外侧臂旁核神经元对穹隆下器逆向刺激和孤束核顺向刺激的反应

细胞外记录大鼠外侧臂旁核(LPBN)神经元单位放电,观察了刺激穹隆下器(SFO)在记录单位诱发的逆向反应和静脉注射新福林兴奋外周压力感受器和刺激孤束核(NTS)减压区诱发的顺向反应。实验发现:刺激 SFO,9.9%(15/151)的 LPBN 神经元有逆向反应。静脉注射新福林,40.7%(22/54)的 LPBN 神经元有抑制反应,27.8%(17/54)有兴奋反应。刺激 NTS,55.6%(94/169)的 LPBN 神经元呈现顺向兴奋反应;22.5%(38/169)呈现顺向抑制反应。观察静脉注射新福林对 SFO 刺激有逆向反应的 LPBN 神经元自发放电的影响,在两个受试单位均见抑制反应。观察刺激 NTS 对逆向反应单位自发放电的影响,在8个受试单位中,6个呈兴奋反应;2个呈抑制反应。以上结果表明:LPBN 接受来自 NTS 的兴奋性或抑制性压力感受性传入,并把这种信息经 LPBN-SFO 直接通路传输到 SFO。     

孤束核内微电泳NPY对压力感受性和化学感受性激活神经元放电的影响

本实验观察了孤束核（ＮＴＳ）内微电泳神经肽Ｙ（ＮＰＹ）对压力感受性刺激和化学感受性刺激反应神经元放电的影响。在６２个单位放电中,其中对微电泳ＮＰＹ表现兴奋反应３４个单位,１９个单位表现抑制反应,无反应单位９个。微电泳ＮＰＹ对压力感受性刺激呈兴奋反应的单位主要表现兴奋作用（１６／２１）,对抑制反应单位主要表现抑制作用（７／１１）,对化学感受性刺激的兴奋单位（８／１４）和抑制单位（５／９）均主要以兴奋为主。     

脑内血管紧张素Ⅱ系统在穹窿下器升压反应中的作用

文献报道脑内存在血管紧张素Ⅱ系统。与此一致,本工作用氨基甲酸乙脂麻醉、箭毒制动、人工呼吸的大鼠观察到：（１）穹窿下器（ＳＦＯ）、室旁核（ＮＰＶ）或ＮＰＶ的投射区：延髓头端腹外侧区（ＲＶＬＭ）、导水管周围灰质（ＰＡＧ）、蓝斑（ＬＣ）内注入血管紧张素Ⅱ（ＡⅡ）均引起升压反应;（２）ＳＦＯ升压反应可被双侧ＮＰＶ或ＲＶＬＭ内预先注入［Ｓａｒ１,Ｔｈｒ８］ＡⅡ（ＳＴＡⅡ,ＡⅡ拮抗剂）明显衰减,ＮＰＶ升压反应也可被ＲＶＬＭ内注入ＳＴＡⅡ削弱;（３）双侧ＰＡＧ用ＳＴＡⅡ预处理后,ＡⅡ引起的ＮＰＶ或ＳＦＯ升压反应均明显减小;（４）ＮＰＶ升压反应还可被双侧ＬＣ内预先注射ＳＴＡⅡ衰减,但ＳＦＯ升压反应不受影响。结合我们以往工作曾显示兴奋ＰＡＧ或ＬＣ均可作用于ＲＶＬＭ引起升压反应,目前的结果表明：ＳＦＯ内的ＡⅡ能神经元通过ＮＰＶ内ＡⅡ能神经元,不仅可直接作用于ＲＶＬＭ引起升压反应,而且还可间接通过ＰＡＧ作用于ＲＶＬＭ起升压作用,但ＬＣ不参与ＳＦＯ升压反应。     

