The neural mechanisms involved in behavioral responses related to emotions

涉及情绪相关行为反应的神经机制

• 批准号: RGPIN-2017-06131
• 负责人: Proulx, Christophe
• 金额: $ 4.37万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763645
• 关键词: neural; mechanisms; involved; behavioral; responses

One of the most conspicuous characteristics of any organism is its ability to react to salient stimuli with an appropriate behavioral response that maximizes survival and minimizes threatening or unpleasant events. In mammals, emotions are considered as an evolutionary strategy to detect changes from the environment to direct proper behavioral responses. Emotions are generated by the complex interaction of interconnected brain structures part of the limbic system. The dorsal raphe nucleus (DRN), the main serotonergic nucleus of the brain, receives signals from different nuclei of the limbic system and in return regulates emotions and behavioral responses by releasing the neuromodulator serotonin (5-HT) in different parts of the central nervous system. Experimental results suggest that the 5-HT would be important to process aversive signals that are important to orchestrate behaviors when something aversive is expected. However, the mechanisms by which 5-HT controls emotions and behaviors is still elusive. This can be explained by the technical difficulties in specifically measuring and controlling serotonergic pathways in vivo.In this research proposal, we use innovative optogenetic and photometric approaches that will allow us to dissect the serotonergic circuitry involved in the processing of emotions. By using several behavioral tests commonly used in mice, we can correlate neural activity and behaviors. Using innovative optogenetic manipulation, we can also artificially activate or inhibit specific neural pathways and see how these manipulations can change behavioral responses. Specifically, in this program, we are interested in understanding how the lateral habenula (LHb) controls the activity of the main serotonergic center of the brain, the dorsal raphe nucleus (DRN). The LHb has been suggested to be the main disappointment center of the brain; it is activated by aversive stimuli or in absence of expected rewards (i.e. a condition that should produce “disappointment”). My preliminary results lead me to believe that it plays is central role in sending aversive signals to the DRN that may have a central role in directing proper behavioral responses in aversive contexts or when a punishment is expected. Our objectives in the longer term is to have a better understanding of the central nervous system and its function at the cellular, synaptic and its neural pathways important in the processing of emotional signals crucial to orchestrate our behaviors.

任何生物体最显著的特征之一是它能够对显著的刺激做出适当的行为反应，从而最大限度地提高生存率，并最大限度地减少威胁或不愉快的事件。在哺乳动物中，情绪被认为是一种进化策略，用于检测环境的变化，以指导适当的行为反应。情绪是由大脑边缘系统中相互连接的大脑结构复杂的相互作用产生的。中缝背核（dorsal raphe nucleus，DRN）是大脑的主要神经元能核，它接收来自边缘系统不同核团的信号，并通过在中枢神经系统的不同部位释放神经调节剂5-羟色胺（5-HT）来调节情绪和行为反应。实验结果表明，5-HT在处理令人厌恶的信号方面很重要，而这些信号在预期发生令人厌恶的事情时对协调行为很重要。然而，5-HT控制情绪和行为的机制仍然难以捉摸。这可以通过在体内专门测量和控制多巴胺能通路的技术困难来解释。在这项研究中，我们使用创新的光遗传学和光度学方法，使我们能够解剖参与情绪处理的多巴胺能电路。通过使用几种常用的小鼠行为测试，我们可以将神经活动和行为联系起来。使用创新的光遗传学操作，我们还可以人工激活或抑制特定的神经通路，并观察这些操作如何改变行为反应。具体来说，在这个项目中，我们感兴趣的是了解外侧缰核（LHb）如何控制大脑的主要多巴胺能中心中缝背核（DRN）的活动。LHb被认为是大脑的主要失望中心;它被厌恶的刺激或缺乏预期的奖励（即应该产生“失望”的条件）激活。我的初步研究结果使我相信，它在向DRN发送厌恶信号方面发挥着核心作用，DRN可能在厌恶环境或预期惩罚时指导适当的行为反应方面发挥着核心作用。我们的长期目标是更好地了解中枢神经系统及其在细胞，突触及其神经通路中的功能，这些神经通路在处理对协调我们的行为至关重要的情感信号方面非常重要。