensities. We conclude that the curve of antidromic spike suppression gives a reasonable representation of spiking activity in olfactory sensory neurons driven by odorants and that the correlation of peak spike suppression with the peak EOG shows the accuracy of the EOG as an estimate of intracellular potential in the population of olfactory sensory neurons. In addition, these results have important implications about traffic in olfactory nerve bundles. We did not observe multiple peaks corresponding to stimulated and unstimulated receptor neurons. This suggests synchronization of spikes in olfactory nerve, perhaps by ephaptic interactions. The long-lasting effect on spike latency shows that action potentials continue in the nerve throughout the duration of an odor stimulus in spite of many reports of depolarization block in olfactory receptor neuron cell bodies. Finally, strong odor stimulation caused almost complete block of antidromic spikes. This indicates that a very large proportion of olfactory axons was activated by single strong odor stimuli.     

Responses of medullary raphespinal neurons to electrical stimulation of thoracic sympathetic afferents, vagal afferents, and to other sensory inputs in cats.

1. Medullary raphespinal neurons antidromically activated from the T2-T5 segments were tested for responses to electrical stimulation of cervical vagal and thoracic sympathetic afferents (by stimulating the left stellate ganglion), somatic probing, auditory stimuli, and visual stimuli in cats anesthetized with alpha-chloralose. A total of 99 neurons in the raphe nuclei were studied; the locations of 76 cells were histologically confirmed. Neurons were located in raphe magnus (RM, 65%), raphe obscurus (RO, 32%), and raphe pallidus (RPa, 4%). The mean conduction velocity of these neurons was 62 +/- 2.9 (SE) m/s with a range of 1.1-121 m/s. 2. A total of 60/99 tested neurons responded to electrical stimulation of sympathetic afferents. Quantitation of responses was obtained for 55 neurons. With one exception, all responsive neurons were excited and exhibited an early burst of spikes with a mean latency of 16 +/- 1.2 ms. From a spontaneous discharge rate of 5.2 +/- 1.2 spikes/s, neuronal activity increased by 2.9 +/- 0.3 spikes/stimulus. In addition to an early peak, 15 neurons (25%) exhibited a late burst of spikes with a latency of 182 +/- 12.9 ms; neuronal activity increased by 5.0 +/- 1.3 spikes/stimulus. Duration of the late peak (130 +/- 18.5 ms) was longer than for the early peak (18 +/- 0.7 ms), but threshold voltages for eliciting each peak were comparable. Sixteen of 29 spontaneously active neurons exhibited a postexcitatory depression of activity that lasted for 163 +/- 19.1 ms. All but one tested neuron in RO responded to stimulation of sympathetic afferents, but 65% of neurons in RM responded to this stimulus. 3. In response to vagal afferent stimulation, 19% of 57 neurons exhibited inhibition only, 11% were only excited, and 9% were either excited or inhibited, depending on the stimulus paradigm used; the remaining 61% of neurons were unresponsive. From a spontaneous rate of 7.9 +/- 3.8 spikes/s, excited cells increased their discharge rate by 1.6 +/- 0.3 spikes/stimulus. Activity of inhibited cells was reduced from 21.3 +/- 5.8 to 7.8 +/- 3.1 spikes/s. The conditioning-test (CT) technique was used to assess 11 neurons' responses. Stellate ganglion stimulation was the test stimulus, and vagal stimulation the conditioning stimulus. Vagal stimulation reduced the neuronal responses to stellate ganglion stimulation by an average of 50% with a CT interval of 60-100 ms, and cell responses returned to control after 300 ms. With spontaneous cell activity, low frequencies of vagal stimulation were generally excitatory, and high frequencies (10-20 Hz) inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mechanical response properties of A and C primary afferent neurons innervating the rat intracranial dura

