小脑在豚鼠延迟性和痕迹性条件眨眼反应习得和表达过程中的作用研究
发布时间：2018-08-03 11:14
【摘要】： 目的和方法 长期以来人们一直认为小脑只具有运动调节功能,但实验和临床研究的结果表明小脑可能还参与了多种复杂的认知和学习过程,如运动性学习。 经典眨眼条件反射是研究小脑参与运动性学习机制的极好模型。该类条件反射的建立依赖于条件刺激和非条件刺激的配对出现。根据条件刺激与非条件刺激出现时间的不同,经典眨眼条件反射可以分成延迟性和痕迹性两种模式。在前者中,条件刺激先于非条件刺激开始,并与非条件刺激同时结束。而在后者中,条件刺激结束与非条件刺激开始之间存在一个时间间隔。 大量实验研究(包括损毁、神经元单位放电记录、刺激、可逆性失活和脑功能性成像技术等)的结果均提示小脑是延迟性眨眼条件反射建立所必需的神经结构。但是,对小脑皮层和小脑中位核在此过程中的相对重要性仍存在较大的争议。此外,近期的研究发现,小脑皮层和小脑中位核在痕迹性眨眼条件反射过程中均有不同程度的活化,但它们在此过程中的作用仍不清楚。 本研究的目的就是:(1)利用化学性可逆性失活的方法,在延迟性和痕迹性条件反射训练过程中失活小脑的中位核,观察失活作用对眨眼条件反射习得的影响,近而判断小脑中位核在延迟性和痕迹性眨眼条件反射建立过程中的作用;(2)利用透射电镜技术,检测延迟性和痕迹性眨眼条件反射建立后小脑中位核内突触超微结构的变化,初步探讨小脑中位核参与两类眨眼条件反射建立的机制(;3)利用化学性受体阻断法,阻断小脑皮层对小脑中位核神经元活动的影响,近而判断小脑皮层在痕迹性条件眨眼反应表达控制过程中的作用。研究小脑在延迟性和痕迹性条件眨眼反应习得和表达过程中的作用,既能全面确定小脑的运动性学习功能,又能为深入地研究相关机制提供新思路,具有重要的理论意义。 结果 1.单侧小脑中位核在延迟性条件眨眼反应习得过程中的作用 1)豚鼠经典眨眼条件反射建立的关键期为条件反射训练第2-4天; 2) 2.50μg/kg剂量的蝇蕈醇可以完全抑制一侧的豚鼠小脑中位核; 3)训练前向左侧小脑中部定量微注射GABAA受体激动剂蝇蕈醇,可逆性失活左侧小脑中位核,可以完全抑制豚鼠左侧延迟性眨眼条件反射的习得; 4)训练前向右侧小脑中部定量微注射GABAA受体激动剂蝇蕈醇,可逆性失活右侧小脑中位核,对豚鼠左侧延迟性眨眼条件反射习得的早期阶段具有显著的迟滞效应,但这种迟滞效应在豚鼠左侧延迟性眨眼条件反射习得的后期不再显著; 5)向小脑中部微注射无论是蝇蕈醇还是人工脑脊液均不会显著影响非条件眨眼反应的表达。 2.小脑中位核在痕迹性条件眨眼反应习得过程中的作用 1)在痕迹性眨眼条件反射训练期间,可逆性失活一侧小脑中位核,可以阻止豚鼠对刺激间隔期为50 ms的同侧痕迹性眨眼条件反射习得,但却不能阻止豚鼠对刺激间隔期为250 ms的同侧痕迹性眨眼条件反射习得; 2)当痕迹性眨眼条件反应已经习得后,无论刺激间隔期的长度如何,可逆性失活一侧小脑中位核,均可以显著抑制已习得的同侧痕迹性条件眨眼反应表达; 3.经典眨眼条件反射习得后豚鼠小脑中位核内突触超微结构的变化 1)延迟性模式配对训练组豚鼠小脑中位核内兴奋性和抑制性突触后膜致密物均显著增厚; 2)痕迹性模式配对和非配对训练都未显著改变豚鼠训练侧小脑中位核内突触的超微结构; 4.小脑皮层在痕迹性条件眨眼反应表达过程中的作用 1)当建立稳定的痕迹性眨眼条件反射后,向小脑中部微注射GABAA受体拮抗剂甲酰荷包牡丹碱,封闭小脑中位核神经元表面GABAA受体,可以显著地改变豚鼠已习得的痕迹性条件眨眼反应的拓扑学特征; 2)当建立稳定的痕迹性眨眼条件反射后,向小脑中部微注射GABAA受体激动剂蝇蕈醇使小脑中位核神经元细胞膜电位超极化,抑制中位核神经元活动,可以完全地抑制豚鼠对已习得痕迹性条件眨眼反应的表达。 结论 1.同侧小脑中位核在延迟性眨眼条件反射的建立过程中起到了至关重要的作用,而对侧小脑中位核仅参与了该类眨眼条件反射习得的早期过程; 2.小脑中位核是否参与痕迹性眨眼条件反射的建立,取决于条件刺激与非条件刺激之间的时间间隔。随着时间间隔长度的增加,小脑中位核在痕迹性眨眼条件反射建立过程中的重要性就越小。但是,无论刺激间隔的长短,小脑中位核均是痕迹性条件眨眼反应表达所必需的神经结构; 3.延迟性眨眼条件反射训练可以改变训练同侧小脑中位核内突触的超微结构,但相同刺激参数的痕迹性眨眼条件反射训练并不引起训练同侧小脑中位核内突触的超微结构发生类似改变,提示小脑中位核可能并不参与痕迹性眨眼条件反射的建立过程; 4.小脑皮层可能参与了对痕迹性条件眨眼反应拓扑学特征的控制过程。
[Abstract]:Purpose and method
The cerebellum has long been thought to have only exercise regulation, but the results of experimental and clinical studies suggest that the cerebellum may also be involved in a variety of complex cognitive and learning processes, such as sports learning.
