Subfornical organ and hypothalamic paraventricular nucleus connections with median preoptic nucleus neurons: an electrophysiological study in the rat

Summary The role of pathways from the subfornical organ (SFO) to the hypothalamic paraventricular nucleus (PVN) through the median preoptic nucleus (MnPO) in regulating the activity of putative vasopressin (VP)-secreting neurons in the PVN was examined in urethane-anesthetized male rats. The activity of the majority (79%) of SFO neurons antidromically identified as projecting to the MnPO was excited by microiontophoretically (MIPh) applied angiotensin II (ANG II) and the effect was blocked by MIPh-applied saralasin (Sar), an ANG II antagonist. Identified SFO neurons that were excited by MIPh-applied ANG II were also excited by intravenously administered ANG II. Electrical stimulation of the SFO produced orthodromic excitation (48%) or inhibition (24%) of the activity of MnPO neurons antidromically identified as projecting to the PVN. Identified MnPO neurons that were excited by SFO stimulation were also excited by MIPh-applied ANG II, while the remaining neurons were not affected. The excitatory responses to SFO stimulation and to MIPh-applied ANG II were both blocked by MIPh-applied Sar, whereas the inhibitory responses to SFO stimulation were not affected. ANG II injected into the region of the SFO produced either an excitation (55%) or no effect (45%) on the activity of identified MnPO neurons. Electrical stimulation of the MnPO produced orthodromic excitation (27%) or inhibition (23%) of the activity of putative VP-secreting PVN neurons. ANG II injected into the region of the MnPO produced either an excitation (31%) or no effect (69%) on the activity of putative VP-secreting PVN neurons. These observations reveal some possible interconnections between three brain regions and suggest that circulating ANG II excites a population of neurons projecting from the SFO to the MnPO, and that these neurons themselves release ANG II as an excitatory transmitter on part of MnPO neurons projecting to the PVN, thereby causing enhanced activity of putative VP-secreting PVN neurons.     

Involvement of the median preoptic nucleus in the regulation of paraventricular vasopressin neurons by the subfornical organ in the rat

Summary Extracellular recordings in urethane-anesthetized male rats indicated that electrical stimulation of the subfornical organ (SFO) alters the activity of 54 out of 62 phasically firing neurosecretory neurons in the hypothalamic paraventricular nucleus (PVN); 44 cells demonstrate an increase in excitability; 10 cells display a depression in their activity. In 14 out of 38 PVN cells tested, SFO stimulation-evoked excitations were abolished by pretreatment with the angiotensin II (ANG II) antagonist, saralasin (Sar), in the region of the median preoptic nucleus (MnPO). Inhibitory responses (n=7) were not affected. Microinjection of ANG II into the region of the SFO produced either a facilitation (n=28) or no effect (n=6) on the excitability of phasically active PVN neurosecretory cells and the facilitatory effect of 9 out of 23 cells tested was prevented by pretreatment with Sar in the region of the MnPO. All the PVN cells which had excitatory responses to either electrical (n=7) or chemical (n=9) stimulation of the SFO that were blocked following the pretreatment could also be activated by intravenous administration of ANG II. Furthermore, this activation was blocked (n=10) or attenuated (n=6) by pretreatment with Sar in the region of the MnPO. These results show an involvement of both the MnPO and the SFO for the regulation of excitability of putative vasopressin (VP)-secreting PVN neurons, and suggest that MnPO neurons sensitive to ANG II may relay activation of SFO neurons by circulating ANG II to putative VP-secreting PVN neurons which result in enhanced excitability.     