The intracranial dura receives a small-fiber sensory innervation from the trigeminal ganglion that is thought to be involved in some types of headaches, including migraine. Mechanical response properties of dural afferent neurons were examined to investigate variation across the population in the properties of threshold, slope, adaptation, and incidence of mechanosensitivity. Dural afferent neurons were recorded in the trigeminal ganglion of urethan-anesthetized rats and were identified by their constant-latency response to dural shock. Neurons were classified as fast A (>5 m/s), slow A (5 >or= conduction velocity (CV) >or= 1.5 m/s), or C (<1.5 m/s), based on response latency to dural shock. Mechanical receptive fields were identified by stroking or indenting the outer surface of the dura. Stimulus-response curves were obtained from responses to 2-s constant-force indenting stimuli of graded intensities delivered to the dural receptive field with a servo force-controlled mechanical stimulator. The slow A population had the highest percentage of mechanosensitive units (97%) as well as the highest slopes and the lowest thresholds. Thus by all three criteria, the slow As had the highest mechanosensitivity. Conversely, the fast A population had the lowest mechanosensitivity in that it had the lowest percentage of mechanosensitive units (66%), the lowest slopes, and the highest thresholds. The C population was intermediate with respect to all three properties but was much more similar to the slow As than to the fast As. All three fiber classes showed a negative correlation between slope and threshold. The majority of neurons showed a slowly adapting response to a maintained 2-s stimulus. Adapting neurons could be subdivided based on whether the fitted exponential curve decayed to zero or to a nonzero plateau; the latter group contained the most sensitive neurons in that they had the lowest thresholds and highest slopes. Nonadapting neurons generally had lower initial firing rates than adapting neurons. Fast A neurons exhibited greater and more rapid adaptation than slow A and C neurons. Neurons with the lowest slopes, regardless of CV, had relatively rapid adaptation. The more slowly conducting portion of the C population was distinguished from the other C neurons by a number of properties: more mechanically insensitive neurons, higher thresholds, and more nonadapting neurons. These differences in mechanical response properties may be related in part to differences in membrane currents involved in impulse generation that have been described in subpopulations of dorsal root ganglion cells.     

Efferent neurons and suspected interneurons in second somatosensory cortex of the awake rabbit: receptive fields and axonal properties.

1. Receptive-field properties of antidromically identified efferent neurons within the representation of vibrissae and sinus hairs above the mouth were examined in secondary somatosensory cortex (S-2) of fully awake adult rabbits. Efferent neurons studied included callosal neurons (CC neurons, n = 88), ipsilateral corticocortical neurons (C-IC neurons, n = 51) that project to primary somatosensory cortex (S-1), and corticofugal neurons of layer 5 (CF-5 neurons, n = 63) and layer 6 (CF-6 neurons, n = 42) that project to and/or beyond the thalamus. Appropriate collision tests demonstrated that substantial numbers of corticocortical efferent neurons (21 of 113 tested) project an axon to both the corpus callosum and to ipsilateral S-1. 2. Suspected interneurons (SINs, n = 62) were also studied. These neurons were not activated antidromically from any stimulus site but did respond synaptically to electrical stimulation of the ventrobasal (VB) thalamus with a burst of three or more spikes at frequencies of 600 to greater than 900 Hz. Most of these neurons also responded synaptically to stimulation of S-1 and the corpus callosum. The action potentials of these neurons were much shorter (mean, 0.49 ms) than those of efferent neurons (mean, 1.01 ms). 3. CF-5 neurons differed from CC, C-IC, and CF-6 neurons in their spontaneous firing rates, axonal properties, and receptive-field properties. Whereas CF-5 neurons had a mean spontaneous firing rate of 5.7 spikes/s, CC, C-IC, and CF-6 neurons all had mean values of less than 1/s. Axonal conduction velocities of CF-5 neurons were much higher (mean, 11.90 m/s) than either CC (mean, 2.63 m/s), C-IC (mean, 0.86 m/s), or CF-6 (mean, 1.73 m/s) neurons. A decrease in antidromic latency (the "supernormal" period), which was dependent on prior impulse activity, was seen in most CC, C-IC, and CF-6 neurons but was minimal or absent in CF-5 neurons of comparable conduction velocity. Although all CF-5 neurons responded to peripheral sensory stimulation, many CC (52%), C-IC (49%), and CF-6 (55%) neurons did not. CC and CF-6 neurons that did not respond to sensory stimulation had significantly lower axonal conduction velocities and spontaneous firing rates than those that responded to such stimulation. Whereas no CC, C-IC, or CF-6 neuron responded synaptically to callosal stimulation, 43% of CF-5 neurons (and 78% of SINs) did so respond. Similar differences in synaptic responsivity to stimulation of S-1 were seen in these populations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dendritic sodium spikelets and low-threshold calcium spikes in turtle olfactory bulb granule cells

