大鼠海马CA1区神经活动对体感刺激响应的研究

发布时间：2018-03-30 23:18

本文选题：体感刺激　切入点：海马　出处：《浙江大学》2014年博士论文

【摘要】：感觉信号的处理一直是神经科学领域研究的热点,体感感觉因其遍布全身的感受器以及在触摸技术领域的广泛应用越来越受到重视。海马作为学习和记忆的中枢结构,从内嗅皮质接收有关外界体感刺激的信号,并将其按某种模式编码,以便信息在大脑中的传播和储存。早先的研究发现体感刺激可以使海马CA1区的多单元放电活动(multiple unit activity, MUA)发生变化,但其对CA1区具体的作用效果和机制并不明确。由于对体感信息的处理与动物的生存和活动息息相关,因此研究体感信息在海马区中的信号响应和处理机制具有重要意义。本文通过对麻醉大鼠施加夹尾刺激,利用记录位点高密度分布的微电极阵列,记录海马CA1区的各种神经活动信号。主要研究了场电位、锋电位以及正向诱发电位对体感刺激的响应,考察了刺激对海马CA1区的作用效果；并且建立了包含体感输入和局部抑制回路的CA1区神经网络模型,利用计算机仿真验证了动物实验结果的产生机制；最后对海马中体感信息的处理与编码进行了探讨。本文的主要研究结果如下： (1)体感刺激对大鼠海马CA1区的主神经元活动具有抑制作用在夹尾的体感刺激作用下,CA1区的场电位变成以θ节律为主要功率成分,同时伴随有不一致的MUA响应(发放减少或者不变)；其中,锥体细胞的锋电位发放频率减小,中间神经元的发放频率增加；锥体细胞爆发式发放频率减小,每个爆发式发放所包含的锋电位数量无明显变化；Schaffer侧支上施加正向脉冲刺激所诱发的CA1区群峰电位的幅值显著减小；CA1区的MUA、锥体细胞的发放对重复体感刺激产生了适应性现象(adaptation)。这些结果表明体感刺激对海马CA1区,尤其是锥体细胞兴奋性有明显的抑制作用。 (2)数学模型的仿真结果表明体感刺激可以增强海马CA1区局部抑制性回路的作用利用NEURON软件建立CA1区神经网络模型,以研究海马对体感刺激响应的机制。模型的仿真结果与动物实验的结果一致,证明了体感刺激后CA1区锥体细胞兴奋性降低是中间神经元通过局部抑制回路作用的结果,其中前馈抑制回路和反馈抑制回路共同发挥作用,但以前馈抑制回路的作用为主导。为了进一步考察这种抑制作用是否能够用于控制异常的神经活动,我们还仿真了体感刺激对于过度兴奋状态下(癫痫发作时)锥体细胞兴奋性的影响,结果表明体感刺激可以减弱单侧颞叶癫痫活动,但无法减弱双侧颞叶癫痫活动。 (3)锋电位与场电位之间的相位锁定可能是CA1区编码体感信息的方式本文利用Rayleigh检验分析了神经元锋电位与场电位θ节律之间的时间相关性,揭示了一种可能的CA1区对体感信息编码的方式。研究结果表明：夹尾刺激前,少部分神经元(3/22)展现出与0节律周期相位锁定的特性；夹尾刺激作用下,呈现相位锁定特性的神经元数量显著增加(10/22),其锋电位发放集中在0节律周期的负相位附近。总之,本文结合了大鼠在体实验记录和建模仿真两种研究方法,考察了海马CA1区神经活动对体感刺激的响应,证明了体感刺激的抑制性作用,并且表明这种作用的内在机制是中间神经元通过局部抑制回路降低了锥体细胞的兴奋性。本文为海马是如何处理体感信息的研究提供了实验和理论依据,对海马的学习功能和神经编码的研究具有重要意义。
[Abstract]:Processing of sensory signals is always the research focus in the field of neuroscience, body sensation throughout the body because of its receptors as well as in touch technology widely used more and more attention. As the central structure of hippocampus in learning and memory, the received signal on the external cortical somatosensory stimulation from the entorhinal, and by a certain mode encoding, so that information is transmitted and stored in the brain. Previous studies found that somatosensory stimulation can make the multi unit discharge of hippocampal CA1 region (multiple unit, activity, MUA) change, but its CA1 region specific effects and mechanism is not clear. To deal with the animal because of somatosensory information. Life and activities, so the research has important significance to signal somatosensory information in the hippocampus in response and processing mechanism.
In this paper, by applying clamping tail stimulation in anesthetized rats, recorded by the microelectrode array site of high density distribution, various neural activity signals recorded in hippocampal CA1 region. The main research field potential, and a positive response of the spike evoked potentials on somatosensory stimulation, investigated the stimulation effect on the hippocampal CA1 region; and the establishment of the CA1 neural network model contains somatosensory input and local inhibitory circuits, which verified the mechanism of animal experiments using computer simulation; at the end of the processing and encoding somatosensory information in the hippocampus were discussed.
The main results of this paper are as follows:
(1) somatosensory stimulation inhibits the activity of main neurons in the CA1 region of the hippocampus of rats