The paraventricular nucleus of hypothalamus mediates the pressor response to noradrenergic stimulation of the medial prefrontal cortex in unanesthetized rats

The medial prefrontal cortex (MPFC) is a structure that is also involved in cardiovascular modulation. The injection of norepinephrine (NE) into the prelimbic (PL) area of the MPFC of unanesthetized rats evokes a pressor response which is mediated by acute vasopressin release. Vasopressin is synthesized by magnocellular cells of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. In the present study, we endeavored to determine which vasopressin-synthesizing hypothalamic nucleus is involved in the pressor pathway activated after NE injection into the PL area of the MPFC. We report here that lidocaine microinjection into the SON did not change the pressor response evoked by NE injection into the PL. However, the response to NE was blocked by prior injection of lidocaine or CoCl₂ into the PVN, indicating that this area is responsible for the mediation of this pressor response. A neuroanatomic experiment in which the neuronal tracer biotinylated dextran amine (BDA) was microinjected into the MPFC showed a lack of axons or neuronal cell bodies in the PVN, indicating that there are no direct connections between the PL area of the MPFC and the PVN. The results suggest that the PVN is involved in the mediation of the pressor response to NE in the PL area and that this pathway must relay in other brain structures before reaching the PVN.     

腹腔注射2-脱氧-D-葡萄糖可诱发大鼠视上核和室旁核神经元表达Fos

目的 探讨腹腔注射2-脱氧-D-葡萄糖（2-DG）能否激活大鼠下丘脑视上核（SON）和室旁核（PVN）神经元而表达Fos。方法 健康雄性SD大鼠12只,随机分为腹腔注射2-DG组（6只）、生理盐水对照组（3只）及正常对照组（3只）。各自处理后,应用免疫组织化学方法,观察各组下丘脑SON和PVN内Fos表达及其与催产素（OT）和加压素（VP）的双标情况,同时采用ELISA方法对血清中OT和VP的含量进行检测。 结果与生理盐水对照组和正常对照组相比,2-DG引发的特异性Fos免疫阳性产物主要集中分布于下丘脑外侧区和穹隆周区,在SON、PVN也有密集表达。SON和PVN内的Fos表达与该区的特异性神经活性物质OT和VP有共存。OT/Fos双标细胞率（双标细胞占OT阳性细胞的百分率）在SON和PVN分别为87.10%、90.57%,明显高于VP/Fos在这两个核团的双标率（双标细胞占VP阳性细胞的百分率,68.42%、76.92%）,两者比较差异有统计学意义（P<0.05）。ELISA检测结果显示,2-DG组动物血清中OT和VP水平与对照组相比无明显变化。 结论 腹腔注射2-DG可激活大鼠下丘脑SON和PVN内OT和VP神经元表达Fos,SON和PVN可能参与2-DG诱导的急性应激反应。     

Efferent pathways from the region of the subfornical organ to hypothalamic paraventricular nucleus: an electrophysiological study in the rat

Summary Twenty-three neurons in the region of the subfornical organ (SFO) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) in male rats under urethane anesthesia. Microiontophoretically (MIPh) applied angiotensin II (AII) excited the activity of all units in the region of the SFO and the effect of AII was blocked by MIPh applied saralasin (Sar), an AII antagonist, but not by atropine (Atr), a muscarinic antagonist. In these units, 12 were also excited by MIPh applied acetylcholine (ACh) while 11 were not affected and the effect of ACh was attenuated by not only MIPh applied Atr, but also Sar, suggesting that not only neurons specific for AII, but also neurons sensitive to both AII and ACh project to the PVN in the region of the SFO. Intravenously administered AII excited the activity of both types of units in the region of the SFO. Microinjected AII or ACh into the region of the SFO excited the activity of putative vasopressin (VP)-secreting units in the PVN. These results suggest that neurons projecting to the PVN in the region of the SFO may act to enhance the activity of putative VP-secreting neurons in the PVN in response to circulating AII.     

Gastric afferents to the paraventricular nucleus in the rat

Summary Extracellular recordings were made from vasopressin (AVP) and oxytocin (OXT)-secreting cells in the paraventricular nucleus (PVN) of the hypothalamus in rats anesthetized with urethane-chloralose to determine the effects of electrical stimulation of vagal gastric nerves and gastric distension on their activity. Electrical stimulation of gastric branches of the vagus nerves inhibited 5 and excited 10 of 32 phasically firing neurosecretory cells. Approximately one third of the phasically firing neuro-secretory cells (9 out of 29 cells) were transiently inhibited by gastric distension; an effect which was completely abolished by bilateral cervical vagotomy. In contrast, gastric nerve stimulation excited 45 of 72 non-phasically firing paraventricular cells. Thirteen of 77 non-phasically firing cells tested were excited by gastric distension. We conclude that there are some sensory afferent inputs originating from gastric receptors and transmitted by gastric vagal afferents which inhibit the activity of AVP- secreting neurons in the PVN although other inputs excite the cells. Similar inputs also excite some of the putative OXT-secreting neurons in the PVN.     