Active dendritic membrane properties were investigated by whole cell recordings from adult turtle olfactory bulb granule cells. The laminar structure of the olfactory bulb allowed differential polarization of the distal apical dendrites versus the somatic part of the cells by an external electric field. Dendritic depolarization evoked small (approximately 10 mV) all-or-none depolarizing events of approximately 10-ms duration. These spikelets often occurred in bursts at high frequency (< or = 250 Hz); they were present despite the application of synaptic and gap junction antagonists, but were abolished by TTX and intracellularly applied QX314. The spikelets were interpreted as attenuated sodium spikes initiated in different branches of the granule cells dendrites. They occurred spontaneously, but could also be evoked by excitatory postsynaptic potentials (EPSPs) to the distal dendrites. Spikelets initiated by distal excitation could function as prepotentials for full sodium spikes, in part depending on the level of proximal depolarization. Somatic depolarization by the electric field evoked full sodium spikes as well as low-threshold calcium spikes (LTSs). Calcium imaging revealed that the electrophysiologically identified LTS evoked from the soma was associated with calcium transients in the proximal and the distal dendrites. Our data suggest that the LTS in the soma/proximal dendrites plays a major role in boosting excitability, thus contributing to the initiation of sodium spiking in this compartment. The results furthermore suggest that the LTS and the sodium spikes may act independently or cooperatively to regulate dendritic calcium influx.     

Mode of activation of hippocampal pyramidal cells by excitatory synapses on dendrites

Summary Following selective activation of four afferent paths that terminate exclusively on dendrites, only a small proportion of pyramidal cells in the hippocampal fields CA1 and CA3 discharged impulses. Following a single afferent volley, an EPSP was never observed even in cells synaptically excited. On tetanic stimulation (about 10/sec), a large EPSP developed, but this was not a prerequisite for an action potential.Studies of the extracellular field potentials corresponding to the EPSP and the population spike potential, indicated that the EPSP was generated across the dendritic membrane and that the spike was initiated in the neighbouring part of the dendritic tree, propagating from there along the thicker dendrites towards the soma. This conduction had an average velocity of 0.4m/sec, and, presumably, a relatively low safety factor.In certain cases, the intrasomatic electrode recorded small all-or-nothing spikes which presumably were generated in the dendritic tree. These small spikes (D-spikes) invaded the soma only if assisted by some additional depolarization, for example by frequency potentiation of excitatory synapses.The results indicate two functional types of pyramidal dendrites, the conducting and the synaptic type.     

Contribution of potassium conductances to a time-dependent transition in electrical properties of a cockroach motoneuron soma.

Contribution of potassium conductances to a time-dependent transition in electrical properties of a cockroach motoneuron soma. The cell body of the cockroach (Periplaneta americana) fast coxal depressor motoneuron (Df) displays a time-dependent change in excitability. Immediately after dissection, depolarization evokes plateau potentials, but after several hours all-or-none action potentials are evoked. Because K channel blockers have been shown to produce a similar transition in electrical properties, we have used current-clamp, voltage-clamp and action-potential-clamp recording to elucidate the contribution of different classes of K channel to the transition in electrical activity of the neuron. Apamin had no detectable effect on the neuron, but charybdotoxin (ChTX) caused a rapid transition from plateau potentials to spikes in the somatic response of Df to depolarization. In neurons that already produced spikes when depolarized, ChTX increased spike amplitude but did not increase their duration nor decrease the amplitude of their afterhyperpolarization. 4-Aminopyridine (4-AP) (which selectively blocks transient K currents) did not cause a transition from plateau potentials to spikes but did enhance oscillations superimposed on plateau potentials. When applied to neurons that already generated spikes when depolarized, 4-AP could augment spike amplitude, decrease the latency to the first spike, and prolong the afterhyperpolarization. Evidence suggests that the time-dependent transition in electrical properties of this motoneuron soma may result, at least in part, from a fall in calcium-dependent potassium current (IK,Ca), consequent on a gradual reduction in [Ca2+ ]i. Voltage-clamp experiments demonstrated directly that outward K currents in this neuron do fall with a time course that could be significant in the transition of electrical properties. Voltage-clamp experiments also confirmed the ineffectiveness of apamin and showed that ChTX blocked most of IK,Ca. Application of Cd2+ (0.5 mM), however, caused a small additional suppression in outward current. Calcium-insensitive outward currents could be divided into transient (4-AP-sensitive) and sustained components. The action-potential-clamp technique revealed that the ChTX-sensitive current underwent sufficient activation during the depolarizing phase of plateau potentials to enable it to shunt inward conductances. Although the ChTX-sensitive conductance apparently makes little contribution to spike repolarization, the ChTX-resistant IK,Ca does make a significant contribution to this phase of the action potential. The 4-AP-sensitive current began to develop during the rising phase of both action potentials and plateau potentials but had little effect on the electrical activity of the neuron, probably because of its relatively small amplitude.     

