上丘-丘脑外侧后核神经环路在处理本能恐惧反应中的作用研究

发布时间：2018-01-09 02:13

本文关键词：上丘-丘脑外侧后核神经环路在处理本能恐惧反应中的作用研究　出处：《中国科学院深圳先进技术研究院》2016年硕士论文　论文类型：学位论文

【摘要】：动物能对逐渐靠近自己的视觉危险刺激做出本能快速的防御性反应,行为学上主要表现为冻结和逃跑。依据本实验室前期的工作发现,小鼠对这种特定视觉刺激产生的本能恐惧行为,是通过上丘(superior colliculus,SC)、丘脑外侧后核(lateral posterior nucleus of thalamus,LP)到杏仁核这条快速的皮层下通路来介导。基于这些研究基础,我们希望理解的问题是:1)特定的、可以诱发本能恐惧行为的视觉输入信息在SC中编码后,这些视觉输入中的危险信息成分如何在SC到LP的通路中被抽提和加工;2)LP接受SC信息输入的功能亚区和神经元发放的特征。本研究以小鼠为实验对象,利用多种技术手段,包括本能恐惧行为检测、免疫组化分析、光遗传神经调控技术、在体多通道电生理记录以及在体光纤荧光信号检测等技术,对上述问题进行了研究。初步结果发现:1)用不同频率光刺激模拟不同强度的视觉刺激输入到上丘中层内侧(medial region of the intermediate layers of the SC,ILSCm)兴奋性神经元,能诱导小鼠产生防御性逃跑或冻结反应。而随着刺激频率的增加,小鼠的行为逐渐从冻结趋向于逃跑行为。因此,ILSCm兴奋性神经元活动的强弱在小鼠不同本能防御行为编码中起着很重要的作用。2)光遗传学激活SC到LP不同亚区的投射通路,发现刺激LPMR(mediorostral of lateral posterior thalamic nucleus)和LPMC/LPLR(mediocaudal or laterorostral of lateral posterior thalamic nucleus)亚区都能诱发小鼠产生冻结行为,但是LPMC/LPLR诱发冻结的时间更长,因此这提示LPMC/LPLR可能是接受上丘威胁刺激信号的主要功能亚区。为了验证这一假设,我们利用在体多通道电生理和光纤荧光检测技术,记录了looming刺激下LP不同亚区神经元的活动,结果发现LPLR对looming刺激没有反应而LPMR和LPMC则有,并且LPMC神经元活动与looming刺激诱导的防御行为具有相关性。因此,LPMC可能是接受上丘威胁信号的主要功能亚区。本文研究了SC和LP神经通路如何编码looming刺激引起的本能防御反应,进一步揭示了这条非经典的皮层下通路在对本能恐惧情感处理中的作用机制,这将为临床上开发治疗与恐惧异常类相关精神疾病提供新的思路和参考。
[Abstract]:Animals are able to react instinctively and defensively to visual hazard stimuli gradually approaching themselves, primarily in the form of freezes and escapes, according to previous work in our laboratory. The instinctive fear of this particular visual stimulus in mice is through the superior colliculus colliculus (SCS). Lateral posterior nucleus of thalamus. LP) is mediated by the rapid subcortical pathway to the amygdala. Based on these studies, the question we want to understand is: 1) specific. After the visual input information which can induce instinctive fear behavior is encoded in SC, how can the dangerous information components of these visual inputs be extracted and processed in the pathway from SC to LP; 2the functional subregion of SC information input and the characteristics of neuronal release were accepted by LP. In this study, mice were used as experimental subjects, using a variety of technical means, including instinctive fear behavior detection, immunohistochemical analysis. Photogenetic neural regulation technology, in vivo multi-channel electrophysiological recording and in vivo optical fiber fluorescence signal detection technology. The preliminary results show that different frequency of light stimulation is used to simulate visual stimulation of different intensity into the medial medial medial colliculus. Medial region of the intermediate layers of the SC. ILSCm) excitatory neurons can induce defensive escape or freeze response in mice. With the increase of stimulation frequency, the behavior of mice gradually changes from freezing to escaping. The activity of ILSCm excitatory neurons plays an important role in the encoding of different instinctive defense behaviors in mice. 2) photogenetics activates the projection pathway from SC to different subregions of LP. LPMR(mediorostral of lateral posterior thalamic nucleus. And LPMC / LPLR (. Mediocaudal or laterorostral of lateral posterior thalamic nucleus. All the subregions could induce freezing behavior in mice. But LPMC/LPLR induces freezing for longer, which suggests that LPMC/LPLR may be the main functional subregion that receives the superior colliculus threat stimuli. We recorded the activity of neurons in different subregions of LP stimulated by looming using in vivo multichannel electrophysiology and fiber-optic fluorescence detection techniques. The results showed that LPLR did not respond to looming stimulation, but LPMR and LPMC did. And the activity of LPMC neurons is related to the defense behavior induced by looming stimulation. LPMC may be the main functional subregion to receive the superior colliculus threat signal. We studied how SC and LP neural pathways encode the instinctive defense response induced by looming stimulation. It further reveals the mechanism of this nonclassical subcortical pathway in the treatment of instinctive fear emotion, which will provide new ideas and references for clinical treatment of mental disorders associated with fear abnormality.
【学位授予单位】：中国科学院深圳先进技术研究院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：B842

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