An investigation of a possible direct projection from the medial nucleus of the cerebellum to the paraventricular nucleus of the hypothalamus in the rat: a study using retrograde WGA-HRP and Fluoro-Gold tracing techniques

Retrograde transport of lectin-conjugated horseradish peroxidase and Fluoro-Gold was used in an attempt to obtain data to confirm the existence, predicted from physiological studies, of a direct, monosynaptic projection from the medial nucleus of the cerebellum (MN) to the paraventricular nucleus of the hypothalamus (PVH) in the rat. Injections of these two tracers that included the PVH and surrounding diencephalic structures, or that in the case of Fluoro-Gold were localized to the PVH, resulted in retrograde neuronal labeling in widely separated nuclei known to project to the areas included in the injection sites. Thus, effective uptake and transport of both tracers occurred under the experimental conditions employed in this study. However, injections confined to the PVH and regions of the hypothalamus adjacent to it, or to the PVH alone, produced no retrograde neuronal labeling in the medial nucleus, indicating that the MN does not project directly to the PVH. Alternative explanations for the findings from physiological experiments were sought. The possibility that electrical stimulation of fibers of passage through the region of the MN might produce a monosynaptic response in the contralateral PVH was discarded, because retrogradely labeled neurons in nuclei such as the locus ceruleus and lateral parabrachial nucleus were distributed mainly ipsilateral to hypothalamic injection sites. However, tracer injections into the MN produced retrograde labeling of neurons in the same region of the lateral paragigantocellular nucleus (LPGi) in which labeled cells were found following tracer injections into the PVH. Axon collaterals of individual neurons in the LPGi might, therefore, project both to the MN and to the PVH. The possibility that such a circuit could, in the absence of a direct MN to PVH projection, provide the basis to explain the physiological findings is discussed.Abbreviations CVL Caudal ventrolateral medulla - DAO dorsal accessory olive - F fornix - FDP fastigial depressor response - FG Fluoro-Gold - FPR fastigial pressor response - LC locus ceruleus - LHA lateral hypothalamic area - LPB lateral parabrachial nucleus - LPGi lateral paragigantocellular nucleus - LRN lateral reticular nucleus - MAO medial accessory olive - MN medial nucleus of the cerebellum - NTS nucleus of the tractus solitarius - PVH paraventricular nucleus of the hypothalamus - RVL rostral ventrolateral medulla - SCP superior cerebellar peduncle - SFO subfornical organ - V ₃ third ventricle - V ₄ fourth ventricle - WGA-HRP wheat germ agglutinin-conjugated horseradish peroxidase     

大鼠下丘脑室旁核对淋巴结免疫功能的神经调控

目的探讨下丘脑室旁核(PVH)是否通过直接的神经联系对淋巴结的功能进行调控。方法采用假狂犬病毒(PRV)跨神经元追踪方法研究肠系膜淋巴结注射PRV大鼠PVH内PRV感染神经元的分布，同时采用免疫组化方法研究腹腔注射细菌脂多糖(LPS)后大鼠PVH c-fos表达的变化。结果在注射PRV动物的PVH内出现被PRV标记的阳性神经元，既有大细胞神经元，也有小细胞神经元，它们主要分布在PVH尾侧帽部和内侧部。。FOS阳性产物在PVH的神经元核中出现，其阳性细胞的分布范围及阳性细胞的数目在LPS注射组均明显大于对照组。两批不同实验动物的相同冠状平面比较，可发现PVH中大多数PRV标记的阳性神经元出现在LPS注射后FOS阳性细胞数目增多的区域内。结论PVH可能通过直接的神经环路与淋巴结相互联系，且通过此联系对淋巴结的免疫功能进行调控。     

