Refractory hypertension often involves centrally driven sympathetic augmentation. Yet effective central targets for the treatment of hypertension are still scarce. Here, the role of the histamine H4 receptor (H4R) is explored, the newest member of the histamine receptor family, in central cardiovascular regulation. Analysis of single-nucleus RNA-sequencing datasets of human brains and RNAscope assays of rat brains reveal a conservative expression of H4R in the rostral ventromedial medulla (RVMM), a key sympathetic cardiovascular center. Optoactivation of RVMM histaminergic afferents evokes depressor and bradycardic responses via H4R, whose activation excites GABAergic presympathetic neurons by transient receptor potential vanilloid 1 (TRPV1). Intranasal delivery of H4R agonist produces sustained blood pressure-lowering effects in free-moving spontaneously hypertensive rats and stress-induced hypertensive rats. The findings reveal an antihypertensive role of RVMM histamine H4R and a potential central therapeutic target for hypertension.

INTRODUCTION Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4％of the total disease burden.1 Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.

The cerebellum is the largest subcortical motor structure, mainly responsible for motor coordination and control. Cerebellar damage and dysfunction caused by hereditary or endogenous/exogenous factors will lead to cerebellar ataxia. Patients with cerebellar ataxia suffer from balance and gait dysfunction, limb movement deficits, oculomotor abnormalities, as well as dysarthria, which seriously affect their quality of life and constitute a heavy social and economic burden. However, the diverse pathogenesis poses great challenges in the prevention and treatment of cerebellar ataxia. Here we review the current knowledge of the etiology, symptoms, and clinical classification of cerebellar ataxia. The latest research progress on the neural mechanism of cerebellar ataxia has been summarized, in particular, from the view of the structure and dysfunction of neurons, neural circuits, and glial cells in the cerebellum. Furthermore, based on the current clinical treatment of cerebellar ataxia, we also propose and discuss the advantages and disadvantages of new strategies of targeting the neurotransmitter system of cerebellar circuitries, microglia-mediated neuroinflammation, virulence genes of hereditary cerebellar ataxia, as well as brain stimulation intervention during the treatment of cerebellar ataxia. This review may provide a useful reference for the development of more effective therapies for cerebellar ataxia in the future.

The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.

Betahistine and gastrodin are the first-line medications for vestibular disorders in clinical practice, nevertheless, their amelioration effects on vestibular dysfunctions still lack direct comparison and their unexpected extra-vestibular effects remain elusive. Recent clinical studies have indicated that both of them may have effects on the gastrointestinal (GI) tract. Therefore, we purposed to systematically compare both vestibular and GI effects induced by betahistine and gastrodin and tried to elucidate the mechanisms underlying their GI effects. Our results showed that betahistine and gastrodin indeed had similar therapeutic effects on vestibular-associated motor dysfunction induced by unilateral labyrinthectomy. However, betahistine reduced total GI motility with gastric hypomotility and colonic hypermotility, whereas gastrodin did not influence total GI motility with only slight colonic hypermotility. In addition, betahistine, at normal dosages, induced a slight injury of gastric mucosa. These GI effects may be due to the different effects of betahistine and gastrodin on substance P and vasoactive intestinal peptide secretion in stomach and/or colon, and agonistic/anatgonistic effects of betahistine on histamine H1 and H3 receptors expressed in GI mucosal cells and H3 receptors distributed on nerves within the myenteric and submucosal plexuses. Furthermore, treatment of betahistine and gastrodin had potential effects on gut microbiota composition, which could lead to changes in host-microbiota homeostasis in turn. These results demonstrate that gastrodin has a consistent improvement effect on vestibular functions compared with betahistine but less effect on GI functions and gut microbiota, suggesting that gastrodin may be more suitable for vestibular disease patients with GI dysfunction.

