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     

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。     

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     

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。     

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。     

情绪应激对不同脑区c-fos表达的影响

利用电击信号和空瓶刺激两种情绪应激体液免疫调节作用动物模型,以c-fos原癌基因为探针,观察情绪应激后2个小时,大鼠全脑的c—fos原癌基因表达情况,探讨情绪应激对不同脑区c—fos表达的影响。结果表明,电击信号和空瓶刺激两种情绪应激源均能引起某些脑区或核团的c—fos蛋白表达明显增加,包括额皮质、扣带皮质、杏仁内侧核、前连合核、下丘脑背内侧核弥散部、弓状核、孤束核。结果提示,这些脑区或核团是情绪应激主要激活的中枢部位。     

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。     

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。     

情景变换诱发已消退恐惧记忆重现的神经环路

暴露疗法是治疗创伤后应激障碍的主要行为疗法。当被试反复暴露于可引起恐惧反应的条件刺激(如白噪音), 但却不伴有非条件刺激(如足底电击)时, 恐惧记忆将被消退, 形成消退记忆。但恐惧记忆并未从根本上被擦除, 当被试在消退训练以外的情景暴露于条件刺激时, 已消退的恐惧记忆将会重现。海马、内侧前额叶皮层、杏仁核等脑区及其相互连接的神经环路是情景诱发恐惧记忆重现的生理基础。情景变化诱发恐惧记忆重现过程中, 海马可能是通过直接投射至杏仁核基底核、杏仁核外侧核或通过边缘前皮质间接调控杏仁核基底核、杏仁核外侧核的功能, 产生恐惧反应。     

动物信号追踪和目标追踪行为及其神经机制

信号追踪和目标追踪的实质是条件刺激和非条件刺激结合诱导的条件性接近反应.条件刺激的预测作用和诱因作用是信号追踪和目标追踪的重要机制;伏隔核、中央杏仁核和前扣带回在信号追踪和目标追踪过程中具有重要作用;然而,大脑皮层和海马损伤对两者影响较小.DA功能降低可损害信号追踪获得和表达;而脑内DA含量增加可提高目标追踪.未来的研究中,应该规范条件刺激和非条件刺激的类型和设置方法,针对不同的研究目的个别地或同时地测量信号追踪和目标追踪.     

Spatial learning of the water maze: Progression of brain circuits mapped with cytochrome oxidase histochemistry

The progression of brain circuits involved in spatial learning tasks is still a matter of debate. In addition, the participation of individual regions at different stages of spatial learning remains a controversial issue. In order to address these questions, we used quantitative cytochrome oxidase histochemistry as a metabolic brain mapping method applied to rats (Rattus norvegicus) trained in a water maze for 1, 3 or 5 days of training. Sustained changes throughout training were found in the lateral septal nucleus and anteroventral thalamic nucleus. As compared to naïve or habituation groups, rats with 1 day of training in the spatial learning task showed involvement of the lateral mammillary nucleus, basolateral amygdala and anterodorsal thalamic nucleus. By 5 days of training, there were mean changes in the hippocampal CA3 field and the prefrontal cortex. The regions involved and their pattern of network interactions changed progressively over days of training. At 1-day there was an open serial network of pairwise correlations. At 3-days there was a more closed reciprocal network of intercorrelations. At 5-days there were three separate parallel networks. In addition, brain-behavior correlations showed that CA1 and CA3 hippocampal fields together with the parietal cortex are related to the mastery of the spatial learning task. The present study extends previous findings on the progressive contribution of neural networks to spatial learning.     

