Response properties of mouse trigeminal ganglion neurons

We used controlled whisker deflections to examine the response properties of 208 primary afferent neurons in the trigeminal ganglion of adult mice. Proportions of rapidly adapting (RA, 47%) and slowly adapting (SA, 53%) neurons were equivalent, and most cells had low or no spontaneous activity. We quantified angular tuning and sensitivity to deflection amplitude and velocity. Both RA and SA units fired more frequently to larger deflections and faster deflections, but RA units were more sensitive to differences in velocity whereas SA units were more sensitive to deflection amplitudes. Almost all neurons were tuned for deflection angle, and the average response to the maximally effective direction was more than fourfold greater than the average response in the opposite direction; SA units were more tuned than RA units. Responses of primary afferent whisker-responsive neurons are qualitatively similar to those of the rat. However, average firing rates of both RA and SA neurons in the mouse are less sensitive to differences in deflection velocity, and RA units, unlike those in the rat, display amplitude sensitivity. Subtle observed differences between mice and rats may reflect greater mechanical compliance in mice of the whisker hairs and of the tissue in which they are embedded.     

Adaptation of trigeminal ganglion cells to periodic whisker deflections

Trigeminal ganglion neurons in adult rats adapt to periodic whisker deflections in the range of 1–40?Hz, manifested as a reduction in spike counts to progressively later stimuli in a train of pulsatile or sinusoidal deflections. For high velocity, pulsatile deflections, adaptation is time- and frequency-dependent; as in the case of thalamic and cortical neurons, adaptation is greater at higher stimulus frequencies. With slower velocity, sinusoidal movements, trigeminal ganglion cells differ from central neurons, however, by exhibiting strong adaptation even at low frequencies. For both types of stimuli, effects in trigeminal ganglion neurons were more pronounced in rats maintained during the recording session under neuromuscular blockade than in non-paralysed animals. Results are consistent with previous findings in other systems that frequency-dependent adaptation of cutaneous primary afferent neurons is affected by mechanical properties of the skin. Such effects are likely to vary depending on the nature of the whisker stimuli and physiological states that affect skin viscoelasticity.     

培养的大鼠三叉神经节细胞钙激活钾通道的氧化性调节

目的：研究氧化还原药物对三叉神经节细胞离子通道的调节作用。方法：采用全细胞膜片钳电生理方法,记录氧化还原药物对三叉神经节细胞大电导钙激活钾通道（BKca）的影响。结果：蛋氨酸特异性氧化剂chloramine-T（Ch—T）1mmol／L可轻微增加通道电流幅值,但该作用不能被半胱氨酸还原剂1,4-dithio-DL-threitol（DTT）所逆转。相反,半胱氨酸特异性氧化剂5,5’-dithio-bis（2-nitribenzoic acid）（DTNB）500μmol／L降低BKCa的电流幅值,此作用可被DTT 2mmol／L所逆转。结论：ROS通过氧化调节BKCa通道而参与三叉神经节细胞的功能调节,BKCa通道在氧化应激相关性生理、病理状态下起重要的调节作用。     

Response of trigeminal ganglion neurons to thermal stimulation of the beak in pigeons

Summary The activity of neurons from the trigeminal ganglion of pigeons have been recorded while cooling or warming the beak. Thermosensitive neurons were seldom compared with mechanosensitive units. From a total of 16 thermosensitive neurons, 13 were excited by cooling and 3 by warming. The impulse frequency strongly depended on temperature. At constant temperatures, constant firing rates were established. The static curves of cold-sensitive units showed, that with decreasing temperature a nearly linear rise in firing rate occurred between about 36 °C and 20 °C. One quantified, warm-sensitive neuron showed, with increasing temperature, a nearly linear rise between about 35 °C and 44 °C. Sudden cooling or warming caused no pronounced overshoot as in mammals. Six cold-sensitive neurons were totally inhibited by rewarming as were 2 warm-sensitive units by cooling. No comparable influence of temperature on the discharge rate of some slowly-adapting mechanoreceptors (pressure stimulus) was exhibited.Supported by the Deutsche Forschungsgemeinschaft (SFB Bionach).     

