小腦在豚鼠延遲性和痕跡性條件眨眼反應(yīng)習(xí)得和表達過程中的作用研究
發(fā)布時間：2018-08-03 11:14
【摘要】： 目的和方法 長期以來人們一直認為小腦只具有運動調(diào)節(jié)功能,但實驗和臨床研究的結(jié)果表明小腦可能還參與了多種復(fù)雜的認知和學(xué)習(xí)過程,如運動性學(xué)習(xí)。 經(jīng)典眨眼條件反射是研究小腦參與運動性學(xué)習(xí)機制的極好模型。該類條件反射的建立依賴于條件刺激和非條件刺激的配對出現(xiàn)。根據(jù)條件刺激與非條件刺激出現(xiàn)時間的不同,經(jīng)典眨眼條件反射可以分成延遲性和痕跡性兩種模式。在前者中,條件刺激先于非條件刺激開始,并與非條件刺激同時結(jié)束。而在后者中,條件刺激結(jié)束與非條件刺激開始之間存在一個時間間隔。 大量實驗研究(包括損毀、神經(jīng)元單位放電記錄、刺激、可逆性失活和腦功能性成像技術(shù)等)的結(jié)果均提示小腦是延遲性眨眼條件反射建立所必需的神經(jīng)結(jié)構(gòu)。但是,對小腦皮層和小腦中位核在此過程中的相對重要性仍存在較大的爭議。此外,近期的研究發(fā)現(xiàn),小腦皮層和小腦中位核在痕跡性眨眼條件反射過程中均有不同程度的活化,但它們在此過程中的作用仍不清楚。 本研究的目的就是:(1)利用化學(xué)性可逆性失活的方法,在延遲性和痕跡性條件反射訓(xùn)練過程中失活小腦的中位核,觀察失活作用對眨眼條件反射習(xí)得的影響,近而判斷小腦中位核在延遲性和痕跡性眨眼條件反射建立過程中的作用;(2)利用透射電鏡技術(shù),檢測延遲性和痕跡性眨眼條件反射建立后小腦中位核內(nèi)突觸超微結(jié)構(gòu)的變化,初步探討小腦中位核參與兩類眨眼條件反射建立的機制(;3)利用化學(xué)性受體阻斷法,阻斷小腦皮層對小腦中位核神經(jīng)元活動的影響,近而判斷小腦皮層在痕跡性條件眨眼反應(yīng)表達控制過程中的作用。研究小腦在延遲性和痕跡性條件眨眼反應(yīng)習(xí)得和表達過程中的作用,既能全面確定小腦的運動性學(xué)習(xí)功能,又能為深入地研究相關(guān)機制提供新思路,具有重要的理論意義。 結(jié)果 1.單側(cè)小腦中位核在延遲性條件眨眼反應(yīng)習(xí)得過程中的作用 1)豚鼠經(jīng)典眨眼條件反射建立的關(guān)鍵期為條件反射訓(xùn)練第2-4天; 2) 2.50μg/kg劑量的蠅蕈醇可以完全抑制一側(cè)的豚鼠小腦中位核; 3)訓(xùn)練前向左側(cè)小腦中部定量微注射GABAA受體激動劑蠅蕈醇,可逆性失活左側(cè)小腦中位核,可以完全抑制豚鼠左側(cè)延遲性眨眼條件反射的習(xí)得; 4)訓(xùn)練前向右側(cè)小腦中部定量微注射GABAA受體激動劑蠅蕈醇,可逆性失活右側(cè)小腦中位核,對豚鼠左側(cè)延遲性眨眼條件反射習(xí)得的早期階段具有顯著的遲滯效應(yīng),但這種遲滯效應(yīng)在豚鼠左側(cè)延遲性眨眼條件反射習(xí)得的后期不再顯著; 5)向小腦中部微注射無論是蠅蕈醇還是人工腦脊液均不會顯著影響非條件眨眼反應(yīng)的表達。 2.小腦中位核在痕跡性條件眨眼反應(yīng)習(xí)得過程中的作用 1)在痕跡性眨眼條件反射訓(xùn)練期間,可逆性失活一側(cè)小腦中位核,可以阻止豚鼠對刺激間隔期為50 ms的同側(cè)痕跡性眨眼條件反射習(xí)得,但卻不能阻止豚鼠對刺激間隔期為250 ms的同側(cè)痕跡性眨眼條件反射習(xí)得; 2)當痕跡性眨眼條件反應(yīng)已經(jīng)習(xí)得后,無論刺激間隔期的長度如何,可逆性失活一側(cè)小腦中位核,均可以顯著抑制已習(xí)得的同側(cè)痕跡性條件眨眼反應(yīng)表達; 3.經(jīng)典眨眼條件反射習(xí)得后豚鼠小腦中位核內(nèi)突觸超微結(jié)構(gòu)的變化 1)延遲性模式配對訓(xùn)練組豚鼠小腦中位核內(nèi)興奮性和抑制性突觸后膜致密物均顯著增厚; 2)痕跡性模式配對和非配對訓(xùn)練都未顯著改變豚鼠訓(xùn)練側(cè)小腦中位核內(nèi)突觸的超微結(jié)構(gòu); 4.小腦皮層在痕跡性條件眨眼反應(yīng)表達過程中的作用 1)當建立穩(wěn)定的痕跡性眨眼條件反射后,向小腦中部微注射GABAA受體拮抗劑甲酰荷包牡丹堿,封閉小腦中位核神經(jīng)元表面GABAA受體,可以顯著地改變豚鼠已習(xí)得的痕跡性條件眨眼反應(yīng)的拓撲學(xué)特征; 2)當建立穩(wěn)定的痕跡性眨眼條件反射后,向小腦中部微注射GABAA受體激動劑蠅蕈醇使小腦中位核神經(jīng)元細胞膜電位超極化,抑制中位核神經(jīng)元活動,可以完全地抑制豚鼠對已習(xí)得痕跡性條件眨眼反應(yīng)的表達。 結(jié)論 1.同側(cè)小腦中位核在延遲性眨眼條件反射的建立過程中起到了至關(guān)重要的作用,而對側(cè)小腦中位核僅參與了該類眨眼條件反射習(xí)得的早期過程; 2.小腦中位核是否參與痕跡性眨眼條件反射的建立,取決于條件刺激與非條件刺激之間的時間間隔。隨著時間間隔長度的增加,小腦中位核在痕跡性眨眼條件反射建立過程中的重要性就越小。但是,無論刺激間隔的長短,小腦中位核均是痕跡性條件眨眼反應(yīng)表達所必需的神經(jīng)結(jié)構(gòu); 3.延遲性眨眼條件反射訓(xùn)練可以改變訓(xùn)練同側(cè)小腦中位核內(nèi)突觸的超微結(jié)構(gòu),但相同刺激參數(shù)的痕跡性眨眼條件反射訓(xùn)練并不引起訓(xùn)練同側(cè)小腦中位核內(nèi)突觸的超微結(jié)構(gòu)發(fā)生類似改變,提示小腦中位核可能并不參與痕跡性眨眼條件反射的建立過程; 4.小腦皮層可能參與了對痕跡性條件眨眼反應(yīng)拓撲學(xué)特征的控制過程。
[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.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2009
【分類號】：R33
本文編號：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.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2009
【分類號】：R33
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