NMDA受体在海马CA_3区习得性LTP保持中的作用

在大鼠明暗分辨学习的建立和巩固过程中,通过与记录电极一起慢性埋植于海马CA_3区的注药管微量注射NMDA受体的特异性拮抗剂2-amino-5-phosphonovaleric acid(APV),观察对海马CA_3区突触效应及与之相关的习得性行为的影响。结果如下:(1)在动物经训练PS峰幅值刚增大至最高水平后,即在习得性LTP刚好形成后,每实验单元先于CA_3区注射AFV 1μl(2mmol/L),然后在药物有效作用时间内再进行训练,则PS峰值不能随训练而保持在最高水平,相反经8个实验单元,PS峰值降至实验前水平;相应地动物的正确反应率不能随训练而巩固,反而下降至10％以下。(2)在动物习得性LTP已形成并经一单元训练PS保持在最高水平后,于每实验单元训练前注射APV 1μl(2mmol/L),PS峰值同样不会随训练而保持在最高水平,经14个实验单元注药和训练,PS峰值逐渐降至实验前水平,相应地动物行为的正确反应率也降至10％以下,习得性行为消退,不过其消退速度比前一情况的动物为慢,说明习得性LTP发展情况不同,APV的作用效率有差别。结果表明:NMDA受体在习得性LTP的巩固中起着重要作用。     

大鼠海马CA3区的习得性长时程突触增强

本实验应用慢性埋植电极技术以电生理学结合行为学的方法,观察大鼠条件性饮水反应的建立、消退和再建立过程中,其海马CA_3区突触效应的变化规律。以刺激内嗅区的穿通纤维(PP)诱发的单突触的群体锋电位(PS)及群体兴奋性突触后电位(EPSPs)为指标,经叠加处理分析,发现随着条件反应的建立,海马CA_3锥体细胞出现突触效应的长时程增强(LTP),它随行为反应的实验性消退而消退,而在随后再次建立条件反应时,又重新出现;且无论此LTP达最高水平还是它的完全消退均超前于条件性行为反应的水平。又在一个实验日训练作业结束时PS并未立即随之增大,在24h内它随时间而发展,但到第4小时已达最高水平,且条件反应率是与PS的水平相应的,对PS与EPSPs的斜率进行相关分析表明,PS的变化主要是突触传递功效的变化。上述结果表明,海马CA_3区随着行为训练有习得性LTP产生。从其发神变化特点及其与条件性行为的关系,提示此习得性LTP极其可能是本实验中学习和记忆的展经基础。     

6—OHDA损毁背NE束对大鼠齿状回习得性长时程增强的影响

本工作用6-OHDA损毁大鼠双侧背去甲肾上腺素束,其后在条件性饮水反应建立中检测齿状回(DG)的突触效应及条件反应的变化,以探查NE在习得性长时程增强形成中的作用。结果如下:双测背NE束注6-OHDA(12μg/4μl)后,DG的群体锋电位(PS)的峰幅值持续下降,注药后第6天下降至50±6.3％,第12天下降至28±6.5％。在第6-12天这段时间,每天给大鼠进行20次训练,经7d 140次训练,DG并无习得性LTP产生,条件性饮水反应也不能建立,这些结果提示DG的NE的正常水平对其习得性LTP的形成是必要的,并提示脑干的蓝斑核可能通过背NE束对海马DG的习得性LTP的形成起调制作用。     

噪声对幼年和老年大鼠海马CA_3区习得性长时程突触增强的影响

经强噪声重复暴露(96 dB,2h/d,25 d)后,幼年和老年大鼠在条件反应的建立和再建立过程中,其海马CA_3区习得性长时程突触增强(LTP)的发展均受到明显阻抑,相应地动物达到学会标准需更多的训练。但幼年鼠受阻抑的程度更为严重。对习得性LTP的消退则在幼年和老年大鼠均无明显影响。本研究从突触功能的可塑性方面揭示幼年功物特别容易受到强噪声重复暴露的危害,提示应重视环境噪声对人类婴幼儿脑功能的损害作用的研究。     

幼年和老年大鼠学习中海马CA_3区长时程突触增强的年龄特征

研究发现幼年和老年大鼠在条件性饮水反应的建立、消退和再建立过程中,海马CA_3区有习得性长时程突触增强(LTP)的形成、消退和再形成现象。在它的形成和再形成以及每实验日训练作业后习得性LTP的发展上,幼年鼠明显快于老年鼠,而习得性LTP的消退,在两组间无明显差异。这既表明海马CA_3区的习得性LTP具年龄特征,也为论证习得性LTP可能是学习和记忆的神经基础之一提供了新的证据。     

幼年和老年人鼠学习中海马CA[3]区长时程突触增强的年龄特征

研究发现幼年和老年大鼠在条件性饮水反应的建立、消退和再建立过程中,海马CA[3]区有习得性长时程突触增强（LTP）的形成、消退和再形成现象。在它们的形成和再形成以及每实验日训练作业后习得性LTP的发展上,幼年鼠明显快于老年鼠,而习得性LTP的消退,在两组间无明显差异。这既表明海马CA[3]区的习得性LTP具年龄特征,也为论证习得性LTP可能是学习和记忆的神经基础之一提供了新的证据。     

