条件反射性免疫抑制激活过程中下丘脑核团c-fos的表达

利用经典条件反射性免疫抑制的动物模型,以糖精水为条件刺激（CS）,免疫抑制剂-环磷酰胺为非条件刺激 （UCS）,观测两次CS-UCS结合训练后,再次条件刺激诱发条件反射性免疫抑制作用的动态改变,获得条件反射性免疫抑制和味觉厌恶性条件反射各自保持的情况,并在此基础上,采用c-fos免疫组化技术, 进一步观察再次条件刺激诱发条件反射性免疫抑制反应时大鼠下丘脑各核团内FOS蛋白的表达情况。结果表明,条件反射性免疫抑制作用在训练后第5天较强,第30天基本消失,而味觉厌恶性条件反射始终稳定保持到第30天。进一步研究显示出,下丘脑室旁核FOS蛋白表达在第5天非常密集,而第30天几乎没有表达,与细胞免疫功能改变在时程和趋势上具有一致性。通过FOS蛋白表达时程差异比较,提示下丘脑室旁核可能是CNS内介导CS诱导的免疫抑制效应的重要核团。     

对体液免疫反应的条件反射性调节

以饮糖精水作为条件刺激(conditioned stimulus,CS),腹腔注射免疫抑制剂环磷酰胺作为非条件刺激(unconditioned stimulus,UCS)训练Wistar大鼠,3天后腹腔注射卵清蛋白(ovalbunfin,OVA)抗原,观察再次单独条件刺激对原发性体液免疫反应的作用。结果发现．一次CU-UCS结合训练导致CS组大鼠对再现糖精水产生厌恶反应,外周血中抗OVA-IgG抗体水平显著低于UCS组。两次CS-UCS结合训练并多次给予条件刺激后,CS组大鼠抗OVA-IgG的条件性免疫抑制效应与一次CS-UCS结合训练及再次给予一次条件刺激的反应类同。这些结果证明条件刺激增强了环磷酰胺对动物原发性体液免疫反应的抑制作用．这种条件性体液免疫抑制作用是相对稳定和有限度的,不易受条件反射建立参数的影响。     

厌恶性条件反射与脑中c-fos的表达

Ｆｏｓ免疫组织化学法作为一种神经功能活动形态定位法,已在大鼠厌恶性条件反射的神经机制的研究中得到应用。无论是在味觉厌恶性条件反射的研究中,还是在听觉刺激与电击相结合的厌恶性条件反射的研究中,都证明了条件反射建立后,条件刺激能诱导出与非条件刺激相似的ｃ－ｆｏｓ表达的分布,这提示条件反射学习沟通了条件刺激和非条件刺激这两种不同刺激在大脑中的传导通路。     

以兔抗鼠淋巴细胞血清为非条件刺激的条件性免疫抑制

采用一种生物类免疫抑制剂-兔抗鼠淋巴血清（rabbit anti-rat lymphocyte serum,ALS）为非条件刺激（UCS）,糖精水为条件刺激（CS）,以双瓶给水法置于鼠笼前端饮用偏好侧。在一次性CS-UCS结合训练后,单独再次给予CS,使卵清蛋白（OVA）免疫过的大鼠表现出脾淋巴细胞对有丝分裂原PWM的增殖反应降低,血抗OVA抗体的总量及脾内抗OVA抗体生成细胞的减少,但动物未表现出条件性味觉厌恶的行为反应。这些结果表明条件性免疫抑制与味觉厌恶行为条件反射没有必然联系,并非是厌恶行为反应或情绪应激的伴随产物。UCS也并非必需具有感觉的毒副作用,条件性免疫抑制是脑高级神经活动调节免疫功能的结果。     

味觉厌恶性条件反射建立后脑内c-Fos的表达

以新异味觉刺激糖精水的摄入为条件刺激,以腹腔注射环磷酰胺(CY,免疫抑制剂)或氯化锂(LiCl)为非条件刺激,分别使大鼠建立味觉厌恶性条件反射.在条件刺激日,糖精水在学习组大鼠下列脑区中诱发出密集的Fos表达下丘脑、杏仁核、边缘皮质等,而非学习组在这些区域中却没有或只有少量表达.另外,在丘脑前背侧核、扣带回、下丘脑外侧核、穹隆下器、压部后颗粒皮质、视上核,CY组的Fos表达明显多于LiCl组;而在伏核、杏仁基底外侧核、腹外侧隔核,LiCl组的Fos表达明显多于CY组,这种差异可能是两种药物的不同药理性质所致.     