Classical blinking conditioning is an excellent model for the study of the mechanism of the cerebellum to participate in sports learning. The establishment of this kind of conditioned reflex depends on the pairing of conditioned stimulus and unconditioned stimulus. The classical blink reflex can be divided into two modes of delay and trace according to the time of the conditioned stimulus and the unconditioned stimulus. In the latter, the conditioned stimulus begins at the beginning of the unconditioned stimulus and ends with the unconditioned stimulus at the same time. In the latter, there is a time interval between the end of the conditioned stimulus and the beginning of the unconditioned stimulus.
A large number of experimental studies (including damage, neuronal unit discharge recording, stimulation, reversible inactivation, and brain functional imaging) suggest that the cerebellum is the necessary neural structure for the establishment of delayed blinking conditioning. However, the relative importance of the cerebellar cortex and cerebellar nucleus in this process is still controversial. In addition, recent studies have found that the nucleus of the cerebellar cortex and cerebellum have varying degrees of activation during the process of trace blink reflex, but their role in the process is still unclear.
The purpose of this study is: (1) the effect of inactivation on the acquisition of blink conditioned reflex is observed by using chemical reversible inactivation in delayed and trace conditioned reflex training, and the effect of inactivation on the acquisition of blinking reflex is observed, and the role of the cerebellar nucleus in the establishment of delayed and trace blink reflex is determined; (2) The changes of synaptic ultrastructure in the middle cerebellar nucleus were detected by transmission electron microscopy, and the mechanism of the involvement of the cerebellar nucleus in the establishment of two types of blink reflex was preliminarily investigated. (3) the effects of the cerebral cortex on the neuronal activity of the cerebellar nucleus were blocked by the chemical receptor blocking method. The role of the cerebellar cortex in the process of the expression control of the marked conditioned blink reaction. The study of the role of the cerebellum in the acquisition and expression of the delayed and trace condition blink reaction in the cerebellum can not only fully determine the motor learning function of the cerebellum, but also provide new ideas for the in-depth study of the related mechanism, which has important theoretical significance.
Result
1. the role of unilateral cerebellar median nucleus in the acquisition of delayed conditioned blink reaction.
1) the critical period for the establishment of classical blink conditioned reflex in guinea pigs was conditioned reflex training on the 2-4 day.
2) 2.50 g/kg dose of muscarol inhibited the cerebellar median nucleus in one guinea pig completely.
3) the quantitative microinjection of GABAA receptor agonist to the left cerebellum before training, and the reversible inactivation of the middle cerebellar nucleus in the left cerebellum, can completely inhibit the acquisition of delayed blinking reflex in the left side of the guinea pig.
4) the quantitative microinjection of the GABAA receptor agonist to the right cerebellum before training, and the reversible inactivation of the right cerebellar nucleus in the right cerebellum, had a significant lag effect on the early stage of the delayed blinking acquisition of the left side of the guinea pig, but this lag effect was no longer significant at the later stage of delayed blinking acquisition in the left side of the guinea pig.
5) microinjection of either cerebellum or artificial cerebrospinal fluid into cerebellum does not significantly affect the expression of unconditioned blink response.
2. the role of cerebellar median nucleus in the acquisition of trace conditional blink response.
1) the reversible inactivation of the median cerebellar nucleus during the training of the trace blinking reflex could prevent the guinea pig's acquisition of the imprinted blinking acquisition of the same side of the stimulus interval of 50 ms, but it did not prevent the guinea pig's acquisition of the imprinted blink of the same lateral blink by 250 ms at the interval of stimulation.
2) after the acquisition of the trace blink condition response, no matter the length of the stimulation interval, the reversible inactivation of the median nucleus of the cerebellum could significantly inhibit the acquired expression of the acquired blink reaction.