东莨菪碱,印防己毒素对习得性长时程突触增强的影响

在大鼠条件性饮水反应的建立、消退和再建立过程中,于海马 CA_3区记录电极部位微量注射 M-胆碱受体阻断剂东莨菪碱和 GABA 受体阻断剂印防已毒素,观察其对习得性长时程突触增强的影响。结果表明,东莨菪碱有明显的抑制作用,印防已毒素则有明显的易化作用,同时相应地影响条件性行为;并发现习得性长时程突触增强的发展与变化是超前于条件性行为的发展和改变的。上述结果为进一步论证习得性长时程突触增强可能是学习和记忆的神经基础之一提供了证据,并提示海马 CA_3区习得性长时程增强的产生与保持有胆碱受体与 GABA 受体参与。     

在饮水条件反射中大鼠海马CA3区突触效应的变化

我们的工作表明,大鼠在明暗辨别学习过程中海马齿状回有习得性长时程增强(Long-term potentiation,LTP)现象,又CA_3区在大鼠学习和记忆过程有重要作用。本实验观察大白鼠海马CA_3区锥体细胞在条件性饮水反应的建立、巩固和消退过程中其突触效应的变化规律,以进一步探讨习得性LTP的特性,及从突触水平探讨海马CA_3区在学习记忆功能中的作用。     

Ca2+及其信号转导途径与长时程增强的关系

Ca2 作为信号转导过程中的第二信使,参与机体的各种反应,尤其在神经突触可塑性方面,突触前后Ca2 浓度的变化发挥了重要的信息传递作用.Ca2 在长时程增强(long-term potentiation,LTP)过程中也发挥重要作用.它不仅是LTP产生的触发器,而且能通过激活下游的蛋白激酶、磷酸化ERK,以及活化即刻早期基因(IEGs)等促进基因转录和蛋白质合成,最终参与LTP的维持.     

神经元的突触可塑性与学习和记忆

大量研究表明,神经元的突触可塑性包括功能可塑性和结构可塑性,与学习和记忆密切相关.最近,在经过训练的动物海马区,记录到了学习诱导的长时程增强(long term potentiation,LTP),如果用激酶抑制剂阻断晚期LTP,就会使大鼠丧失训练形成的记忆.这些结果指出,LTP可能是形成记忆的分子基础.因此,进一步研究哺乳动物脑内突触可塑性的分子机制,对揭示学习和记忆的神经基础有重要意义.此外,在精神迟滞性疾病和神经退行性疾病患者脑内记录到异常的LTP,并发现神经元的树突棘数量减少,形态上产生畸变或萎缩,同时发现,产生突变的基因大多编码调节突触可塑性的信号通路蛋白,故突触可塑性研究也将促进精神和神经疾病的预防和治疗.综述了突触可塑性研究的最新进展,并展望了其发展前景.     

NMDA受体在海马CA3区习得性TP保持中的作用

The effect of microinjection of 2-amino-5-phosphonovaleric acid (APV), a selective NMDA receptor antagonist, into the rat hippocampal CA3 area on the synaptic efficacy and related conditioned behavior during the acquisition and consolidation of discrimination learning behavior was examined. The results showed: (1) After population spike (PS) amplitude had just increased to the maximum through training i.e. learning-dependent LTP had just formed, APV 1 microliter (2 mmol/L) was injected into CA3 area, then the rats were trained during the time of efficacy of the drug in every experimental block. The result demonstrated that the PS amplitude could not be maintained at the highest level but decreased to the pre-experiment level after 8 blocks. Correct response percentage of rats could not be consolidated with further training but decreased to less than 10%. (2) After the PS amplitude had kept up at the highest level, APV 1 microliter (2 mmol/L) was injected into CA3 area, then the rats were trained during the time of efficacy of the drug in every experimental block, in which case the PS amplitude also could not be maintained at the highest level but decreased to the pre-experiment level after 14 blocks. Correlatively, when the correct response percentage of rats decreased gradually to less than 10%, the conditioned response of the animals extinguished, but its extinction speed was slower than it was in result (1). These results suggest that the NMDA receptor in CA3 area plays an important role in the maintenance of the learning-dependent long-term potentiation.     

