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。     

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     

评价性条件反射效应：无条件刺激的呈现时长、效价强度与关联意识的作用

以真实商标图案为条件刺激, 情绪图片为无条件刺激, 探索无条件刺激呈现时长、效价强度与关联意识对评价性条件反射效应的影响。实验通过结合四图再认测验与基于项目分析, 对关联意识的作用进行了详细探讨。结果表明, 评价性条件反射效应只发生在无条件刺激长呈现水平与无条件刺激强效价水平; 评价性条件反射效应的产生需要基于被试的关联意识。关联意识在呈现时长(效价强度)与评价性条件反射效应间的中介作用不显著。结果不支持评价性条件反射的内隐错误归因机制及联想-命题评价模型的相关论断, 部分支持命题性解释模型。     

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。     

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。     

人腦电活动与心理現象(下)

(五)条件反射与学习人脑电活动的条件反射与学习研究绝大部分均狭隘地仅以α波阻抑现象为指标。早期的研究(H.Jasper与C.Shagass,1941,与1943等)便曾证明借传统的α波阻抑现象可见条件反射的建立。一般常用的方法为用不引起α波阻抑现象的轻声作为条件刺激,用能引起α波阻抑现象的光刺激作为非条件强化。当轻声与光刺激多次结合后,若单独轻声刺激连续2—5次引起α波阻抑现象便表示条件反射的建立。借上述方法也可探讨分化或延缓条件反射等。例如用高音作为阳性刺激信号与用低音作为阴性刺激信号或用节拍器为条件刺激,延迟10—20秒再进行非条件强化等(K.     

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...     

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。     

Timing of Conditioned Responses Utilizing Electrical Stimulation in the Region of the Interpositus Nucleus as a CS

A large body of evidence indicates that the cerebellum is essential for the acquisition, retention, and expression of the standard delay conditioned eyeblink response and that the basic memory trace appears to be established in the anterior interpositus nucleus (IP). Adaptive timing of the conditioned response (CR) is a prominent feature of classical conditioning-the CR peaks at the time of onset of the unconditioned stimulus (US) over a wide range of CS-US interstimulus intervals (ISI). A key issue is whether this timing is established by the cerebellar circuitry or prior to the cerebellum. In this study timing of conditioned eyeblink responses established via electrical stimulation of the interpositus nucleus as a conditioned stimulus (CS) was analyzed prior to and following modification of the CS-US interval in well-trained rabbits. Consistent with previous results, learning under these conditions is very rapid and robust. The CR peak eyeblink latencies are initially timed to the US onset and adjust accordingly to lengthening or shortening of the CS-US interval, just as with peripheral CSs. The acquisition of conditioned eyeblink responses by direct electrical stimulation of the IP as a CS thus retains temporal flexibility following shifts in the CS-US delay, as found in standard classical eyeblink conditioning procedures.     

Timing of conditioned responses utilizing electrical stimulation in the region of the interpositus nucleus as a CS

A large body of evidence indicates that the cerebellum is essential for the acquisition, retention, and expression of the standard delay conditioned eyeblink response and that the basic memory trace appears to be established in the anterior interpositus nucleus (IP). Adaptive timing of the conditioned response (CR) is a prominent feature of classical conditioning—the CR peaks at the time of onset of the unconditioned stimulus (US) over a wide range of CS-US interstimulus intervals (ISI). A key issue is whether this timing is established by the cerebellar circuitry or prior to the cerebellum. In this study timing of conditioned eyeblink responses established via electrical stimulation of the interpositus nucleus as a conditioned stimulus (CS) was analyzed prior to and following modification of the CS-US interval in well-trained rabbits. Consistent with previous results, learning under these conditions is very rapid and robust. The CR peak eyeblink latencies are initially timed to the US onset and adjust accordingly to lengthening or shortening of the CS-US interval, just as with peripheral CSs. The acquisition of conditioned eyeblink responses by direct electrical stimulation of the IP as a CS thus retains temporal flexibility following shifts in the CS-US delay, as found in standard classical eyeblink conditioning procedures.     