Whisker plucking alters responses of rat trigeminal ganglion neurons

Whisker plucking in developing and adult rats provides a convenient method of temporarily altering tactile input for the purposes of studying experience-dependent plasticity in the somatosensory cortex. Yet, a comprehensive examination of the effect of whisker plucking on the response properties of whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We used extracellular single unit recordings to examine responses of NVg neurons to controlled whisker stimuli in three groups of animals: (1) rats whose whiskers were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at 21 days of age; and (3) control animals. After at least 3 weeks of whisker re-growth, NVg neurons in plucked rats displayed normal, single whisker receptive fields and could be characterized as slowly (SA) or rapidly adapting (RA). The proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and RA NVg neurons in plucked rats displayed normal response latencies and angular tuning but abnormally large responses to whisker movement onsets and offsets. SA neurons were affected to a greater extent than RA neurons. The effect of whisker plucking was more pronounced in animals whose whiskers were plucked repeatedly during development than in rats whose whiskers were plucked once. Individual neurons in plucked animals displayed abnormal periods of prolonged rhythmic firing following deflection onsets and aberrant bursts of activity during the plateau phase of the stimulus. These results indicate that whisker plucking exerts a long-term effect on responses of trigeminal ganglion neurons to peripheral stimulation.     

Responses of cultured rat trigeminal ganglion neurons to bitter tastants

The initial steps in taste and olfaction result from the activation by chemical stimuli of taste receptor cells (TRCs) and olfactory receptor neurons (ORNs). In parallel with these two pathways is the chemosensitive trigeminal pathway whose neurons terminate in the oral and nasal cavities and which are activated by many of the same chemical stimuli that activate TRCs and ORNs. In a recent single unit study we investigated the responses of rat chorda tympani and glossopharnygeal neurons to a variety of bitter-tasting alkaloids, including nicotine, yohimbine, quinine, strychnine and caffeine, as well as capsaicin, the pungent ingredient in hot pepper. Here we apply many of these same compounds to cultured rat trigeminal ganglion (TG) neurons and measure changes in intracellular calcium [Ca2+]i to determine whether TG neurons will respond to these same compounds. Of the 89 neurons tested, 34% responded to 1 mM nicotine, 7% to 1 mM caffeine, 5% to 1 mM denatonium benzoate, 22% to 1 mM quinine hydrochloride, 18% to 1 mM strychnine and 55% to 1 microM capsaicin. These data suggest that neurons from the TG respond to the same bitter-tasting chemical stimuli as do TRCs and are likely to contribute information sent to the higher CNS regarding the perception of bitter/irritating chemical stimuli.      

Effects of low concentrations of tetradotoxin on rat trigeminal ganglion neurons

Voltage clamping and intracellular perfusion methods were used to investigate ionic currents produced by depolarizing shifts of –120 mV from holding potential during experiments on neurons isolated from the trigeminial ganglion of one-month-old rats. It was found that tetradotoxin at low (external) concentrations of 10^–12–10¹⁰ M produced an increase in the amplitude and alternations in the kinetics of inward ionic currents. Similar effects were observed in 8 test cells out of 29. The extent to which the increase in the amplitude of inward ionic currents depended on concentration level could be described by Langmuir's isotherm, with a dissociation constant of the order of 5·10^–12 M. No such tetrodotoxin effects were observed when chloride ions were replaced by a non-penetrating anion in the intracellular solution. It is suggested that tetrodotoxin-sensitive channels exist in the neuronal membrane of the rat trigeminal ganglion, letting through chloride ions during depolarization of the membrane.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 6, pp. 723–729, November–December, 1986.     

Organization and physiology of posterior lateral line afferent neurons in larval zebrafish

The lateral line system of larval zebrafish can translate hydrodynamic signals from the environment to guide body movements. Here, I demonstrate a spatial relationship between the organization of afferent neurons in the lateral line ganglion and the innervation of neuromasts along the body. I developed a whole cell patch clamp recording technique to show that afferents innervate multiple direction-sensitive neuromasts, which are sensitive to low fluid velocities. This work lays the foundation to integrate sensory neuroscience and the hydrodynamics of locomotion in a model genetic system.     

Response properties of periodontal mechanosensitive neurons in the trigeminal spinal tract nucleus of the cat.

Periodontal mechanosensitive (PM) units were recorded from the trigeminal spinal tract nucleus (Vst) of the cat. The Vst is divided into three subnuclei: oralis (Vo), interpolaris (Vi), and caudalis (Vc). The receptive fields of PM units in Vo and Vi were arranged in a dorsoventral sequence in the mandibular to maxillary divisions, and those in Vc were arranged in a mediolateral sequence. The majority of Vo units were single-tooth ones, whereas more than half the Vi units and all the Vc ones were multitooth units. The PM units in each subnucleus were predominantly responsive to canine tooth stimulation. Most of the PM units in Vo and Vi gave sustained responses to pressure applied to the tooth, were directionally selective, and were most actively excited by canine tooth stimulation in the caudomedial or rostrolateral direction. Vc units, however, were transient. The threshold intensity for firings by canine tooth stimulation was less than 0.05 N. These findings indicate that only the response properties of PM units in the rostral part of Vst resemble those of the trigeminal main sensory nucleus neurons and primary afferent nerves.     

