中缝背核不同类型神经元在奖赏相关行为中活性的研究

发布时间：2018-02-23 05:01

本文关键词： 决策奖赏利用和奖赏寻觅状态中缝背核 5-HT GABA　出处：《北京协和医学院》2016年博士论文　论文类型：学位论文

【摘要】：原初奖赏对物种的生存至关重要。在基于奖赏的觅食决策行为中,动物的行为状态需要在奖赏利用状态和奖赏寻觅状态之间不断切换以获取更多的奖赏。中缝背核是前脑血清素(5-HT)的主要来源之一,它是异质性的核团,除了5-HT神经元,还包含γ-氨基丁酸(GABA)神经元等多种不同类型的神经元。中缝背核参与调节和控制奖赏相关的行为,处理奖赏相关的信息。迄今为止,中缝背核基因特异性的神经元的活性在动物摄取原初奖赏时怎样变化仍然不清楚。中缝背核神经元参与调节动物的行为状态,而前人尚未阐明中缝背核不同类型的神经元在动物处于奖赏利用状态或者奖赏寻觅状态下活性怎样变化。在此项研究中,我们利用神经元特异性的光纤记录和在体电生理记录研究了中缝背核5-HT和GABA神经元在动物摄取原初奖赏,以及动物处于奖赏利用状态和奖赏寻觅状态下的活性变化。利用光纤记录中缝背核5-HT神经元群体的钙信号活性变化,我们发现原初奖赏,包括食物、交配行为以及社会性的交往行为能够有效地激活中缝背核5-HT神经元,但是厌恶性的刺激比如苦味的奎宁水和足底电击并不能激活中缝背核5-HT神经元,甚至导致其活性的降低。正相反,我们发现中缝背核GABA神经元群体在动物摄取奖赏性的食物和蔗糖溶液时钙信号活性降低,但厌恶性的足底电击可以有效地激活中缝背核GABA神经元。在基于奖赏的觅食行为中,中缝背核5-HT神经元的活性在动物处于奖赏利用的行为状态时较高,而在动物处于奖赏寻觅状态时活性较低。奖赏利用状态可以细致分成奖赏期待和奖赏摄取阶段,光纤记录中缝背核5-HT神经元群体钙活性发现,在奖赏期待阶段5-HT神经元活性逐渐持续升高,并维持高活性状态直到奖赏的到来；奖赏摄取起始时,5-HT神经元钙活性进一步升高。在体电生理记录单个5-HT神经元活性进一步验证了光纤记录的结果,进一步发现典型的5-HT神经元在奖赏期待阶段被强直激活,而在奖赏摄取时成簇发放。同时,还存在其它的神经元发放类型。与5-HT神经元的活性大体相反,中缝背核GABA神经元在动物处于奖赏利用状态时呈现较低的活性,而在奖赏寻觅时呈现较高的活性。作为对照,腹侧被盖区DA神经元在奖赏决策行为中呈现出与5-HT神经元不同的活性特征。我们的研究暗示中缝背核5-HT神经元的激活可以促进动物奖赏利用行为状态但抑制奖赏寻觅的行为状态,而GABA神经元则相反。同时,揭示了5-HT以与DA神经元不同的方式参与编码奖赏信息。该研究为人们对5-HT相关的精神类疾病的机理的理解提供了坚实的数据基础。
[Abstract]:Primordial rewards are essential to the survival of species. In rewarding foraging decisions, Animal behavior needs to be switched between the reward utilization state and the reward seeking state to obtain more rewards. The dorsal raphe nucleus is one of the main sources of serotonin 5-HTs in the forebrain, and it is a heterogeneous nucleus with the exception of 5-HT neurons. The dorsal raphe nucleus is involved in the regulation and control of reward related behavior, processing of reward related information. It remains unclear how the activity of gene-specific neurons in the dorsal raphe nucleus changes when animals receive the original reward. Dorsal raphe nucleus neurons are involved in regulating animal behavior. However, it has not been clarified how the activity of the different types of neurons in the dorsal raphe nucleus changes when the animal is in the state of reward utilization or seeking the reward. We studied the primordial reward of 5-HT and GABA neurons in the dorsal raphe nucleus in animals using neuron specific optical fiber recording and in vivo electrophysiological recording. And the changes in the activity of animals in the state of reward utilization and reward seeking. Using optical fibers to record changes in calcium signal activity in the 5-HT neuron population in the dorsal raphe nucleus, we found that the primary reward, including food, Mating and social interaction can effectively activate 5-HT neurons in the dorsal raphe nucleus, but aversion stimuli such as bitter quinine water and plantar shock do not activate 5-HT neurons in the dorsal raphe nucleus. On the contrary, we found that GABA neurons in the dorsal raphe nucleus decreased their calcium signal activity when they ate reward food and sucrose solution. In reward based foraging behavior, the activity of 5-HT neurons in the dorsal raphe nucleus was higher when the animal was in the behavior of reward utilization. However, when animals were in the state of reward seeking, the activity was lower. The state of reward utilization could be divided into reward expectation stage and reward uptake stage. The calcium activity of 5-HT neurons in dorsal raphe nucleus was recorded by optical fiber. At the stage of expectation of reward, the activity of 5-HT neurons continued to increase and remained high until the arrival of reward. The calcium activity of 5-HT neurons increased further during the initiation of reward uptake. The activity of single 5-HT neurons recorded in vivo further verified the results of optical fiber recording, and it was further found that typical 5-HT neurons were strongly activated during the reward expectation stage. In contrast to the activity of 5-HT neurons, the GABA neurons in the dorsal raphe nucleus showed low activity when the animals were in the state of reward utilization. The reward was found to be more active. As a control, The DA neurons in ventral tegmental area show different activity characteristics from 5-HT neurons in reward decision making. Our study suggests that the activation of 5-HT neurons in dorsal raphe nucleus can promote animal reward to use behavioral state but inhibit reward. The state of seeking, GABA neurons, on the other hand, reveal that 5-HT encodes reward information in a different way from DA neurons. This study provides a solid data basis for understanding the mechanism of 5-HT related mental disorders.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q42

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