条件性味觉厌恶分化后臂旁核c-fos表达的变

以口内注入糖精或蔗糖溶液为条件刺激,腹腔内注射LiCl为非条件刺激,在大鼠形成条件性味觉厌恶后进行分化训练,观察味质和嗜好性对臂旁核各亚核c-fos表达的影响及其交互作用。结果表明：味质和嗜好性对背侧外侧亚核(dls)和腹侧外侧亚核(vls)的c-fos表达无影响;在内侧外侧亚核(ils)和外部内侧亚核(ems),蔗糖诱导的c-fos表达高于糖精,但在外部外侧亚核(els),糖精诱导的表达高于蔗糖;嗜好性刺激引起ils、中央外侧亚核(cls)和cms内c-fos高表达,厌恶性刺激引起ems和els内的高表达。在ils和cms嗜好性与味质的影响各自独立,在els和ems内嗜好性与味质的影响存在交互作用。提示PBN内存在味质辨别和报酬评价的代表区,两种代表区有交迭,ems和els对味质信息和报酬信息的整合有重要作用     

味觉厌恶性条件反射与条件反射性免疫抑制的研究

以环磷酰胺的注射为非条件刺激（ＵＣＳ）,糖精水的摄入为条件刺激（ＣＳ）,并以血白细胞和淋巴细胞数量及脾淋巴细胞的转化反应为免疫指标,糖精水的饮用量为行为指标,通过改变条件刺激与非条件刺激结合的次数来观察条件反射性厌恶行为与条件反射性免疫抑制的反应。结果表明不管是一次性的还是两次性的ＣＳ－ＵＣＳ结合训练都能使动物明显地建立起味觉厌恶性条件反射,然而条件反射性免疫抑制只在两次性ＣＳ－ＵＣＳ结合训练后才     

厌恶性条件反射与脑中c-fos的表达

ｆｏｓ免疫组织化学法作为一种神经功能活动形态定位法,已在大鼠厌恶性条件反射的神经机制的研究中得到应用。无论是在味觉厌恶性条件反射的研究中,还是在听觉剌激与电击相结合的厌恶性条件反射的研究中,都证明了条件反射建立后,条件剌激能诱导出与非条件剌激相似的ｃ－ｆｏｓ表达的分布,这提示条件反射学习沟通了条件剌激和非条件剌激这两种不同剌激在大脑中的传导通路。     

条件反射性抗体反应增强的动态分析——以OVA为非条件刺激物

研究了条件反射性抗体反应增强模型的建立。被试为49只雄性成年Wistar大鼠,采用糖精水作为条件性刺激,一种蛋白抗原卵清蛋白作为非条件性刺激配对给予大鼠,两者结合后,在初次抗体应答下降阶段再次单独给予条件刺激,用酶联免疫吸附法分时段检测抗体水平的变化。发现条件组在条件刺激后15,20,25天左右抗体水平明显高于对照组。这一过程与初次抗体应答的规律类似。这些结果证实经一次条件训练,单独给予条件刺激能诱导出明显的条件反射性抗体反应增高。     

NO对家兔眨眼条件反射获得的影响

与此文有关的交流及通讯,请和沈政教授联系。１前言眨眼条件反射是动物习得的一种反应。条件刺激声音（ＣＳ）和非条件刺激角膜吹气（ＵＳ）多次结合训练家兔,可使它形成条件反射（ＣＲ）,即给出ＣＳ,不给吹气,动物也会产生眨眼反射。行为、核团损毁、电生理等实验证...     

Skin conductance response conditioning with CS intensities equal to and greater than UCS intensity

With .2-sec bursts of white noise as both conditioned stimulus (CS) and unconditioned stimulus (UCS), conditioning of first-interval skin conductance responses was obtained when the intensity of the CS equaled and exceeded that of the UCS. There was no evidence that second-interval response conditioning occurred. Nonspecific response frequencies were also affected by the variations in stimulus intensity, this raising some question about typical controls employed in SCR conditioning. There was some evidence that second interval responses were suppressed by the intense CS values. It was concluded that the existence of simple conditioning with a CS/UCS intensity ratio equal to or greater than unity was contrary to the Pavlovian proposition that a CS must be biologically less salient than the UCS in order for conditioning to occur. It was noted, however, that the suppression of second-interval responses might indicate that anticipatory CRs which are not confounded with orienting reflexes are prevented from exhibiting a conditioning effect when a high CS/UCS intensity ratio is employed.     

Neuronal unit activity in the abducens nucleus during classical conditioning of the nictitating membrane response in the rabbit (Oryctolagus cuniculus).