The effects of paraventricular hypothalamic lesions on maternal behavior in rats

The present study was undertaken to determine whether the disruptive effects of knife cuts which sever the lateral connections of the medial preoptic area (MPOA) on maternal behavior are mediated by interfering with the output of the paraventricular hypothalamic nucleus (PVN). Postpartum rats received one of the following: Knife cuts severing the lateral connections of the MPOA; knife cuts severing the lateral connections of the PVN; radiofrequency lesions of the PVN; sham lesions or knife cuts. Only females that received knife cuts severing the lateral connections of the MPOA showed severe deficits in maternal behavior. These results indicate that the influence of the MPOA on maternal behavior is not mediated by the output of the PVN. Since the PVN is the major source of oxytocin input to other brain regions, these results also suggest that oxytocinergic neural pathways are not critical for postpartum maternal behavior. Another important finding was that females with MPOA knife cuts that did not retrieve their young were capable of hoarding candy, suggesting that the retrieval deficit was not the result of a general oral motor deficit.     

Enkephalin innervation of the paraventricular nucleus of the hypothalamus: distribution of fibers and origins of input

The opioid peptide enkephalin emerges as a major neuromodulator in the regulation and integration of the physiologic response in stressful conditions. The paraventricular nucleus of the hypothalamus is a coordinating center of neuroendocrine and autonomic functions. However, the detailed distribution of the enkephalin fibers and terminals in the paraventricular nucleus and the sources of enkephalinergic innervation are not well defined. In the present study, we used immunocytochemistry for the proenkephalin-derived octapeptide met-arg⁶-gly⁷-leu⁸ enkephalin to determine the distribution of enkephalin-immunoreactive fibers and somata within paraventricular nucleus. Without colchicine pretreatment, enkephalinergic fibers were prominent mainly in the ventromedial part of the parvicellular subdivision of the paraventricular nucleus, appearing in coronal sections as a dense collection of short segments of enkephalin-immunoreactive fibers. In the periventricular portion of the paraventricular nucleus, enkephalin-immunoreactive fibers produced a moderate plexus of short enkephalin-immunoreactive fibers dorsoventrally oriented. With colchicine treatment, a dense cluster of enkephalin-immunoreactive cell bodies was located in the dorsomedial and the dorsal parts of the parvicellular subdivisions. These enkephalin-immunoreactive neurons were small (< 10 μm) to medium sized (10–15 μm), with round and elongated shapes. Retrograde transport of wheat germ-conjugated gold particles. WGA-apoHRP-Au, from the paraventricular nucleus, combined with immunocytochemistry for enkephalin revealed that the major sources of extrahypothalamic enkephalin afferents to the paraventricular nucleus are provided by enkephalin neurons neurons in the lateral reticular nucleus and the paragigantocellularis reticular nucleus of the medulla (20% of retrogradely labeled neurons within this nucleus were double labeled) and in the nucleus solitary tract (10% of retrogradely labeled neurons within thisnucleus were double labeled). Retrogradely labeled enkephalin neurons were also observed in the medial preoptic area, median preoptic nucleus, dorsomedial hypothalamic nucleus, lateral septum and hypothalamic arcuate nucleus. These enkephalinergic pathways from the medulla and the forebrain could represent an anatomical substrate underlying the opioid effects on paraventricular neurons during physiological processes, such as a cardiovascular regulation, feeding or stress responses.     