猫颈动脉区压力和化学感受性刺激对孤束核自发放电的影响

对27只氯醛糖和氨基甲酸乙酯麻醉的猫观察了选择性激活颈动脉压力和化学感受器对孤束核(NTS)及其附近区域单位放电的影响。共记录到103个对颈动脉压力感受器激活(新福林1—2μg/kg,iv)和/或颈动脉化学感受器激活(尼古丁,5—20μg,注入甲状腺动脉)起反应的单位,其中81个位于NTS,在这些单位中,14个仅对化学感受器激活起反应(10个兴奋和4个抑制),44个以各种组合形式对化学和压力感受性刺激都起反应,23个仅对压力感受器刺激起反应(18个兴奋和5个抑制)。在定位分布上,对两种刺激都起反应的单位主要位于NTS尾部,仅对化学感受性刺激起反应的单位多位于NTS的腹外侧,其它有反应的单位分别位于舌下神经旁区,旁正中网状核和延髓腹侧尾端。这些结果表明,颈动脉区压力和化学感受器活动传入到NTS,并在其中的一些神经元上发生会聚。 在全部有反应的NTS单位中,68个对压力感受性刺激起反应,其中46个兴奋,21个抑制(P<0.005);58个对化学感受性刺激起反应,其中36个兴奋,22个抑制(P>0.05)。这些结果提示,化学感受性刺激对NTS神经元引起兴奋和抑制两种反应,而压力感受性刺激则诱发兴奋为主的反应。     

孤束核内微电泳NPY对压力感受性和化学感受性激活神经元…

本实验观察了孤束核（ＮＴＳ）内微电泳神经肽Ｙ（ＮＰＹ）对压力感觉性化学感受性刺激反应神经元放电的影响。在６２个单位放电中,其中对微电泳ＮＰＹ表现兴奋反应３４个单位,１９个单位表现抑制反应,无反应单位９个。微电泳ＮＰＹ对压力感受性刺激呈兴奋反应的单位主要表现兴奋作用,对抑制反应单位主要表现抑制作用,对化学感受性刺激的兴奋单位和抑制单位均主要以兴奋为主。     

血管紧张素Ⅱ、心房钠尿肽和血管升压素对大鼠脑片穹窿下器神经元活动的影响

在31个脑片观察了血管紧张素Ⅱ(AGⅡ)、心房钠尿肽(ANP)和血管升压素(AVP)三种多肽对87个穹窿下器(SFO)神经元单位电活动的影响。脑片灌流AGⅡ(10~(-7)mol/L,3min)后,40/55个单应(72.73％)放电频率明显增加,3/55个单位(5.45％)放电频率降低,12/55个单位(21.82％)无明显反应。AGⅡ对SFO放电单位的兴奋作用可被AGⅡ受体阻断剂saralasin(10~(-6)mol/L)完全阻断。脑片灌流心房肽Ⅲ(APⅢ)(10~(-7)mol/L,3min)后,7/17个单位(41.18％)放电频率明显降低,2/17个单位(11.76％)放电频率增加,8/17个单位(47.06％)无明显反应。脑片灌流AVP(10~(-7)mol/L,3min)后,8/15个单位(53.33％)放电频率明显增加,3/15个单位(20.00％)放电频率降低,4/15个单位(26.67％)无明显反应。在观察这三种多肽对同一SFO神经元的作用时,1个单位对AGⅡ和AVP均产生兴奋反应;3个单位对AGⅡ呈兴奋和被APⅢ所抑制;1个单位对AVP呈兴奋,而对APⅢ为抑制,未见到既对AGⅡ和AVP呈兴奋,又为APⅢ所抑制的单位。结果提示:AGⅡ,ANP和AVP三种多肽都能影响SFO神经元的自发电活动,SFO可能也是三者调节机体水盐平衡和血压的中枢部位之一。     

兔孤束核腹外侧区微量注射谷氨酸钠及甘氨酸对膈神经放电的影响

实验在４０只麻醉、制动、断双侧颈迷走神经和人工通气的家兔上进行。在孤束核腹外侧区微量注射神经元胞体兴奋剂谷氨酸钠和抑制剂甘氨酸,探讨膈神经放电的变化。结果：微量注射谷氨酸钠,可使膈神经放电脉冲数明显增加,吸气时程延长,呼气时程缩短,呼吸频率变化不明显;微量注射甘氨酸,则膈神经放电脉冲数显著减少,甚至停止,吸气时程缩短,呼气时程不规则延长,呼吸频率降低。上述结果提示：孤束核腹外侧区对呼吸节律的形成具     