Identification and characterization of two functionally distinct groups of spinal cord-projecting paraventricular nucleus neurons with sympathetic-related activity

Activation of spinal cord-projecting neurons of the hypothalamic paraventricular nucleus (PVN) has been implicated in a host of sympathetic nervous system functions. Here, we report two distinct activity patterns among electrophysiologically identified PVN spinal neurons that may contribute to the varied functional responses elicited by PVN activation. Extracellular single-unit recording was performed in anesthetized rats, and PVN neurons were antidromically identified by electrical stimulation of the spinal cord (T1-3 or T10-12). Axonal conduction velocity was determined for each identified neuron and revealed two distinct groups of cells, designated Group I (n=19) and Group II (n=34). Conduction velocity was significantly (P<0.01) different between Group I (3.67+/-0.29 m/s) and Group II (0.45+/-0.01 m/s) cells and indicates that axons of Group I cells are larger and/or more heavily myelinated than those of Group II, which appear to be unmyelinated. The majority of Group I (15/19: 79%) and Group II (23/34: 68%) cells discharged spontaneously. Basal firing rates were significantly different between groups (Group I: 2.7+/-0.85 versus Group II: 1.8+/-0.64 spikes s(-1); P<0.05). Spike-triggered averaging of renal sympathetic nerve activity revealed sympathetic-related discharge among a majority of Group I (11/15:73%) and Group II (17/23: 74%) neurons. In addition, seven of 11 Group I cells showed cardiac-related discharge. Pulse-rhythmic discharge was not detectable in any Group II cells tested (n=17). Among 11 Group I cells tested for barosensitivity, discharge in eight (73%) was graded by changes in mean arterial pressure. None of the 16 Group II cells tested for arterial pressure sensitivity responded.We conclude that the PVN spinal pathway is comprised of at least two functionally distinct cell types. The response profile and activity patterns of Group I cells suggest involvement in regulating vasomotor components of sympathetic outflow. By comparison, the activity of Groups II cells suggests a possible role in non-vasomotor sympathetic control.     

Responses to taste stimulation in the ventroposteromedial nucleus of the thalamus in rats

Extracellular action potentials were recorded from 73 neurons in the parvicellular division of the ventroposteromedial (VPMpc) nucleus of the thalamus of anesthetized Wistar rats during gustatory, thermal, and tactile stimulation of the whole oral cavity. The stimulus array consisted of 16 room-temperature (23 degrees C) sapid stimuli, distilled water at three temperatures (0, 23, and 37 degrees C), and 0.1 M NaCl at three temperatures (0, 23, and 37 degrees C). Among all 151 neurons isolated in VPMpc, 9% responded exclusively to taste, 33% to taste and temperature, none to taste and touch, but 6% to all three modalities. Discharge rates evoked by the basic tastants were 13.8 +/- 1.6 (SD) spikes/s for 0.1 M NaCl, 9.3 +/- 1.4 spikes/s for 0.01 M HCl, 5.1 +/- 0.9 spikes/s for 0.5 M sucrose, and 4.3 +/- 0.6 spikes/s for 0.01 M quinine HCl. Water evoked mean responses at 0, 23, and 37 degrees C of 9.9 +/- 1.5, 0.6 +/- 0.4, and 1.3 +/- 0.9 spikes/s, respectively. The mean firing rate evoked by 37 and 0 degrees C NaCl was 15.0 +/- 2.4 and 17.0 +/- 2.8 spikes/s, respectively. The exponent of the NaCl concentration-response power function was 0.39. Thalamic taste cells were broadly tuned. The mean breadth-of-tuning coefficient for these 73 gustatory cells was 0.79 +/- 0.02. Two cells responded predominantly with inhibition, which accounted for the majority of inhibitory responses. The taste neurons were statistically divisible into three groups: sodium-oriented (n = 40), acid-oriented (n = 12), and sugar-oriented (n = 17). Four additional bitter-oriented neurons were not closely enough related to be defined as a group and were considered outliers. The sodium-oriented group could be divided into three statistically distinct subgroups, differing in the specificity of their responses to NaCl. With respect to polymodal sensitivity, spontaneous rate, evoked response rates, signal-to-noise ratio, proportions of cells responding best to basic tastants, taste neuron groups, taste spaces, and temporal responses, VPMpc neurons have characteristics that are intermediate between those of parabrachial and cortical gustatory neurons.     