Vestibular compensation is an important model for developing the prevention and intervention strategies of vestibular disorders, and investigating the plasticity of the adult central nervous system induced by peripheral injury. Medial vestibular nucleus (MVN) in brainstem is critical center for vestibular compensation. Its neuronal excitability and sensitivity have been implicated in normal function of vestibular system. Previous studies mainly focused on the changes in neuronal excitability of the MVN in lesional side of the rat model of vestibular compensation following the unilateral labyrinthectomy (UL). However, the plasticity of sensitivity of bilateral MVN neurons dynamically responding to input stimuli is still largely unknown. In the present study, by using qPCR, whole-cell patch clamp recording in acute brain slices and behavioral techniques, we observed that 6 h after UL, rats showed a significant deficit in spontaneous locomotion, and a decrease in excitability of type B neurons in the ipsilesional rather than contralesional MVN. By contrast, type B neurons in the contralesional rather than ipsilesional MVN exhibited an increase in response sensitivity to the ramp and step input current stimuli. One week after UL, both the neuronal excitability of the ipsilesional MVN and the neuronal sensitivity of the contralesional MVN recovered to the baseline, accompanied by a compensation of spontaneous locomotion. In addition, the data showed that the small conductance Ca2+-activated K+ (SK) channel involved in the regulation of type B MVN neuronal sensitivity, showed a selective decrease in expression in the contralesional MVN 6 h after UL, and returned to normal level 1 week later. Pharmacological blockage of SK channel in contralateral MVN to inhibit the UL-induced functional plasticity of SK channel significantly delayed the compensation of vestibular motor dysfunction. These results suggest that the changes in plasticity of the ipsilesional MVN neuronal excitability, together with changes in the contralesional MVN neuronal sensitivity, may both contribute to the development of vestibular symptoms as well as vestibular compensation, and SK channel may be an essential ionic mechanism responsible for the dynamic changes of MVN neuronal sensitivity during vestibular compensation.

Coenzymes are required in the reaction catalyzed by oxidoreductases. The research on coenzyme regeneration has always been a hot topic in the field of biological catalysis. In this work, we tried to construct a coimmobilization system of glucose dehydrogenase (GDH), (R)-1-phenylethanol dehydrogenase ((R)-PEDH) and coenzyme with functional magnetic nanoparticles as carriers, so as to realize chiral (R)-1-phenylethanol highly selective production and coenzyme effective recycling. The enzymatic properties of immobilized enzymes were explored. The results showed that the immobilized enzymes had improved stability and fine reusability. In addition, during the catalytic coupling reaction at a final concentration of 2.63 mu M NAD+, the total turnover number (TTN) was as high as 924, and the volumetric productivity of (R)-1-phenylethanol was 37.06 mg.L-1.h(-1). After reused for 10 cycles, the catalytic efficiency of immobilized coenzyme can still be maintained at more than 30%. From multiple perspectives, the immobilized dual-enzymes and coenzyme system seems to be a multifunctional system for (R)-1-phenylethanol production and coenzyme regeneration.

目的:探讨大蒜素(ALL)对血管性痴呆(VD)大鼠学习记忆能力的影响及其可能的作用机制.方法:采用改良双侧颈总动脉阻断法制备VD大鼠模型,造模成功后随机分为VD组,ALL低剂量组(ALL-L组)和ALL高剂量组(ALL-H组),对假手术组(S组)大鼠进行假手术,每组15只;ALL-L组和ALL-H组造模后分别股静脉注射ALL 5,20 mg· kg-1,S组和VD组注射同体积生理盐水,每天1次,连续2周.治疗完成后用Morris水迷宫实验检测大鼠的学习记忆能力;苏木素-伊红(HE)染色观察海马区脑组织病理特点;检测大鼠脑组织中炎症因子肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6),IL-lβ的水平和氧化应激反应指标丙二醛(MDA),超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)的含量;末端脱氧核苷酸转移酶介导dUTP缺口末端标记(TUNEL)法检测海马区细胞的凋亡率;蛋白免疫印迹法(Western blot)检测脑组织中凋亡及自噬相关蛋白半胱氨酸天冬氨酸蛋白水解酶-3 (Caspase-3),B淋巴细胞瘤-2(Bcl-2),Bcl-2相关X蛋白(Bax),微管相关蛋白l轻链3(LC3)Ⅱ,LC3Ⅰ及自噬关键分子酵母Atg6同系物(Beclin-1)的表达.结果:与VD组比较,ALL-H组及ALL-L组大鼠的学习记忆能力明显优于VD组(P＜0.05),海马组织中TNF-α,IL-6,IL-1β水平及MDA含量明显低于VD组(P＜0.05),SOD及GSH-Px的活力明显高于VD组(P＜0.05),细胞凋亡率明显低于VD组(P＜0.05),且ALL-H组较ALL-L组更明显(P＜0.05).ALL-L及ALL-H组海马组织中Caspase-3,Bax,LC3Ⅱ/LC3 Ⅰ及Beclin-1表达水平明显低于VD组(P＜0.05),Bcl-2表达水平明显高于VD组(P＜0.05),且ALL-H组较ALL-L组更明显(P＜0.05).结论:ALL可一定程度上改善VD大鼠的学习记忆能力,其机制可能与对炎症反应、氧化应激、细胞凋亡和自噬的抑制有关.