6-羟多巴损伤黑质导致室旁核离子钙接头蛋白表达变化

目的　观察6-羟多巴（6-hydroxydopamine,6-OHDA）损伤大鼠黑质损伤后下丘脑室旁核（paraventricular nucleus of hypothalamus,PVN）中离子钙接头蛋白1（ionized calcium binding adapter molecule-1,Iba1）的含量变化。 方法　30只SD大鼠根据随机数字表分为6-OHDA大鼠组和对照组各15只。6-OHDA大鼠组双侧黑质内注射6-羟多巴,对照组双侧黑质（substantia nigra,SN）内注射等体积的生理盐水。6周后断头取脑,Nissl染色、免疫组化、免疫印迹方法鉴定成模,免疫组化、免疫印迹和RT-PCR检测室旁核Iba1的表达。 结果　与对照组比较,6-OHDA大鼠组SN内酪氨酸羟化酶（tyrosine hydroxylase, TH）阳性神经细胞数量从（58±5）个减少到（10±2）个（P<0.05）,蛋白表达水平从(0.71±0.12)降低至(0.28±0.12)（P<0.05）,室旁核中Iba1阳性细胞数量从（7±2）个增加到（14±3）个（P<0.05）,蛋白表达水平从(0.1±0.08)增加到(0.19±0.06)（P<0.05）。 结论　6-OHDA大鼠PVN中Iba1的表达变化有可能与帕金森病患者的胃肠功能障碍存在一定的联系。     

Electrophysiological evidence for connections between septal neurones and the supraoptic nucleus of the hypothalamus of the rat

Summary In order to see whether septal neurones are connected to the hypothalamic neurones secreting vasopressin or oxytocin, neurones in different regions of the septum were recorded during electrical stimulation of the supraoptic nucleus. The position of the stimulating electrode within the latter was verified using lactating rats in which milk ejections could be induced by a train of electrical pulses applied to the nucleus. The responses of septal neurones to single pulse stimulation were then analysed by post-stimulus time histograms.In the septum ipsilateral to the site of stimulation, 42% of the neurones were antidromically invaded, 20% were orthodromically excited and 21% were inhibited following supraoptic stimulation. In the contralateral septum, 2% of the cells tested were antidromically invaded, 3% were excited and 16% inhibited. In the medial septum, 14% of the neurones were orthodromically excited, and 48% were inhibited.These results provide electrophysiological evidence for direct connections between septal neurones and the ipsilateral supraoptic nucleus of the hypothalamus, and give further support to the hypothesis of a septal influence on the activity of vasopressin- or oxytocin-releasing cells in the magnocellular system.Supported by grants I.N.S.E.R.M. CRL 79.5.372.6     

Corticotropin-releasing factor projections from limbic forebrain and paraventricular nucleus of the hypothalamus to the region of the ventral tegmental area

Corticotropin-releasing factor (CRF) is a peptide neurotransmitter with high numbers of cell bodies found in limbic regions of the rat brain including the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and central nucleus of the amygdala (CeA) as well as in the paraventricular nucleus of the hypothalamus (PVN). CRF systems are activated in response to acute stressors and mediate a wide variety of physiological and behavioral responses to acute stress including aversive responses and responses that support appetitive behaviors. CRF is released in the ventral tegmental area (VTA), the cell body region of the mesocorticolimbic dopaminergic neurons, in response to acute stress and plays a role in stress-activation of appetitive behavior [Wang B, Shaham Y, Zitzman D, Azari S, Wise RA, You ZB (2005) Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: a role in stress-induced relapse to drug seeking. J Neurosci 25:5389-5396]. However, although it is known that the VTA region contains significant levels of CRF-immunoreactive fibers [Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36:165-186], the source of CRF input to the region has not been identified. We used infusions of a fluorescent retrograde tracer, fluorogold, into the VTA region, combined with fluorescent immunocytochemistry for CRF to identify sources of this input. Double-labeled cells were found in BNSTov, CeA and PVN. The percent of fluorogold-labeled cells in each region that were CRF-positive was 30.8, 28.0 and 16.7% respectively. These data point to diffusely distributed sources of CRF-containing fibers in the VTA.     