猕猴前额皮层神经元对信号刺激和无关刺激反应的比较研究

在两只已建立视觉分辨行为以及一只未经训练的猕猴上记录了前额皮层主沟区的单位放电,视觉分辨作业包括下列事件;（1）暗示信号红光（在R模式中）或蓝光（在B模式中）（1.30^s);(2）延缓期（2.10s);（3）反应期出现白光（1.88s)在R模式中动物必需在白光出现后立即拉杆以避免电击在B模式中不给予电击,要求动物不拉杆,共记录了127个前额皮层单位,其中80个单位的放电变化与视觉分辨作业的事件相关,占总数的63%,在测试间歇期内观察了前额皮尾神经元对无关的短声\闪光以及闪烁的红、蓝和白光的反应,总共对96个单位进行了短声和/或闪光刺激的测试,其中23个（24%）对上述刺激产生反应,并大部分（15个）是与行为作业中事件相关的单位,在对103个单位进行闪烁的红、蓝、白光测试中,发现只有12个（12%）单位有反应,在另一只未经训练的猕猴的前额皮层主沟区记录了100个单位,发现只有4个（4%）单位对无关的光刺激有反应,这些光刺激的物理性与上述实验中所采用的刺激相同,以上结果表明,通过学习具有行为意义的刺激能引起更多的前额叶神经元的放电活动,也就是说前额叶神经元对具有行为意义的刺激的反应是在学习过程中形成的,它们的活动是可塑的。     

刺激兔面神经核背内侧区对孤束核腹外侧亚核呼吸相关神经元的影响

本工作在氨基甲酸乙酯麻醉、断双侧颈迷走神经、肌松、人工呼吸的家兔上,观察了长短串电脉冲刺激面神经核背内侧区(DMNF)对孤束核腹外侧亚核(VLNTS)呼吸相关神经元(RRU)的影响。实验结果:当电刺激 DMNF 时,吸气性神经元(64.4%)放电频率增加,放电时程延长,并以递增性吸气神经元被兴奋的数量最多。呼气性神经元(35%)表现为放电停止和放电频率减少,以递减性呼气神经元被抑制的数量最多。左右两侧 VLNTS 呼吸相关神经元对电刺激 DMNF 的反应无显著性差异,P>0.05。结果提示:DMNF 兴奋可以易化 VLNTS 吸气性神经元,抑制呼气性神经元。两者之间的功能及结构联系是一个值得注意的问题。     

Integrative responses of neurons in nucleus tractus solitarius to visceral afferent stimulation and vestibular stimulation in vertical planes

Anatomical studies have demonstrated that the vestibular nuclei project to nucleus tractus solitarius (NTS), but little is known about the effects of vestibular inputs on NTS neuronal activity. Furthermore, lesions of NTS abolish vomiting elicited by a variety of different triggering mechanisms, including vestibular stimulation, suggesting that emetic inputs may converge on the same NTS neurons. As such, an emetic stimulus that activates gastrointestinal (GI) receptors could alter the responses of NTS neurons to vestibular inputs. In the present study, we examined in decerebrate cats the responses of NTS neurons to rotations of the body in vertical planes before and after the intragastric administration of the emetic compound copper sulfate. The activity of more than one-third of NTS neurons was modulated by vertical vestibular stimulation, with most of the responsive cells having their firing rate altered by rotations in the head-up or head-down directions. These responses were aligned with head position in space, as opposed to the velocity of head movements. The activity of NTS neurons with baroreceptor, pulmonary, and GI inputs could be modulated by vertical plane rotations. However, injection of copper sulfate into the stomach did not alter the responses to vestibular stimulation of NTS neurons that received GI inputs, suggesting that the stimuli did not have additive effects. These findings show that the detection and processing of visceral inputs by NTS neurons can be altered in accordance with the direction of ongoing movements.     

Reaction of cell population of the rat nucleus tractus solitarius to disorders of carbohydrate metabolism]

Cell responses in disparate subnuclei of the nucleus tractus solitarius (NTS) to experimental alloxan diabetes were studied using light microscopic morphometric methods. Histophysiological features in seven of fourteen cell divisions distinguished in the rat NTS, demonstrated their dependence on impaired carbohydrate metabolism. The data obtained are consistent with the hypothesis of the NTS involvement in the control of carbohydrate homeostasis.     

Neuropeptide-Y stimulation of insulin secretion is mediated via the nucleus tractus solitarius.