Escape from serial stimuli leading to food

If the functional relations governing the strength of a conditioned reinforcer correspond to those obtained with other Pavlovian procedures (e.g., Kaplan, 1984), the termination of stimuli appearing early in the interval between successive food deliveries should be reinforcing. During initial training we presented four key colors, followed by food, in a recurrent sequence to each of 6 pigeons. This established a baseline level of autoshaped pecking. In later sessions, we terminated each of these colors or only the first color for a brief period following each peck, replacing the original color with a standard substitute to avoid darkening the key. Pecking decreased in the presence of the last color in the sequence but increased in the presence of the first. In accord with contemporary models of Pavlovian conditioning, these and other data suggest that the behavioral effects of stimuli in a chain may be better understood in terms of what each stimulus predicts, as measured by relative time to the terminal reinforcer, than in the exclusively positive terms of the traditional formulation (Skinner, 1938). The same model may also account for the initial pause under fixed-interval and fixed-ratio schedules of reinforcement.     

Facilitation of instrumental behavior by a Pavlovian appetitive conditioned stimulus

Three experiments examined appetitive Pavlovian-instrumental interactions by presenting separately trained conditioned stimuli (CSs) during reinforced instrumental responding in rabbits. Intra-oral reinforcement was used to minimize interference from peripheral responses such as magazine approach. In experiment 1, the rabbits were first trained to perform an instrumental head-raising response for sucrose reward. A conditioned jaw movement response was then established to a 2-sec CS by pairing it with sucrose; a control stimulus was unpaired with sucrose. Instrumental responding maintained by a variable-interval 40-sec schedule was enhanced during 10-sec presentations of the paired, but not the unpaired, CS. Responding on a variable-ratio 15 schedule was unaffected except on trials on which the pre-CS baseline response rate was low; in such cases the paired CS caused a long-lasting acceleration of responding. Noncontingent presentation of the sucrose reinforcer itself briefly suppressed responding but had no long-term effect. In Experiment 2, a CS that had been conditioned at a 10-sec duration produced the same pattern of effects as in the first study, indicating that facilitation resulted from CS presentation rather than from the frustrative effects of non-reinforcement of the CS. In Experiment 3 an inhibitory CS blocked facilitation by the excitatory CS but did not itself affect instrumental responding. These results support the view that Pavlovian processes play a positive role in instrumental performance and suggest that previous findings of suppression by a short-duration CS reflect peripheral interference. The dependence of facilitation on the baseline level of responding is discussed in terms of associative and motivational theories of Pavlovian mediation.     

Acquisition of the classically conditioned eyeblink response in humans over the life span

Human subjects ranging in age from 18 to 85 years underwent classical conditioning of the eyeblink response to a tone conditioned stimulus (CS) and an air-puff unconditioned stimulus (UCS). There was a decline in percentage of conditioned responses with age. This decline was most noticeable in subjects over age 50. These conditioning deficits were not due to age-related changes in sensitivity to the tone CS or the air-puff UCS, nor could the conditioning deficits be attributed to an age-related decline in general cognitive abilities or to changes in spontaneous blink rates. The results are discussed in terms of using the classically conditioned eyeblink in humans in conjunction with the classically conditioned nictitating membrane response in rabbits as a model system for studying the neurobiology of age-related conditioning deficits.     

Role of the hippocampus in blocking and conditioned inhibition of the rabbit's nictitating membrane response.

Bilateral aspiration of the dorsal hippocampus produced a disrupttion of blocking of the rabbit's nictitating membrane response in Kamin's two-stage paradigm (Experiment 1) but had no effect on the formation of a Pavlovian conditioned inhibitor (Experiment 2). The results of Experiment 1 indicated that normal animals and those with cortical lesions given conditioning to a light-plus-tone conditioned stimulus (CS) gave conditioned responses (CRs) to both the light and the tone during nonreinforced presentations of each (test phase). If, however, compound conditioning was preceded by tone acquisition, only the tone elicited a CR during testing; that is, blocking was observed. In rabbits with hippocampal lesions, however, CRs were given to both the light and the tone during testing whether or not compound conditioning was preceded by tone acquisition. The data from Experiment 2 showed that rabbits with hippocampal lesions could discriminate as well as normal rabbits and those with cortical lesions between a light (CS+) and light plus tone (CS-). In addition, when the inhibitory tone was subsequently paired with the unconditioned stimulus in retardation testing, animals in all three lesion conditions acquired the CR at the same rate. Thus, it appears that hippocampal lesions do not disrupt conditioned inhibition. The results of these experiments were taken as support for the view that the hippocampus is responsible for "tuning out" stimuli that have no adaptive value to the organism.     