The role of oxytocin and the paraventricular nucleus in the sexual behaviour of male mammals

The paraventricular nucleus of the hypothalamus contains the cell bodies of a group of oxytocinergic neurons projecting to extrahypothalamic brain areas and to the spinal cord, which are involved in the control of erectile function and copulation. In male rats, these neurons can be activated by dopamine, excitatory amino acids, nitric oxide (NO), hexarelin analogue peptides and oxytocin itself to induce penile erection and facilitate copulation, while their inhibition by gamma-aminobutyric acid (GABA) and GABA agonists and by opioid peptides and opiate-like drugs inhibits sexual responses. The activation of paraventricular oxytocinergic neurons by dopamine, oxytocin, excitatory amino acids and hexarelin analogue peptides is apparently mediated by the activation of nitric oxide (NO) synthase. NO in turn activates, by a mechanism that is as yet unidentified, the release of oxytocin from oxytocinergic neurons in extrahypothalamic brain areas. Paraventricular oxytocinergic neurons and mechanisms similar to those reported above are also involved in the expression of penile erection in physiological contexts, namely, when penile erection is induced in the male by the presence of an inaccessible receptive female, which is considered a model for psychogenic impotence in man, as well as during copulation. These findings show that paraventricular oxytocinergic neurons projecting to extrahypothalamic brain areas and to the spinal cord and the paraventricular nucleus play an important role in the control of erectile function and male sexual behaviour in mammals.     

Endogenous hydrogen peroxide in paraventricular nucleus mediating cardiac sympathetic afferent reflex and regulating sympathetic activity

We previously reported that reactive oxygen species (ROS) in paraventricular nucleus (PVN) mediated cardiac sympathetic afferent reflex (CSAR). The present study investigated the role of endogenous hydrogen peroxide (H₂O₂), a ROS, in the PVN in mediating the CSAR and regulating sympathetic activity. The CSAR was evaluated by the response of renal sympathetic nerve activity (RSNA) to epicardial application of bradykinin (BK) in rats. Bilateral microinjection of polyethylene glycol-catalase (PEG-CAT, an analogue of endogenous catalase) or polyethylene glycol-superoxide dismutase (PEG-SOD, an analogue of endogenous superoxide dismutase) into the PVN abolished the CSAR, decreased baseline RSNA and mean arterial pressure (MAP). Moreover, pretreatment with PEG-CAT or PEG-SOD blocked the enhanced CSAR and RSNA responses induced by exogenous angiotensin II (Ang II) in the PVN. Aminotriazole (ATZ, a catalase inhibitor) alone potentiated the CSAR, increased RSNA and MAP, but failed to augment the Ang II-induced CSAR enhancement responses. Pretreated with PEG-SOD, ATZ still increased baseline RSNA and MAP but inhibited the CSAR and Ang II-induced CSAR and RSNA enhancement responses. These results suggested that endogenous H₂O₂ in the PVN mediated both the CSAR and Ang II-induced CSAR enhancement responses. H₂O₂ in the PVN were involved in regulating sympathetic activity and arterial pressure.     

脑室注射组胺对下丘脑室旁核促皮质素释放激素神经元的作用

目的:观察第三脑室注射组胺对下丘脑室旁核促皮质素释放激素(CRH)神经元活动的影响。方法:Fos癌蛋白免疫组化LSAB法结合双抗原标记法;半定量逆转录聚合酶链反应(RT-PCR)方法。结果:第三脑室注射组胺后,(1)下丘脑室旁核Fos阳性神经元数目明显增加(P＜0.05);(2)室旁核内的Fos阳性神经元中约有31.78%同时呈CRH阳性反应;(3)室旁核CRHmRNA含量明显升高,且有量效关系。结论:中枢组胺可以激活下丘脑室旁核的CRH神经元,并使CRH基因表达增加。     

Interaction of hypertonic NaCl,hemorrhage and angiotensin II in stimulating paraventricular neurosecretory cells in the rat