行为(Behavior),是机体为了维持个体生存和种族延续对外界环境和内在生理变化做出的整体适应性反应,是基因—脑—环境间相互作用和漫长的进化过程中自然选择的结果. 行为可分为先天与生俱来的本能行为和后天学习形成的习得性行为.其中,摄食、攻击、逃跑、睡眠和性等本能性行为,由遗传信息编码的固有神经环路所控制,尽管在不同物种间本能行为的形式各异但却是高度保守的.就像节肢动物和脊索动物这两种不同的物种,早在约5.4亿年前的寒武纪就已经开始分化,但这些不同种类的动物都具有逃跑行为[1],只是为了适应种间不同的生存环境,不同动物演化出了不同运动形式的逃跑行为来躲避攻击,比如蜘蛛在逃跑时利用重力垂直落地,鱼类通过短时爆发式游泳逃逸,而啮齿类则迅速跑向附近的庇护所.

内镜超声的应用明显提高了消化道病变的诊断水平,内镜超声引导下细针穿刺(endoscopic ultrasonography guided fine needle aspiration, EUS-FNA)可以对消化道病变同时进行超声、细胞学涂片及组织学活检,更好地帮助诊断及指导治疗,因此胃肠道间质瘤(gastrointestinal stromal tumor, GIST)诊断水平明显增高.GIST主要发生于胃和肠道,是胃肠道最常见的间叶源性肿瘤[1].食管原发性GIST较为少见,约占食管间叶性肿瘤的25％,仅占GIST总病例的不到1％[2].关于食管原发性GIST行EUS-FNA细胞学诊断的病例,国内缺乏其细胞学相关报道,现将南京大学医学院附属鼓楼医院收治的1例食管原发性GIST报道如下.

〔目的〕探究微卫星不稳定性(MSI)与晚期结直肠癌(mCRC)患者姑息化疗疗效及预后的相关性.〔方法〕选取154例mCRC姑息化疗患者进行回顾性分析,用免疫组化方法检测肿瘤组织中错配修复基因(MMR)MLH1、MSH2,MSH6、PMS2、蛋白表达,分析MSI与临床特征、化疗反应及预后相关性.〔结果〕免疫组化检测结果显示:14例为dMMR/MSI-H,占9.09％;140例为pMMR,占90.91％.MSI-H组、MSS组组间患者性别、年龄、癌细胞分化程度、肿瘤转移部位、病理类型无显著差异(P>0.05),MSI-H组、MSS组的肿瘤部位存在明显差异(P<0.05);MSI-H组、MSS组总有效率无显著差异(P>0.05),MSI-H组疾病控制率高于MSS组(P<0.05);MSI-H组1 a无进展生存率85.71％(12/14);MSS组1 a无进展生存率57.86％(81/140),MSI-H组1 a无进展生存率高于MSS组(P<0.05).〔结论〕MSI在mCRC姑息化疗患者的化疗疗效及预后影响中可能发挥着重要作用,有必要常规进行MSI-H检测.