Cerebellar lesions abolish an avoidance response in rabbit

Unilateral lesions of the cerebellar dentate-interpositus (DI) nuclei abolished or impaired the reacquisition of a nictitating membrane (NM) conditioned avoidance response (CAR) in rabbits. Animals that sustained damage to the DI nuclei and surrounding areas displayed little or no reacquisition of the NM-CAR ipsilateral to the lesion, but displayed excellent acquisition of the response when training was shifted to the contralateral eye. These results agree with previous investigations of the effects of cerebellar lesions on the classically conditioned NM and leg-flexion responses. The DI nuclei appear to be essential for the retention of conditioned responses in a variety of associative paradigms.     

Latent inhibition and stimulus generalization of the classically conditioned nictitating membrane response in rabbits (Oryctolagus cuniculus) following dorsal hippocampal ablation.

Rabbits received 0 to 450 exposures of a tone conditioned stimulus (CS) prior to classical defensive conditioning of the nicitating membrane response based on an infraorbital eye shock unconditioned stimulus. Tone preexposure resulted in retarded conditioning in normal rabbits. This latent inhibition effect was not present in animals with bilateral dorsal hippocampectomy produced by aspiration. Control animals with bilateral neocortical and callosal aspiration lesions demonstrated a latent inhibition effect similar to that shown by normal nonoperated animals. The failure of CS preexposure to retard conditioning in hippocampal rabbits was not due to differences in threshold of the conditioned response to the CS or to differences in response mechanisms as determined by tests of habituation and dishabituation of the unconditioned response. A subsequent experiment employed combined-cue summation tests to confirm the fact that preexposure did not endow the tone with conditioned as well as latent inhibitiory properties. Finally, tests of stimulus generalization along the auditory frequency dimension indicated flatter relative gradients for hippocampals than for nonoperated controls, with cortical controls in between. These findings were discussed in terms of Douglas' model of hippocampal function.     

Resistance to extinction of conditioned odor perceptions: evaluative conditioning is not unique

A tasteless odor will smell sweeter after being sampled by mouth with sucrose and will smell sourer after being sampled with citric acid. This tasty-smell effect was found in experiments that compared odor-taste and color-taste pairings. Using odors and colors with minimal taste (Experiment 1), the authors found that repeated experience of odor-taste mixtures produced conditioned changes in odor qualities that were unaffected by intermixed color-taste trials (Experiment 2). An extinction procedure, consisting of postconditioning presentations of the odor in water, had no detectable effect on the changed perception of an odor (Experiments 3 and 4). In contrast, this procedure altered judgments about the expected taste of colored solutions. Evaluative conditioning (conditioned changes in liking) is claimed to be resistant to extinction. However, these results suggest that resistance to extinction in odors is related to the way they are encoded rather than to their hedonic properties.     

Effects of paradigm and inter-stimulus interval on age differences in eyeblink classical conditioning in rabbits

The aim of this study was to examine parameters affecting age differences in eyeblink classical conditioning in a large sample of young and middle-aged rabbits. A total of 122 rabbits of mean ages of 4 or 26 mo were tested at inter-stimulus intervals (ISIs) of 600 or 750 msec in the delay or trace paradigms. Paradigm affected both age groups dramatically, with superior performance in the delay paradigm. ISI was salient as middle-aged rabbits were significantly impaired in 750-msec compared with 600-msec delays, and young rabbits were significantly less impaired in 600-msec than in 750-msec trace. Young rabbits performed equally well at both delay ISIs, and consequently, there were significant age differences in 750-msec but not in 600-msec delays. Middle-aged rabbits performed poorly at both 600- and 750-msec trace, resulting in significant age differences in 600-msec but not in 750-msec trace. Timing of the conditioned response has been associated with cerebellar cortical function. Normal aging of the cerebellar cortex likely contributed to the magnitude of the effect of ISI in delay conditioning in middle-aged rabbits. Results demonstrate that the magnitude of age differences in eyeblink conditioning can be enlarged or eliminated by ISI and paradigm.