Epoxyeicosatrienoic acids are endogenous regulators of vasoactive neuropeptide release from trigeminal ganglion neurons

Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. We previously described the expression of cytochrome P450-2J epoxygenase in rat trigeminal ganglion neurons and that EETs signaling is involved in cerebrovascular dilation resulting from perivascular nerve stimulation. In this study, we evaluate the presence of the EETs signaling pathway in trigeminal ganglion neurons and their role in modulating the release of calcitonin gene-related peptide (CGRP) by trigeminal ganglion neurons. Liquid chromatography tandem mass spectrometry identified the presence of each of the four EETs regio-isomers within primary trigeminal ganglion neurons. Stimulation for 1 h with the transient receptor potential vanilloid-1 channel agonist capsaicin (100 nmol/L) or depolarizing K(+) (60 mmol/L) increased CGRP release as measured by ELISA. Stimulation-evoked CGRP release was attenuated by 30 min pre-treatment with the EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 μmol/L). K(+) stimulation elevated CGRP release 2.9 ± 0.3-fold above control levels, whereas in the presence of 14,15-EEZE K(+)-evoked CGRP release was significantly reduced to 1.1 ± 0.2-fold above control release (p < 0.01 anova, n = 6). 14,15-EEZE likewise attenuated capsaicin-evoked CGRP release from trigeminal ganglion neurons (p < 0.05 anova, n = 6). Similarly, pre-treatment with the cytochrome P450 epoxygenase inhibitor attenuated stimulation-evoked CGRP release. These data demonstrate that EETs are endogenous constituents of rat trigeminal ganglion neurons and suggest that they may act as intracellular regulators of neuropeptide release, which may have important clinical implications for treatment of migraine, stroke and vasospasm after subarachnoid hemorrhage.     

Responses of rat trigeminal ganglion neurons to movements of vibrissae in different directions

The response properties of 123 trigeminal ganglion neurons were studied, using controlled whisker deflections in different directions. When the distal end of the whisker was initially displaced 5.7 degrees (1 mm) from its neutral position, 81% of the cells responded with statistically more spikes/stimulus to movements in one to three of eight cardinal (45 degrees increment) directions than to the others. The more directionally selective the cell, the more vigorous was its response. On the basis of statistical criteria, 75% of the cells were classified as slowly adapting, 25% as rapidly adapting. A number of quantitative analyses indicated that slowly adapting units respond more selectively than rapidly adapting cells to the direction of whisker movement. Differences in directional sensitivities of rapidly and slowly adapting cells appear to parallel differences between their putative mechanoreceptive endings and the relationships between those endings and the vibrissa follicle's structure. Comparisons between the response properties of peripheral and central neurons in the vibrissa-lemniscal system indicate that the afferent neural signal is progressively and substantially transformed by mechanisms that function to integrate information from different peripheral receptors and from different, individual vibrissae.     

Responses of trigeminal ganglion neurons during natural whisking behaviors in the awake rat

Rats use their whiskers to locate and discriminate tactile features of their environment. Mechanoreceptors surrounding each whisker encode and transmit sensory information from the environment to the brain via afferents whose cell bodies lie in the trigeminal ganglion (Vg). These afferents are classified as rapidly (RA) or slowly (SA) adapting by their response to stimulation. The activity of these cells in the awake behaving rat is yet unknown. Therefore, we developed a method to chronically record Vg neurons during natural whisking behaviors and found that all cells exhibited (1) no neuronal activity when the whiskers were not in motion, (2) increased activity when the rat whisked, with activity correlated to whisk frequency, and (3) robust increases in activity when the whiskers contacted an object. Moreover, we observed distinct differences in the firing rates between RA and SA cells, suggesting that they encode distinct aspects of stimuli in the awake rat.     

谷氨酸对原代培养海马神经元的兴奋特性

目的:探索谷氨酸对培养大鼠海马神经元的兴奋特性.方法:分离及培养1日龄SD大鼠海马神经元,第9～15 d用膜片钳检测不同浓度谷氨酸对神经元兴奋特性,包括细胞膜电位、去极化/动作电位的影响.结果:谷氨酸降低海马神经元静息膜电位,诱发去极化/动作电位,高浓度谷氨酸处理组神经元的静息膜电位比低浓度组降低显著;100μmol/L谷氨酸长时间处理组的神经细胞膜电位显著低于短时间处理组.结论:谷氨酸对海马神经元兴奋性有浓度和时间依赖性.     