Summary Antidromically identified paraventricular neurosecretory cells were recorded extracellularly in urethane-anesthetized female rats. Their activity was examined for response to 0.3 M NaCl (0.1 ml, intracarotid injection) and hemorrhage (10 ml/kg b.w.) applied separately or in combination, and was also investigated for the interaction of these stimuli with angiotensin II (AII). About half (51%) of the 106 neurosecretory cells recorded were excited both by osmotic stimuli and by hemorrhage. The remaining cells exhibited various combinations of responses such as no change after 0.3 M NaCl and excitation after hemorrhage (24.5%), no change after either stimulus (19.8%), no change after 0.3 M NaCl and inhibition after hemorrhage (3.8%), and excitation after 0.3 M NaCl and no change after hemorrhage (0.9%). When the neurosecretory cells which did not respond to the 0.3 M NaCl were tested for response to the combined application of 0.3 M NaCl and subthreshold bleeding stimulus (2.5–5.0 ml/kg b.w.), 65.4% of them (n = 26) showed an excitatory response. A subthreshold dose (5 ng) of AII injected into the third ventricle (IVT) potentiated the response to 0.3 M NaCl in 61.8% of the neurosecretory cells (n = 34), whereas the same dose of AII had no effect on the response to hemorrhage (10 ml/kg b.w.). An AII antagonist, saralasin (1 g, IVT), inhibited a response to 0.3 M NaCl in 80.8% of the neurosecretory cells (n = 26), while it affected a response to hemorrhage (10 ml/kg b.w.) in none of them. However, when the dose of saralasin was increased to 4 or 5 g, it inhibited not only a response to 0.3 M NaCl but also a spontaneous firing activity and a response to hemorrhage of the neurosecretory cells (n = 5). These results suggest that an osmotic stimulus interacts with hemorrhage or AII in stimulating the neurosecretory cell and that endogenous AII is involved in the mechanism for osmotic activation of the neurosecretory cell. On the other hand, hemorrhage seemed hardly to interact with AII, although a dose of saralasin large enough to inhibit the spontaneous activity of neurosecretory cells suppressed their excitatory response to hemorrhage.Supported by Grant-in-Aid for Scientific Research (348 105) from the Ministry of Education, Science and Culture of Japan     

Activation within dorsal medullary nuclei following stimulation in the hypothalamic paraventricular nucleus in rats

The influence of the hypothalamic paraventricular nucleus (PVN) on neurones in the dorsal medulla has been examined in 71 urethane/sagatal-anaesthetised rats. Of 536 neurones localised and tested for responses to electrical stimulation of both the vagus and/or the PVN, 378 were synaptically or antidromically activated following vagal stimulation 72 of which were synaptically activated by stimulation within PVN. The majority of those were located at the border between NTS and dorsal motor nucleus of the vagus in caudal NTS. None showed cardiac or ventilatory rhythm. Neurones showing such rhythms were not affected from PVN. Of 89 neurones in dorsal motor nucleus of the vagus, ten were synaptically activated and two synaptically depressed from PVN. PVN activated neurones in NTS tested for responses to stimulation of arterial baroreceptors and carotid body chemoreceptors were either unaffected or inhibited, but gastric inflation excited them. The results suggest a powerful PVN influence on the dorsal medulla, which is largely confined to the ventral and caudal NTS. There is little evidence for an effect on neurones with a cardiovascular function, but the abdominal vagal influence suggests a link with feeding.     

大鼠视上核、室旁核肠三叶因子表达与实验性胃溃疡的关系

目的探讨大鼠实验性胃溃疡自愈期间肠三叶因子(ITF)在下丘脑视上核(SON)、室旁核(PVN)的表达及其与实验性胃溃疡愈合的关系。方法以免疫组织化学染色、酶联免疫吸附实验分别检测溃疡组(42只)和正常组(6只)大鼠下丘脑和血清及ITF的表达及含量变化,RT-PCR检测ITFmRNA的转录情况。结果 ITF免疫反应阳性物质主要位于视上核和室旁核大细胞部。溃疡1d视上核和室旁核ITF积分吸光度略增高,2d、4d和6d逐渐升高,6d达高峰(P0.01),10～23d均维持在较高水平(P0.05)。血清ITF的变化与免疫组织化学法结果相似;溃疡组ITF/3-磷酸甘油醛脱氢酶(GAPDH)吸光度比值在溃疡2～23d均高于正常组(P0.01,或P0.05)。结论胃溃疡自愈期间可能通过下丘脑和血清ITF的高表达参与溃疡愈合的调节。