3. changes in synaptic ultrastructure in the cerebellar median nucleus after learning from classical blink conditioning.
1) in the delayed mode matching training group, the excitatory and inhibitory postsynaptic membrane compacts in the cerebellar median nuclei of guinea pigs were significantly thickened.
2) trace pattern matching and unpaired training did not significantly alter the ultrastructure of synapses in the cerebellar median nucleus on the training side of guinea pigs.
4. the role of cerebellar cortex in the expression of trace conditional blink response.
1) after establishing a stable trace blink reflex, microinjection of the GABAA receptor antagonist, formylonine to the middle of the cerebellum, closed the GABAA receptor on the surface of the cerebellar nucleus neurons, which could significantly change the topological characteristics of the acquired blink reaction in the guinea pig.
2) after the establishment of a stable trace blink reflex, microinjection of the GABAA receptor agonist to the middle of the cerebellum caused the hyperpolarization of the membrane potential of the nucleus nucleus of the cerebellum to inhibit the activity of the nucleus neurons, which could completely inhibit the expression of the acquired blink reaction in the acquired condition of the guinea pig.
conclusion
1. the central nucleus of the ipsilateral cerebellum plays a vital role in the establishment of delayed blinking conditioning, while the nucleus of the contralateral cerebellum only participates in the early process of the acquisition of this kind of blinking.
2. whether the median nucleus of the cerebellum is involved in the establishment of a trace blink conditioned reflex depends on the time interval between the conditioned stimulus and the unconditioned stimulus. As the length of the time increases, the importance of the nucleus of the cerebellum is smaller in the process of establishing a trace blink conditioned reflex. However, the median nucleus of the cerebellum is all the nucleus of the cerebellum, regardless of the length of the stimulus interval. The neural structure required for the expression of blinking reaction.
3. delayed blinking conditioned reflex training can change the ultrastructure of synapses in the middle cerebellar nucleus of the cerebellum, but the same stimulus parameter's trace blink conditioning training does not cause similar changes in the ultrastructure of the synapse in the middle cerebellar nucleus, suggesting that the middle cerebellar nucleus may not be involved in the trace blink condition. The process of setting up reflection;
4. cerebellar cortex may play a role in controlling the topological characteristics of trace conditional blink reaction.
【学位授予单位】：第三军医大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R33
本文编号：2161570
[Abstract]:Purpose and method
The cerebellum has long been thought to have only exercise regulation, but the results of experimental and clinical studies suggest that the cerebellum may also be involved in a variety of complex cognitive and learning processes, such as sports learning.
Classical blinking conditioning is an excellent model for the study of the mechanism of the cerebellum to participate in sports learning. The establishment of this kind of conditioned reflex depends on the pairing of conditioned stimulus and unconditioned stimulus. The classical blink reflex can be divided into two modes of delay and trace according to the time of the conditioned stimulus and the unconditioned stimulus. In the latter, the conditioned stimulus begins at the beginning of the unconditioned stimulus and ends with the unconditioned stimulus at the same time. In the latter, there is a time interval between the end of the conditioned stimulus and the beginning of the unconditioned stimulus.
A large number of experimental studies (including damage, neuronal unit discharge recording, stimulation, reversible inactivation, and brain functional imaging) suggest that the cerebellum is the necessary neural structure for the establishment of delayed blinking conditioning. However, the relative importance of the cerebellar cortex and cerebellar nucleus in this process is still controversial. In addition, recent studies have found that the nucleus of the cerebellar cortex and cerebellum have varying degrees of activation during the process of trace blink reflex, but their role in the process is still unclear.
The purpose of this study is: (1) the effect of inactivation on the acquisition of blink conditioned reflex is observed by using chemical reversible inactivation in delayed and trace conditioned reflex training, and the effect of inactivation on the acquisition of blinking reflex is observed, and the role of the cerebellar nucleus in the establishment of delayed and trace blink reflex is determined; (2) The changes of synaptic ultrastructure in the middle cerebellar nucleus were detected by transmission electron microscopy, and the mechanism of the involvement of the cerebellar nucleus in the establishment of two types of blink reflex was preliminarily investigated. (3) the effects of the cerebral cortex on the neuronal activity of the cerebellar nucleus were blocked by the chemical receptor blocking method. The role of the cerebellar cortex in the process of the expression control of the marked conditioned blink reaction. The study of the role of the cerebellum in the acquisition and expression of the delayed and trace condition blink reaction in the cerebellum can not only fully determine the motor learning function of the cerebellum, but also provide new ideas for the in-depth study of the related mechanism, which has important theoretical significance.
Result
1. the role of unilateral cerebellar median nucleus in the acquisition of delayed conditioned blink reaction.