Temperature neurons in the crotaline trigeminal ganglia.

1. Intrasomal recordings were made with microelectrodes from 153 warm (infrared) neurons in the trigeminal ganglia of 36 crotaline snakes, Trimeresurus flavoviridis. Background discharges were observed at room temperature. The 153 warm neurons were classified into two groups: 81 were sensitive to less than or equal to 10 mg of von Frey hair mechanical stimulation (warm T + M neuron), and 72 were insensitive to up to 100 mg or more of mechanical stimulation (warm T neuron). For T + M and T neurons the receptive fields were all located in the pit organ. The mechanically sensitive field of warm T + M neurons located within the infrared receptive field on the pit membrane was less than 1 mm in diameter, and there was only one field per neuron. 2. Electrophysiological parameters were measured. These measurements included membrane potential, action potential amplitude, time of peaking, time duration at the resting membrane potential level, afterhyperpotential (AHP) height and AHP time to half-decay, and maximum rates of depolarization and repolarization. No difference in action potential parameters between the means of these two submodality groups was observed. 3. Intracellular horseradish peroxidase (HRP) labeling was used for defining the warm neuron profile. The somata of warm T and warm T + M neurons and T- or Y-shaped bifurcations of the axon were observed in the ganglion. At the bifurcation point, nodes of Ranvier were observed, but without broad triangular expansion. Diameters of the central axons were thinner than those of the peripheral or stem axons. There were no differences between the mean diameters of the two submodalities. 4. The central axons of warm T and T + M neurons projected to the lateral descending nucleus of the trigeminal nerve (LTTD). Their synaptic boutons were found in the LTTD. No branching of the axons to the principal sensory nucleus or the descending nucleus of the trigeminal nerve was found. These results were the same for six warm T and eight warm T + M neurons. 5. Conduction velocities of the peripheral fibers were measured by stimulating superficial branches of the maxillary nerve electrically. Three groups of conduction velocity were identified in the compound potentials. The conduction velocity of the peak action potential of the warm T fibers was 6.9 +/- 1.2 (SD) m/s (n = 18), that of the T + M fibers 6.7 +/- 0.9 m/s (n = 23). These fell into the second group of the compound potentials.(ABSTRACT TRUNCATED AT 400 WORDS)     

Peptidergic inhibition of cholinergic transmission in bullfrog sympathetic ganglia

Intracellular and voltage-clamp recordings were made from sympathetic B neurons to investigate an interaction between peptidergic and cholinergic responses in bullfrog sympathetic ganglia. Stimulations of both 3rd-5th (0.2 Hz) and 8th (30 Hz) spinal nerves evoked the fast excitatory postsynaptic potential (EPSP) superimposed with the late slow EPSP at the same sympathetic neuron. The amplitude of fast EPSPs was decreased during the course of the late slow EPSP in a majority of sympathetic neurons. The mean depression of the fast EPSP amplitude was 51 +/- 4% (n = 24). The quantal content of the fast EPSP was also depressed by 54 +/- 3% (n = 10) during the late slow EPSP. Acetylcholine-induced depolarization (ACh potential) and current (ACh current) produced by an ionophoretic application of ACh were not reduced during the late slow EPSP. Bath-application of LH-RH (40 nM-4 microM) depressed the fast EPSP in a concentration-dependent manner; at a concentration of 1 microM, it produced a 63 +/- 8% (n = 8) depression of the quantal content of the fast EPSP. LH-RH (1-4 microM) depressed the frequency of the miniature (M) EPSPs by 25 +/- 4% (n = 5) of control. Antagonists for luteinizing hormone-releasing hormone (LH-RH) receptor, [D-Phe2,6, Pro3]-LH-RH and [D-pGlu1, D-Phe2, D-Trp3,6]-LH-RH, prevented the presynaptic inhibition of the fast EPSP induced by LH-RH. These results suggest that the fast EPSP is depressed during the late slow EPSP by decreasing the evoked release of ACh from presynaptic nerve terminals in bullfrog sympathetic ganglia.