杏仁核c-fos的表达与条件反射性免疫抑制

以糖精水为条件刺激（conditioned stimulus,,CS）,免疫抑制剂-环磷酰胺为非条件刺激 （(unconditioned stimulus,,UCS),在两次CS-UCS结合训练后,观测不同时程再次单独呈现条件刺激对条件反射性免疫抑制和味觉厌恶性行为反应的变化以及大鼠杏仁核各亚核团内c-fos蛋白表达的影响。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。条件反射组大鼠杏仁中央核c-fos蛋白表达在第5天非常密集,而第30天明显减少,与细胞免疫功能改变在时程和趋势上具有一致性。通过c-fos蛋白表达时程差异比较,提示杏仁中央核可能既与条件性的味觉厌恶性行为建立有关,也是参与介导CS诱导的免疫抑制效应的重要核团。     

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     

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.     

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。     

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。     

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     

损毁大鼠双侧内嗅皮质对束缚应激反应的影响

采用大鼠急性束缚应激动物模型,用鹅羔氨酸损毁大鼠双侧内嗅皮质来建立内嗅皮质损伤模型,观察束缚应激1小时后下丘脑室旁核快反应基因c-Fos表达情况以及应激后血浆促肾上腺皮质激素含量的动态变化,并与对照组相比较,探讨内嗅皮质与束缚应激反应的关系。结果表明,损毁内嗅皮质,明显抑制了应激诱导的下丘脑室旁核c-Fos的表达和血浆促肾上腺皮质激素含量的上升。结果提示,内嗅皮质参与调节束缚应激反应时HPA轴功能。     

Inactivation of the anterior cingulate cortex blocks expression of remote, but not recent, conditioned taste aversion memory

Previous studies have shown that medial prefrontal cortical regions, such as the anterior cingulate cortex (ACC), play a key role in the expression of remote spatial and contextual memory. To evaluate whether this role is conserved in hippocampal-independent tasks we trained mice in the conditioned taste aversion (CTA) paradigm. Lidocaine-induced inactivation of the ACC blocked the expression of CTA tested one month (remote), but not one day (recent), after conditioning with either a weak or strong unconditioned stimulus (US). These data suggest that the ACC may play a conserved role in remote memory, regardless of memory strength or content.     

Classical discrimination conditioning of the rabbit's eyelid response using pontine stimulation as a conditioned stimulus

Classical discrimination conditioning of the nictitating membrane/eyelid response was performed on seven rabbits using stimulation of the pontine nuclei or middle cerebellar peduncle as the conditioned stimulus (CS) and an air puff as the unconditioned stimulus (US). The rabbits learned to discriminate between a CS paired with a US and delivered to one pontine nucleus (the CS+) and a CS presented alone and delivered to the contralateral pontine nucleus (the CS-). Subsequent reversal of the discrimination was also achieved when the CS+ and CS- stimulation sites were interchanged. The results are interpreted as support for the idea that essential plasticity for classical eyelid conditioning occurs efferent to the pontine nuclei, possibly in regions of the cerebellum.     

Rho-associated kinase in the gustatory cortex is involved in conditioned taste aversion memory formation but not in memory retrieval or relearning

Rho-associated kinase (ROCK) is intimately involved in cortical neuronal morphogenesis. The present study explores the roles of ROCK in conditioned taste aversion (CTA) memory formation in gustatory cortex (GC) in adult rat. Microinjection of the ROCK inhibitor Y-27632 into the GC 30 min before CTA training or 10 min after the conditioned stimulus (CS) impaired long-term CTA memory (LTM) formation. ROCK inhibitor had no effect on taste aversion when injected before the first LTM test day and did not alter taste aversion on subsequent test days. Microinjection of ROCK inhibitor into GC 30 min before preexposure to the taste CS had no effect on latent inhibition of CTA learning suggesting that ROCK is involved in CS-US association rather than taste learning per se. Cumulatively, these results show that ROCK is needed for normal CTA memory formation but not retrieval, relearning or incidental taste learning.     

Comparison of Single Unit Responses to Tone, Light, and Compound Conditioned Stimuli during Rabbit Classical Eyeblink Conditioning

Unit recordings and lesion studies have implicated the cerebellum as an essential site for the acquisition and maintenance of the conditioned eyeblink response. The current study looked at the neural characteristics of conditioned stimulus (CS) processing in the interpositus nucleus of the cerebellum after training New Zealand white rabbits (Oryctolagus cuniculus) in one of two conditioning paradigms: (a) compound conditioning (CMP), a compound CS consisting of light and tone paired with an air puff unconditioned stimulus (US); or (b) stimulus compounding (ALT), alternating blocks of tone CS and light CS trials paired with the air puff US. Single unit responses were recorded during five sessions after the animals had reached an asymptotic level of responding. Animals were tested for behavioral and neural responses to CS alone trials that included tone alone, light alone, and compound tone-light trials. For the CMP group, the compound CS elicited 80 to 90% conditioned eyeblink responses (CRs), whereas the individual tone and light CSs elicited only 40 to 50% CRs. For the ALT group, all three CSs (tone, light, and compound) elicited very high levels of responding of at least 80% CRs. For the CMP group, there were roughly equal numbers of cells responding to all of the CSs. This includes cells that responded exclusively to one, and only one, of the three stimuli and also those cells that responded to combinations of two or more. Cells from the ALT group were far more likely to respond exclusively to only one of the CSs. Both the behavioral and physiological results suggest that the compound tone-light stimulus was processed as a distinct stimulus, separate from the component tone and light. These results are discussed in the context of multisensory processing.     

Timing of fear expression in trace and delay conditioning measured by fear-potentiated startle in rats

In two experiments, the time course of the expression of fear in trace (hippocampus-dependent) versus delay (hippocampus-independent) conditioning was characterized with a high degree of temporal specificity using fear-potentiated startle. In experiment 1, groups of rats were given delay fear conditioning or trace fear conditioning with a 3- or 12-sec trace interval between conditioned stimulus (CS) offset and unconditioned stimulus (US) onset. During test, the delay group showed fear-potentiated startle in the presence of the CS but not after its offset, whereas the trace groups showed fear-potentiated startle both during the CS and after its offset. Experiment 2 compared the time course of fear expression after trace conditioning with the time course in two delay conditioning groups: one matched to the trace conditioning group with respect to CS duration, and the other with respect to ISI. In all groups, fear was expressed until the scheduled occurrence of the US and returned to baseline rapidly thereafter. Thus, in both trace and delay fear conditioning, ISI is a critical determinant of the time course of fear expression. These results are informative as to the possible role of neural structures, such as the hippocampus, in memory processes related to temporal information.     

Conditioning the unconditioned response: modification of the rabbit's (Oryctolagus cuniculus) unconditioned nictitating membrane response

Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to an unconditioned stimulus (US) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit nictitating (Oryctolagus cuniculus) membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or US manipulation. CRM occurred after 12 days of CS-US pairings but not following unpaired CS/US presentations or restraint. CRM survived CS-alone and CS/US-unpaired extinction of the conditioned response (CR) but not presentations of the US alone, although CRs remained intact. Thus, CRs could be weakened without eliminating CRM and CRM could be weakened without eliminating CRs. Data indicate CRM is a reliable, associative effect that is more than a generalized CR and may not be explained by habituation, stimulus generalization, contextual conditioning, or bidirectional conditioning.