Neuronal unit activity was recorded from the abducens (6th nerve) nucleus, the "final common path," during classical conditioning of the nictitating membrane (NM) response in the rabbit, with the use of a tone conditioned stimulus, an air puff unconditioned stimulus (UCS), 250-msec interstimulus interval, and 60-sec intertrial interval. Animals were given 2 days of conditioning training (104 trials in eight blocks per day) and 1 day of extinction. Control animals were given comparable periods of stimulus presentations, explicitly unpaired. Activity of small clusters of units--"multiple unit" recording--was compared with the amplitude-time course of the NM response. Between-blocks comparisons of neural and behavioral responses indicated an essentially perfect correlation during acquisition of the conditioned response (Day 1, r = .99; Day 2, r = .98) and a slightly lower correlation during extinction (r = .93) for the conditioning animals. Within-blocks comparisons indicated a close correspondence between the histograms of unit activity and the amplitude-time course of the NM response for the conditioning animals in all phase of training and for the control animals in the UCS trial blocks.     

Associative learning acquisition and retention depends on developmental stage in Lymnaea stagnalis

Associative learning dependent on visual and vestibular sensory neurons and the underlying cellular mechanisms have been well characterized in Hermissenda but not yet in Lymnaea. Three days of conditioning with paired presentations of a light flash (conditional stimulus: CS) and orbital rotation (unconditional stimulus: UCS) in intact Lymnaea stagnalis results in a whole-body withdrawal response (WBWR) to the CS. In the current study, we examined the optimal stimulus conditions for associative learning, including developmental stage, number of stimuli, interstimulus interval, and intertrial interval. Animals with a shell length longer than 18 mm (sexually mature) acquired and retained the associative memory, while younger ones having a shell length shorter than 15 mm acquired but did not retain the memory to the following day. For mature animals, 10 paired presentations of the CS and UCS presented every 2 min were sufficient for the induction of a WBWR to the CS. Furthermore, animals conditioned with the UCS presented simultaneously with the last 2 s of the CS also exhibited a significant WBWR in response to the CS. Blind animals did not acquire the associative memory, suggesting that ocular photoreceptors, and not dermal photoreceptors, detected the CS. These results show that maturity was key to retention of associative learning.     

The role of awareness in delay and trace fear conditioning in humans

Expression of conditional fear without awareness has been previously demonstrated during delay conditioning, a procedure in which the conditioned stimulus (CS) and unconditioned stimulus (UCS) overlap. However, less is known about the role of awareness in trace fear conditioning, where an interval of time separates the CS and UCS. The present study assessed skin conductance response (SCR) and UCS expectancy during delay and trace conditioning. UCS predictability was varied on a trial-bytrial basis by presenting perithreshold auditory CSs. Differential UCS expectancies were demonstrated only on perceived delay and trace trials. Learning-related SCRs were observed during both perceived and unperceived delay CSs. In contrast, differential SCRs were demonstrated only for perceived trace CSs. These data suggest that awareness is necessary for conditional responding during trace, but not delay, fear conditioning.     

The interval between the CS and the UCS as a determiner of generalization performance

Rats were trained in a conditioned taste aversion paradigm in order to determine whether a trace interval between the conditioned stimulus (CS) and the unconditioned stimulus (UCS) would result in the forgetting of stimulus attributes. Accordingly, subjects were conditioned with milk (CS), given either an immediate or a delayed injection of lithium chloride (UCS), and tested 48 h later with either milk or chocolate milk, a generalized flavor. The rats conditioned immediately following the presentation of the CS avoided milk more than chocolate milk, indicating discrimination between the two flavors. Those conditioned after a trace interval avoided both flavors equally, suggesting a loss of stimulus attributes of the original CS. Delay rats, however, still exhibited substantial learning when compared with controls not experiencing the UCS. These results allege a role for the forgetting of stimulus attributes during a trace interval in addition to following a complete learning episode.     

Memory consolidation in both trace and delay fear conditioning is disrupted by intra-amygdala infusion of the protein synthesis inhibitor anisomycin

Memory for delay fear conditioning requires the synthesis of new mRNA and protein in the basolateral amygdala. It is currently unknown whether similar molecular processes in the amygdala are required for the formation of trace fear memory, in which a stimulus-free interval is inserted between the conditional stimulus (CS) and unconditional stimulus (UCS). Here, we show that infusion of the protein synthesis inhibitor anisomycin into the basolateral amygdala disrupts consolidation of both trace and delay fear conditioning. This is the first evidence that protein synthesis in the amygdala is necessary for the formation of both trace and delay fear memory.