学习过程中MF－CA3与PP－CA3突触传递效应的变化

应用慢性电极埋植技术以电生理学结合行为学的方法,探查在学习过程中大鼠海马ＣＡ３区两种不同输入突触（ＭＦ－ＣＡ３突触和ＰＰ－ＣＡ３突触）的可塑性变化及其相互关系。结果如下：（１）在分辨反应的建立过程中,在ＣＡ３区由ＭＦ诱发（ＭＦ－ＣＡ３）的群体锋电位（ｐｏｐｕｌａｔｉｏｎｓｐｉｋｅ,ＰＳ）和由ＰＰ诱发（ＰＰ－ＣＡ３）的群体锋电位,两者的峰值同步增大,同步达最高水平,且ＰＳ峰值达最高水平先于行为反应达学会标准;（２）在自然消退过程中,两者的ＰＳ峰值也是同步恢复至训练前水平的。结果表明,在ＣＡ３区这两种输入突触的习得性ＬＴＰ的产生和消退都是同步的,提示了它们之间可能具有协同作用。     

The correction of the manifestations of a neurosis-like state in white rats by using the vitamin complex Aekol

Behavior of neurotized white rats was studied in two experimental situations: during training for passive and active avoidance of electroshock applied to the limbs and during testing the acquisition of the conditioned avoidance. It was shown that in behavior of rats in the neurosis-like state the signs of anxiety and fear dominated, the orienting-exploratory behavior was suppressed. The state correction was performed by per os introduction of the natural vitamin complex Aekol during the neurotization of animals.     

Importance of traces of a preceding unreinforced stimulus to the formation of inhibitory conditioned reflexes in the rat

The results of experiments with the inhibitory signal presented to rats after the positive one, showed the significance of the negative signal memory trace which interrupted alimentary behaviour and considerably accelerated its full extinction in response to the previously positive signal. Its significance is shown in experiments with amnesia produced by electroshock. According to the suggested concept negative conditioned reflexes are a result of formation of a temporary connection between memory traces of the negative conditioned signal and the non-reinforcement of this signal.     

Change in the signal properties of a conditioned stimulus during two-way avoidance conditioning in rats

Acquisition of two components of conditioned active avoidance behavior by rats was studied. First presentations of electroshock evoked a number of different behavioral reactions. However, after five trials many rats learned to escape punishment running away to another part of a shuttle-box. The efficiency of the avoidance reaction conditioning significantly depended on the ability of an animal to learn the correct escape reaction to the unconditioned stimulus. However, some animals were incapable for acquisition of the conditioned reaction despite their high level of successful escapes. Increase in the number of negative reactions to the conditioned stimulus (light) at the next stage of learning suggests that the conditioned stimulus becomes the signal of forthcoming punishment. The ability of an animal to identify the conditioned stimulus as a signal significantly affected the efficiency of conditioned avoidance acquisition.     

Long-term potentiation and unit evoked responses in the cingulate cortex of freely moving rats

Long-term potentiation (LTP) of synaptic efficacy is considered to be the most probable physiological mechanism of long-term memory. However, lack of understanding of cellular and subcellular mechanisms of LTP induction in freely behaving animals does not correspond to the importance of the problem. It was tested whether the characteristics of potentiation in the cingulate cortex after tetanization of the subiculocingulate tract (SCT) meet the criteria of true LTP (that passes all known stages in its development and lasts for more than a day in freely-behaving animals). Additionally, characteristics of spike responses to SCT stimulation and the effects of application of different glutamate receptor blockers were studied. Without application of GABA receptor blockers, the LTP lasted for more than 24 hours. Application of NMDA glutamate receptor blockers significantly inhibited field potentials evoke by testing stimulation. Short-latency spike responses to SCT stimulation were recorded with low probability that increased with stimulation intensity. The obtained data reveal the possibility to compare the involvement of cingulate neurons in acquisition of adaptive behavior and changes in their spike responses during the LTP development in freely-moving rats.     

Posttetanic Long-Term Potentiation in Rat Dentate Area Increases Postsynaptic 411B Immunoreactivity

411B is a monoclonal antibody raised to chick forebrain postsynaptic densities (PSDs) which also recognises an antigen in brain tissue from adult Wistar rats but not liver, heart, or lung. This antigen is enriched in the PSD fraction and appears to be a useful biochemical marker for plastic changes of postsynaptic structures in the rat brain. The aim of this study was to investigate whether 411B immunoreactivity is changed in various hippocampal subregions by post-tetanic long-term potentiation (LTP). LTP was elicited in freely moving rats by applying four trains of 300 square-wave pulses (frequency 200 Hz, pulse duration 0.2 ms, and intensity 300 mA) into the right perforant path; this included an increase in transmission efficacy at the ipsilateral perforant path-granular cell synapse of the dentate gyrus lasting several days. Eight hours after tetanisation, antigens recognised by monoclonal 411B and a polyclonal anti-actin antiserum were assayed in lysed homogenates of ipsi- and contralateral CA1. CA3, and CA4/dentate area hippocampal subfields as well as in visual cortex, cerebellum, and olfactory bulb dissected from LTP rats, and compared to passive controls. Under these experimental conditions, tetanisation of the perforant path resulted in a significant increase in the titre of 411B in the ipsilateral CA4/dentate area subfield (+34.0%; p less than 0.001) compared with passive controls, whereas in all other brain regions studied no differences between experimental and control rats were observed. In no region were anti-actin titres significantly different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)