In the tail clamp somatosensory stimulation, field potential CA1 region into a theta rhythm as the main power components, with inconsistent MUA response (payment is reduced or unchanged); among them, pyramidal cell spikes firing frequency decreases the firing frequency of interneurons increased; pyramidal cells burst firing frequency decreases each spike number type, the outbreak of issue contains no obvious change; positive pulse amplitude applied CA1 peaks potentials evoked by stimulation of the Schaffer collaterals significantly decreased; CA1 area MUA pyramidal cells release sense stimulate the adaptation of repeats (adaptation). These results suggest that somatosensory stimulation of the hippocampus CA1, especially can significantly inhibit the excitability of pyramidal cells.
(2) the simulation results of the mathematical model show that the somatosensory stimulation can enhance the role of the local inhibitory loop in the hippocampal CA1 region.
A CA1 neural network model by using NEURON software, to investigate the mechanism of hippocampal somatosensory stimulation response. The simulation results and the results of animal experiments, proved that somatosensory stimulation excited CA1 pyramidal cells is decreased as the result of interneurons by local inhibitory circuits, including feedforward inhibition and feedback loop together play the role of inhibitory loop, but with feedforward inhibitory circuits leading role. In order to further investigate whether this inhibition can be used to control the abnormal neuronal activity, we also simulated somatosensory stimulation for over excited state (seizure) affect the excitability of pyramidal cells. The results show that somatosensory stimulation can weaken unilateral temporal lobe epileptic activity, but not weaken the bilateral temporal lobe epilepsy.
(3) the phase locking between the front potential and the field potential may be the way of encoding the body sense information in the CA1 region.
This paper uses the Rayleigh test to analyze the time correlation between spikes and field potentials of the theta rhythm, reveals the way of somatosensory information encoding a putative CA1 region. The results show that: the tail clipping before stimulation, a few neurons (3/22) show the characteristics of 0 phase locking and rhythm cycle; stimulate tail under the action of the number of neurons showed phase locking characteristics significantly increased (10/22), the spike potentials are concentrated in the vicinity of the negative phase 0 rhythm cycle.
In conclusion, this paper combines the rat in vivo recording and modeling and Simulation of two kinds of research methods, investigated the response of neural activity in hippocampal CA1 area of somatosensory stimulation, that somatosensory stimulation of inhibitory effect, and indicates the inherent mechanism of the role of the interneurons reduces excitability of pyramidal cells by local inhibitory circuits this is how to deal with the hippocampus. Study on somatosensory information provides experimental and theoretical basis, it is important to study on hippocampal learning function and neural encoding.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：TN911.7

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