Neuropeptide-Y (NPY) is widely distributed in nervous tissue. In the central nervous system, NPY has been shown to be densely located in specific brain regions wherein it may mediate specific functions. Previous data have indicated that NPY may act at a selective site in the brain to modulate insulin secretion. In this study, we investigated the effect of NPY on NTS-mediated insulin secretion. A limited occipital craniotomy was performed on anesthetized rats to expose the caudal medulla in the region of the obex. NPY was microinjected into the NTS and blood samples were subsequently collected from the femoral vein. NPY microinjection resulted in a significant increase in insulin secretion within 5 minutes that returned to baseline at 30 minutes. However, microinjections of NPY did not significantly alter the plasma glucose in this model system. We conclude that NPY can act directly on the NTS to increase circulating insulin levels. Thus, the NTS may be a major brainstem site that directly mediates the central action of NPY on nutrient homeostasis.     

Muscarinic modulation of GABAergic transmission to neurons in the rat subfornical organ

Cholinergic actions on subfornical organ (SFO) neurons in rat slice preparations were studied by using whole cell voltage- and current-clamp recordings. In the voltage-clamp recordings, carbachol and muscarine decreased the frequency of GABAergic inhibitory postsynaptic currents (IPSCs) in a dose-dependent manner, with no effect on the amplitudes or the time constants of miniature IPSCs. Meanwhile, carbachol did not influence the amplitude of the outward currents induced by GABA. Furthermore, carbachol and muscarine also elicited inward currents in a TTX-containing solution. From the current-voltage relationship, the reversal potential was estimated to be -7.1 mV. These carbachol-induced responses were antagonized by atropine. In the current-clamp recordings, carbachol depolarized the membrane with increased frequency of action potentials. These observations suggest that acetylcholine suppresses GABA release through muscarinic receptors located on the presynaptic terminals. Acetylcholine also directly affects the postsynaptic membrane through muscarinic receptors, by opening nonselective cation channels. A combination of these presynaptic and postsynaptic actions may enhance activation of SFO neurons by acetylcholine.     

Responses of neurons in the rat nucleus submedius to noxious and innocuous mechanical cutaneous stimulation

Extracellular recordings were used to characterize responses to cutaneous mechanical stimulation of 78 neurons in the rat nucleus submedius (SM). Thirty-nine of these units were activated by some type of cutaneous mechanical stimulation. Eighteen cells were activated exclusively by noxious stimuli. In 13 of these cells, responses were of swift onset and relatively rapid termination following stimulus application. In contrast, in three neurons responses were delayed both in onset and termination, and in two the response was immediate, but the markedly increased evoked activity outlasted stimulus application by 13 min. Receptive fields (RFs) of these nociceptive neurons were generally large, although none were bilateral. Four SM neurons were activated by innocuous stimuli, but their maximal response was obtained only after noxious stimulation. Responses of all of these neurons were of immediate onset and recovery, and their RFs were large (two were bilateral). Twelve SM neurons were activated maximally by innocuous stimuli. Responses of seven of these cells were immediate in onset and termination, while that of three were delayed in both onset and termination. Two of the 12 innocuous-only neurons quickly became unresponsive to repeated stimulus applications, and could be reactivated only after a rest period during which no stimuli were applied. RFs of these units were also generally large, and in three cases were bilateral. Five SM neurons responded by decreasing, or completely ceasing, their firing subsequent to noxious-only (n = 2), or innocuous-only (n = 3) stimulation. Four of these units had large RFs (two were bilateral). The remaining 39 SM neurons could not be activated by any type of mechanical cutaneous stimulation we tried. Electrical stimulation of the ventrolateral orbital cortex (VLO) was employed to examine frontal cortical projections of 21 SM neurons. Ten of these units were activated, although all of them synaptically rather than antidromically, and two were inhibited. There was no clear-cut relationship between neuronal location, physiological type, RF site, or VLO stimulation effects among the 39 SM neurons. These results provide further support for the involvement of SM neurons in nociceptive information signaling, and suggest additionally that the role of the nucleus is not limited to nociception but encompasses a wider range of cutaneous sensations.     

Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning

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Barosensitive neurons in the rat tractus solitarius and paratrigeminal nucleus: a new model for medullary, cardiovascular reflex regulation

The nucleus of the solitary tract (NTS), a termination site for primary afferent fibers from baroreceptors and other peripheral cardiovascular receptors, contains blood pressure-sensitive neurons, some of which have rhythmic activity locked to the cardiac cycle, making them key components of the central pathway for cardiovascular regulation. The paratrigeminal nucleus (Pa5), a small collection of medullary neurons in the dorsal lateral spinal trigeminal tract, like the NTS, receives primary somatosensory inputs of glossopharyngeal, vagal, and other nerves. Recent studies show that the Pa5 has efferent connections to the rostroventrolateral reticular nucleus (RVL), NTS, and ambiguous nucleus, suggesting that its structure may play a role in the baroreceptor reflex modulation. In the present study, simultaneous recording from multiple single neurons in freely behaving rats challenged with i.v. phenylephrine administration, showed that 83% of NTS units and 72% of Pa5 units were baroreceptor sensitive. Whereas most of the baroreceptor-sensitive NTS and Pa5 neurons (86 and 61%, respectively) increased firing rate during the ascending phase of the pressor response, about 16% of Pa5 and NTS baroreceptor-sensitive neurons had a decreased firing rate. On one hand, the decrease in firing rate occurred during the ascending phase of the pressor response, indicating sensitivity to rapid changes in arterial pressure. On the other hand, the increases in neuron activity in the Pa5 or NTS occurred during the entire pressor response to phenylephrine. Cross-correlational analysis showed that 71% of Pa5 and 93% of NTS baroreceptor-activated neurons possessed phasic discharge patterns locked to the cardiac cycle. These findings suggest that the Pa5, like the NTS, acts as a terminal for primary afferents in the medullary-baroreflex or cardiorespiratory-reflex pathways.     

Secretin depolarizes nucleus tractus solitarius neurons through activation of a nonselective cationic conductance

The recent suggestion that secretin may be useful in treating autism and schizophrenia has begun to focus attention on the mechanisms underlying this gut-brain peptide's actions in the central nervous system (CNS). In vitro autoradiographic localization of (125)I-secretin binding sites in rat brain shows the highest binding density in the nucleus tractus solitarius (NTS). Recent evidence suggests that intravenous infusion of secretin causes fos activation in NTS, a relay station playing important roles in the central regulation of autonomic functions. In this study, whole cell patch-clamp recordings were obtained from 127 NTS neurons in rat medullary slices. The mean resting membrane potential of these neurons was -54.7 +/- 0.3 mV, the mean input resistance was 3.7 +/- 0.2 GOmega, and the action potential amplitude of these neurons was always >70 mV. Current-clamp studies showed that bath application of secretin depolarized the majority (80.8%; 42/52) of NTS neurons tested, whereas the remaining cells were either unaffected (17.3%; 9/52) or hyperpolarized (1.9%; 1/52). These depolarizing effects were maintained in the presence of 5 microM TTX and found to be concentration dependent from 10(-12) to 10(-7) M. Using voltage-clamp techniques, we also identified modulatory actions of secretin on specific ion channels. Our results demonstrate that while secretin is without effect on net whole cell potassium currents, it activates a nonselective cationic conductance (NSCC). These results show that NTS neurons are activated by secretin as a consequence of activation of a NSCC and support the emerging view that secretin can act as a neuropeptide within the CNS.     

Neuroplasticity in nucleus tractus solitarius neurons after episodic ozone exposure in infant primates.

Acute ozone exposure evokes adverse respiratory responses, particularly in children. With repeated ozone exposures, however, despite the persistent lung inflammation and increased sensory nerve excitability, the central nervous system reflex responses, i.e., rapid shallow breathing and decreased lung function, adapt, suggesting changes in central nervous system signaling. We determined whether repeated ozone exposures altered the behavior of nucleus tractus solitarius (NTS) neurons where reflex respiratory motor outputs are first coordinated. Whole cell recordings were performed on NTS neurons in brain stem slices from infant monkeys exposed to filtered air or ozone (0.5 ppm, 8 h/day for 5 days every 14 days for 11 episodes). Although episodic ozone exposure depolarized the membrane potential, increased the membrane resistance, and increased neuronal spiking responses to depolarizing current injections (P < 0.05), it decreased the excitability to vagal sensory fiber activation (P < 0.05), suggesting a diminished responsiveness to sensory transmission, despite overall increases in excitability. Substance P, implicated in lung and NTS signaling, contributed to the increased responsiveness to current injections but not to the diminished sensory transmission. The finding that NTS neurons undergo plasticity with repeated ozone exposures may help to explain the adaptation of the respiratory motor responses.