背根神经节神经元阿片受体和离子通道的研究进展

阿片及阿片受体与外周神经系统镇痛机制的研究,随着分子生物学技术的发展,已在受体的分子结构、形态学、分子药理学、离子通道和细胞内信号转导系统等方面取得了显著进展。μ、δ、κ阿片受体分子结构上的部分差异决定了它们各自的功能特征。三种受体在初级感觉神经元分布的比例不同,但都能介导细胞Ｃａ＾２＋通道的抑制和Ｋ＾＋电流增加及减少。阿片受体和通道之间由多种第二信使系统偶联。分子药理学研究表明它们还存在亚型受体     

大鼠三叉神经节不同直径神经元ATP-激活电流的特征

目的:探讨大鼠三叉神经节不同直径神经元ATP-激活电流的特征。方法:应用全细胞膜片钳技术进行实验。结果:①92.3%(60/65)的细胞对ATP敏感,有反应的细胞可记录到三种型式的ATP-激活电流:快速激活快速失活型(Fast type,F型)、快速激活缓慢失活型(Intermediate type,I型)和缓慢激活缓慢失活型(Slowtype,S型)。三种电流均具有浓度依赖性。②小直径的细胞多表现为F型特征,大直径的细胞多表现为S型特征,而中等大小的细胞多表现为I型特征。③动力学特征:三种类型的ATP激活电流上升相从10%到90%的时间:F型:(33.6±4.5)ms;Ⅰ型:(62.2±9.9)ms;S型:(302.1±62)ms。去敏感相从10%到90%的时间:F型:(399.4±58.2)ms;S型:>500ms。④I-V曲线:三种电流均表现为内向整流的特性,而且翻转电位均为0~5mV。⑤量-效关系:Ⅰ型的量-效曲线居中间,F型的下移,S型的上移,三种类型电流量-效曲线的EC50非常接近。结论:三种型式的ATP-激活电流可能是由不同亚单位组合的P2X受体各亚型所介导,这些亚型分布于不同大小的三叉神经节神经元,从而传导不同的信息。     

Calcitonin gene-related peptide enhances release of native brain-derived neurotrophic factor from trigeminal ganglion neurons

Activity-dependent plasticity in nociceptive pathways has been implicated in pathomechanisms of chronic pain syndromes. Calcitonin gene-related peptide (CGRP), which is expressed by trigeminal nociceptors, has recently been identified as a key player in the mechanism of migraine headaches. Here we show that CGRP is coexpressed with brain-derived neurotrophic factor (BDNF) in a large subset of adult rat trigeminal ganglion neurons in vivo. Using ELISA in situ, we show that CGRP (1-1000 nM) potently enhances BDNF release from cultured trigeminal neurons. The effect of CGRP is dose-dependent and abolished by pretreatment with CGRP receptor antagonist, CGRP(8-37). Intriguingly, CGRP-mediated BDNF release, unlike BDNF release evoked by physiological patterns of electrical stimulation, is independent of extracellular calcium. Depletion of intracellular calcium stores with thapsigargin blocks the CGRP-mediated BDNF release. Using transmission electron microscopy, our study also shows that BDNF-immunoreactivity is present in dense core vesicles of unmyelinated axons and axon terminals in the subnucleus caudalis of the spinal trigeminal nucleus, the primary central target of trigeminal nociceptors. Together, these results reveal a previously unknown role for CGRP in regulating BDNF availability, and point to BDNF as a candidate mediator of trigeminal nociceptive plasticity.     

Classification of voltage-dependent Ca2+ channels in trigeminal ganglion neurons from neonatal rats

We examined the subtypes and characteristics of the Ca(2+) channel in small (diameter < 30 microm) trigeminal ganglion (TG) neurons from neonatal rats by means of whole cell patch clamp techniques. There were two current components, low-voltage activated (LVA) and high-voltage activated (HVA) I(Ba), with different activation ranges and waveforms. LVA I(Ba) elicited from a depolarizing step pulse at a holding potential (HP) of -80 mV was inhibited by 0.25 mM amiloride (62%), which did not produce any significant inhibition of the peak amplitude of HVA I(Ba). The application of 0.5 mM amiloride inhibited 10% of the HVA I(Ba). The LVA I(Ba) was also reduced by changing the HP from -80 to -60 mV (61%), and under these conditions the peak amplitude of HVA I(Ba) did not change significantly. In addition, HVA I(Ba) and LVA I(Ba) showed marked differences in their inactivation properties. Experiments with several Ca(2+) channel blockers revealed that on average, 26% of the HVA I(Ba) was nifedipine (10 microM) sensitive, 55% was sensitive to omega-conotoxinGVIA (1 microM), 4% was blocked by omega-agatoxinIVA (1 microM), and the remainder of the current that was resistant to the co-application of all three Ca(2+) channel blockers was 15% of the total current. These results suggest that the application of amiloride and the alteration of the holding potential level can discriminate between HVA and LVA Ba(2+) currents in TG neurons, and that TG neurons expressed T-, L-, N-, P-/Q- and R-type Ca(2+) channels.