目的 探讨急性脑梗死患者采用不同剂量重组组织纤溶酶原激活剂(rt-PA)静脉溶栓治疗的临床疗效.方法 回顾性分析于2016年1月-2019年1月间河南大学第一附属医院收治的急性脑梗死患者130例临床资料,根据溶栓剂量的不同分为小剂量组和大剂量组,每组各65例.小剂量组予rt-PA 0.6 mg/kg静脉溶栓治疗,大剂量组予rt-PA 0.9 mg/kg静脉溶栓治疗.对比观察两组临床疗效、神经功能以及用药不良反应.结果 小剂量组临床有效率略高于大剂量组,NIHSS评分稍高于大剂量组,但差异无统计学意义(P>0.05);小剂量组用药期间用药不良反应发生率低于大剂量组,差异有统计学意义(P<0.05).结论 rt-PA静脉溶栓治疗急性脑梗死效果显著,可有效改善患者缺血性脑损害,且运用小剂量rt-PA静脉溶栓可进一步提高临床疗效,安全性高.

Anxiety commonly co-occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop. The NAc core receives direct hypothalamic histaminergic projections, and optogenetic activation of hypothalamic NAc core histaminergic afferents selectively suppresses glutamatergic rather than GABAergic synaptic transmission in the NAc core via the H3 receptor and thus produces an anxiolytic effect and improves anxiety- and obsessive-compulsive-like behaviors induced by restraint stress. Although the H3 receptor is expressed in glutamatergic afferent terminals from the PrL, basolateral amygdala (BLA), and ventral hippocampus (vHipp), rather than the thalamus, only the PrL- and not BLA- and vHipp-NAc core glutamatergic pathways among the glutamatergic afferent inputs to the NAc core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Furthermore, activation of the H3 receptor ameliorates anxiety and obsessive-compulsive-like behaviors induced by optogenetic excitation of the PrL-NAc glutamatergic afferents. These results demonstrate a common mechanism regulating anxiety- and obsessive-compulsive-like behaviors and provide insight into the clinical treatment strategy for OCD with comorbid anxiety by targeting the histamine H3 receptor in the NAc core.

Ataxia, characterized by uncoordinated movement, is often found in patients with cerebellar hemorrhage (CH), leading to long-term disability without effective management. Microglia are among the first responders to CNS insult. Yet the role and mechanism of microglia in cerebellar injury and ataxia after CH are still unknown. Using Ki20227, an inhibitor for colony-stimulating factor 1 receptor which mediates the signaling responsible for the survival of microglia, we determined the impact of microglial depletion on cerebellar injury and ataxia in a murine model of CH. Microglial depletion reduced cerebellar lesion volume and alleviated gait abnormality, motor incoordination, and locomotor dysfunction after CH. Suppression of CH-initiated microglial activation with minocycline ameliorated cerebellum infiltration of monocytes/macrophages, as well as production of proinflammatory cytokines and chemokine C-C motif ligand-2 (CCL-2) that recruits monocytes/macrophages. Furthermore, both minocycline and bindarit, a CCL-2 inhibitor, prevented apoptosis and electrophysiological dysfunction of Purkinje cells, the principal neurons and sole outputs of the cerebellar cortex, and consequently improved ataxia-like motor abnormalities. Our findings suggest a detrimental role of microglia in neuroinflammation and ataxic motor symptoms after CH, and pave a new path to understand the neuroimmune mechanism underlying CH-induced cerebellar ataxia.

目的 研究依达拉奉联合奥扎格雷钠治疗急性进展性脑梗塞的疗效.方法 在本院2017年1月～2018年12月收治的急性进展性脑梗塞患者中选出160例为对象,以随机数表法将患者分入两组,对照组患者给予常规治疗+奥扎格雷钠治疗,观察组患者在对照组基础上应用依达拉奉治疗,对比两组的治疗效果.结果 治疗14d后,观察组患者的治疗总有效率为97.5％,高于对照组的治疗总有效率87.5％(P<0.05);观察组治疗14d后的NIHSS评分低于对照组,Barthel指数高于对照组(P<0.05);观察组患者治疗7d、14d后的TNF-α水平和IL-6水平均低于对照组(P<0.05).结论 依达拉奉联合奥扎格雷钠治疗急性进展性脑梗塞疗效确切,促进患者神经功能修复,提高生活质量.