Associative representational plasticity in the auditory cortex: a synthesis of two disciplines

Historically, sensory systems have been largely ignored as potential loci of information storage in the neurobiology of learning and memory. They continued to be relegated to the role of "sensory analyzers" despite consistent findings of associatively induced enhancement of responses in primary sensory cortices to behaviorally important signal stimuli, such as conditioned stimuli (CS), during classical conditioning. This disregard may have been promoted by the fact that the brain was interrogated using only one or two stimuli, e.g., a CS(+) sometimes with a CS(-), providing little insight into the specificity of neural plasticity. This review describes a novel approach that synthesizes the basic experimental designs of the experimental psychology of learning with that of sensory neurophysiology. By probing the brain with a large stimulus set before and after learning, this unified method has revealed that associative processes produce highly specific changes in the receptive fields of cells in the primary auditory cortex (A1). This associative representational plasticity (ARP) selectively facilitates responses to tonal CSs at the expense of other frequencies, producing tuning shifts toward and to the CS and expanded representation of CS frequencies in the tonotopic map of A1. ARPs have the major characteristics of associative memory: They are highly specific, discriminative, rapidly acquired, exhibit consolidation over hours and days, and can be retained indefinitely. Evidence to date suggests that ARPs encode the level of acquired behavioral importance of stimuli. The nucleus basalis cholinergic system is sufficient both for the induction of ARPs and the induction of specific auditory memory. Investigation of ARPs has attracted workers with diverse backgrounds, often resulting in behavioral approaches that yield data that are difficult to interpret. The advantages of studying associative representational plasticity are emphasized, as is the need for greater behavioral sophistication.     

Glucocorticoids enhance taste aversion memory via actions in the insular cortex and basolateral amygdala

It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function. Corticosterone (1.0 or 3.0 mg/kg) administered subcutaneously to male Sprague–Dawley rats immediately after the pairing of saccharin consumption with the visceral malaise-inducing agent lithium chloride (LiCl) dose-dependently increased aversion to the saccharin taste on a 96-h retention test trial. In a second experiment, rats received corticosterone either immediately after saccharin consumption or after the LiCl injection, when both stimuli were separated by a 3-h time interval, to investigate whether corticosterone enhances memory of the gustatory or visceral stimulus presentation. Consistent with the finding that the LiCl injection, but not saccharin consumption, increases endogenous corticosterone levels, corticosterone selectively enhanced CTA memory when administered after the LiCl injection. Suppression of this training-induced release of corticosterone with the synthesis-inhibitor metyrapone (35 mg/kg) impaired CTA memory, and was dose-dependently reversed by post-training supplementation of corticosterone. Moreover, direct post-training infusions of corticosterone into the insular cortex or basolateral complex of the amygdala, two brain regions that are critically involved in the acquisition and consolidation of CTA, also enhanced CTA retention, whereas post-training infusions into the dorsal hippocampus were ineffective. These findings provide evidence that glucocorticoid effects on memory consolidation are not limited to hippocampus-dependent spatial/contextual information, but that these hormones also modulate memory consolidation of discrete-cue associative learning via actions in other brain regions.     

Brain activity during the encoding, retention, and retrieval of stimulus representations

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.     

Human trace fear conditioning: right-lateralized cortical activity supports trace-interval processes

Pavlovian conditioning requires the convergence and simultaneous activation of neural circuitry that supports conditioned stimulus (CS) and unconditioned stimulus (US) processes. However, in trace conditioning, the CS and US are separated by a period of time called the trace interval, and thus do not overlap. Therefore, determining brain regions that support associative learning by maintaining a CS representation during the trace interval is an important issue for conditioning research. Prior functional magnetic resonance imaging (fMRI) research has identified brain regions that support trace-conditioning processes. However, relatively little is known about whether this activity is specific to the trace CS, the trace interval, or both periods of time. The present study was designed to disentangle the hemodynamic response produced by the trace CS from that associated with the trace interval, in order to identify learning-related activation during these distinct components of a trace-conditioning trial. Trace-conditioned activity was observed within dorsomedial prefrontal cortex (PFC), dorsolateral PFC, insula, inferior parietal lobule (IPL), and posterior cingulate (PCC). Each of these regions showed learning-related activity during the trace CS, while trace-interval activity was only observed within a subset of these areas (i.e., dorsomedial PFC, PCC, right dorsolateral PFC, right IPL, right superior/middle temporal gyrus, and bilateral insula). Trace-interval activity was greater in right than in left dorsolateral PFC, IPL, and superior/middle temporal gyrus. These findings indicate that components of the prefrontal, cingulate, insular, and parietal cortices support trace-interval processes, as well as suggesting that a right-lateralized fronto-parietal circuit may play a unique role in trace conditioning.