1) the critical period for the establishment of classical blink conditioned reflex in guinea pigs was conditioned reflex training on the 2-4 day.
2) 2.50 g/kg dose of muscarol inhibited the cerebellar median nucleus in one guinea pig completely.
3) the quantitative microinjection of GABAA receptor agonist to the left cerebellum before training, and the reversible inactivation of the middle cerebellar nucleus in the left cerebellum, can completely inhibit the acquisition of delayed blinking reflex in the left side of the guinea pig.
4) the quantitative microinjection of the GABAA receptor agonist to the right cerebellum before training, and the reversible inactivation of the right cerebellar nucleus in the right cerebellum, had a significant lag effect on the early stage of the delayed blinking acquisition of the left side of the guinea pig, but this lag effect was no longer significant at the later stage of delayed blinking acquisition in the left side of the guinea pig.
5) microinjection of either cerebellum or artificial cerebrospinal fluid into cerebellum does not significantly affect the expression of unconditioned blink response.
2. the role of cerebellar median nucleus in the acquisition of trace conditional blink response.
1) the reversible inactivation of the median cerebellar nucleus during the training of the trace blinking reflex could prevent the guinea pig's acquisition of the imprinted blinking acquisition of the same side of the stimulus interval of 50 ms, but it did not prevent the guinea pig's acquisition of the imprinted blink of the same lateral blink by 250 ms at the interval of stimulation.
2) after the acquisition of the trace blink condition response, no matter the length of the stimulation interval, the reversible inactivation of the median nucleus of the cerebellum could significantly inhibit the acquired expression of the acquired blink reaction.
3. changes in synaptic ultrastructure in the cerebellar median nucleus after learning from classical blink conditioning.
1) in the delayed mode matching training group, the excitatory and inhibitory postsynaptic membrane compacts in the cerebellar median nuclei of guinea pigs were significantly thickened.
2) trace pattern matching and unpaired training did not significantly alter the ultrastructure of synapses in the cerebellar median nucleus on the training side of guinea pigs.
4. the role of cerebellar cortex in the expression of trace conditional blink response.
1) after establishing a stable trace blink reflex, microinjection of the GABAA receptor antagonist, formylonine to the middle of the cerebellum, closed the GABAA receptor on the surface of the cerebellar nucleus neurons, which could significantly change the topological characteristics of the acquired blink reaction in the guinea pig.
2) after the establishment of a stable trace blink reflex, microinjection of the GABAA receptor agonist to the middle of the cerebellum caused the hyperpolarization of the membrane potential of the nucleus nucleus of the cerebellum to inhibit the activity of the nucleus neurons, which could completely inhibit the expression of the acquired blink reaction in the acquired condition of the guinea pig.
conclusion
1. the central nucleus of the ipsilateral cerebellum plays a vital role in the establishment of delayed blinking conditioning, while the nucleus of the contralateral cerebellum only participates in the early process of the acquisition of this kind of blinking.
2. whether the median nucleus of the cerebellum is involved in the establishment of a trace blink conditioned reflex depends on the time interval between the conditioned stimulus and the unconditioned stimulus. As the length of the time increases, the importance of the nucleus of the cerebellum is smaller in the process of establishing a trace blink conditioned reflex. However, the median nucleus of the cerebellum is all the nucleus of the cerebellum, regardless of the length of the stimulus interval. The neural structure required for the expression of blinking reaction.
3. delayed blinking conditioned reflex training can change the ultrastructure of synapses in the middle cerebellar nucleus of the cerebellum, but the same stimulus parameter's trace blink conditioning training does not cause similar changes in the ultrastructure of the synapse in the middle cerebellar nucleus, suggesting that the middle cerebellar nucleus may not be involved in the trace blink condition. The process of setting up reflection;
4. cerebellar cortex may play a role in controlling the topological characteristics of trace conditional blink reaction.
【学位授予单位】：第三军医大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R33
【参考文献】
相关期刊论文 前4条
1 隋建峰,高洁,罗峻,甘平,鲜晓东,黄扬帆;适用于低等哺乳动物的视听分辨行为自动训练系统[J];第三军医大学学报;2005年01期
2 林曦;胡波;万子兵;杨丽;黄率帅;隋建峰;;一种简易的豚鼠眨眼反应测量方法[J];第三军医大学学报;2008年24期
3 胡波;林曦;熊雁;黄维;刘国龙;隋建峰;;豚鼠齿状回颗粒细胞在追踪性眨眼条件反应巩固过程中的活动(英文)[J];生物化学与生物物理进展;2006年11期
4 ;A comparison of the spontaneous firing patterns between principal cells and fast spiking interneurons from dentate gyrus in waking guinea pigs[J];Neuroscience Bulletin;2006年01期
，本文编号：2161570
本文链接：https://www.wllwen.com/yixuelunwen/shiyanyixue/2161570.html
最近更新
教材专著