Vestibular compensation is responsible for the spontaneous recovery of postural, locomotor, and oculomotor dysfunctions in patients with peripheral vestibular lesion or posterior circulation stroke. Mechanism investigation of vestibular compensation is of great importance in both facilitating recovery of vestibular function and understanding the postlesion functional plasticity in the adult CNS. Here, we report that postsynaptic histamine H1 receptor contributes greatly to facilitating vestibular compensation. The expression of H1 receptor is restrictedly increased in the ipsilesional rather than contralesional GABAergic projection neurons in the medial vestibular nucleus (MVN), one of the most important centers for vestibular compensation, in unilateral labyrinthectomized male rats. Furthermore, H1 receptor mediates an asymmetric excitation of the commissural GABAergic but not glutamatergic neurons in the ipsilesional MVN, which may help to rebalance bilateral vestibular systems and promote vestibular compensation. Selective blockage of H1 receptor in the MVN significantly retards the recovery of both static and dynamic vestibular symptoms following unilateral labyrinthectomy, and remarkably attenuates the facilitation of betahistine, whose effect has traditionally been attributed to its antagonistic action on the presynaptic H3 receptor, on vestibular compensation. These results reveal a previously unknown role for histamine H1 receptor in vestibular compensation and amelioration of vestibular motor deficits, as well as an involvement of H1 receptor in potential therapeutic effects of betahistine. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery in the CNS, but also a novel potential therapeutic target for vestibular disorders.SIGNIFICANCE STATEMENT Vestibular disorders manifest postural imbalance, nystagmus, and vertigo. Vestibular compensation is critical for facilitating recovery from vestibular disorders, and of great importance in understanding the postlesion functional plasticity in the adult CNS. Here, we show that postsynaptic H1 receptor in the medial vestibular nucleus (MVN) contributes greatly to the recovery of both static and dynamic symptoms following unilateral vestibular lesion. H1 receptor selectively mediates the asymmetric activation of commissural inhibitory system in the ipsilesional MVN and actively promotes vestibular compensation. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery of CNS, but also a novel potential therapeutic target for promoting vestibular compensation and ameliorating vestibular disorders.

Corticotropin-releasing factor (CRF) is a neuropeptide mainly synthesized in the hypothalamic paraventricular nucleus and has been traditionally implicated in stress and anxiety. Intriguingly, genetic or pharmacological manipulation of CRF receptors affects locomotor activity as well as motor coordination and balance in rodents, suggesting an active involvement of the central CRFergic system in motor control. Yet little is known about the exact role of CRF in central motor structures and the underlying mechanisms. Therefore, in the present study, we focused on the effect of CRF on the lateral vestibular nucleus (LVN) in the brainstem vestibular nuclear complex, an important center directly contributing to adjustment of muscle tone for both postural maintenance and the alternative change from the extensor to the flexor phase during locomotion. The results show that CRF depolarizes and increases the firing rate of neurons in the LVN. Tetrodotoxin does not block the CRF-induced depolarization and inward current on LVN neurons, suggesting a direct postsynaptic action of the neuropeptide. The CRF-induced depolarization on LVN neurons was partly blocked by antalarmin or antisauvagine-30, selective antagonists for CRF receptors 1 (CRFR1) and 2 (CRFR2), respectively. Furthermore, combined application of antalarmin and antisauvagine-30 totally abolished the CRF-induced depolarization. Immunofluorescence results show that CRFR1 and CRFR2 are co-localized in the rat LVN. These results demonstrate that CRF excites the LVN neurons by co-activation of both CRFR1 and CRFR2, suggesting that via the direct modulation on the LVN, the central CRFergic system may actively participate in the central vestibular-mediated postural and motor control.