Dopamine and Cannabinoid Modulation of Emotional Memory in the Mesocorticolimbic System

多巴胺和大麻素对中皮质边缘系统情绪记忆的调节

• 批准号: RGPIN-2016-05048
• 负责人: Laviolette, Steven
• 金额: $ 2.99万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688231
• 关键词: Dopamine; Cannabinoid; Modulation; Emotional; Memory

To make sense of the world around us, the brain must constantly filter incoming sensory information and accurately interpret the emotional significance and relevance of these inputs. Of equal importance, the brain must form appropriate associative memories between the meaning of specific environmental cues and their emotional salience in order to respond appropriately to incoming sensory information and guide future behavioural responses. Two neurochemical substrates that are known to regulate affective states and associative memory formation are the brain's dopamine (DA) and cannabinoid receptor systems. These systems not only functionally interact with one another, but are localized in brain regions that are critical for emotional processing. In the mammalian brain, the basolateral amygdala (BLA), ventral hippocampus (vHIPP) and medial prefrontal cortex (mPFC) form an interconnected network that regulates emotional learning and memory formation through interactions with the mesolimbic dopamine (DA) pathway, comprising the ventral tegmental area (VTA) and nucleus accumbens (NAc). These neural regions are functionally interconnected and contain high concentrations of cannabinoid and dopamine (DA) receptors, two neurotransmitter systems that are critical in the processing of emotional processing and learning. The involvement of these neurochemical pathways in emotional processing extends to both positive rewarding experiences as well as aversive events. Using a series of in vivo electrophysiological, neuropharmacological and behavioral investigative tools, our research program is exploring how these systems functionally interact in these processes and how signaling through DA and cannabinoid receptor systems may modulate the functional integration of emotional sensory processing and associative learning.***The primary goal of our research project involves the neurophysiological, behavioural and neurochemical characterization of neural mechanisms involved in the processing of emotionally salient sensory information and how signaling through these systems may control how we perceive the emotional valence (rewarding or aversive) of sensory experiences and how we form appropriate associative memories between these affective experiences and related environmental cues. Using in vivo electrophysiological associative conditioning and neural plasticity recording procedures, we are examining emotional associative learning and memory formation within single neurons of the rodent brain and at the behavioural levels, by examining associative neuronal responses to sensory cues that have been paired with either aversive (footshock) or rewarding (e.g. opiates) stimuli. Our studies aim to reveal critical new insights into how the brains cannabinoid system may control emotional processing through functional interactions with the brain's dopamine system.***********

为了理解我们周围的世界，大脑必须不断过滤传入的感觉信息，并准确地解释这些输入的情感意义和相关性。同样重要的是，大脑必须在特定环境线索的含义及其情绪突显之间形成适当的联想记忆，以便对传入的感觉信息做出适当反应，并指导未来的行为反应。已知的调节情感状态和联想记忆形成的两种神经化学底物是大脑的多巴胺(DA)和大麻素受体系统。这些系统不仅在功能上相互作用，而且位于大脑中对情绪处理至关重要的区域。在哺乳动物的大脑中，杏仁基底外侧核(BLA)、腹侧海马(VHIPP)和内侧前额叶皮质(MPFC)形成了一个相互联系的网络，通过与包括腹侧被盖区(VTA)和伏隔核(NAC)在内的中脑边缘多巴胺(DA)通路相互作用，调节情绪学习和记忆的形成。这些神经区在功能上是相互联系的，含有高浓度的大麻素和多巴胺(DA)受体，这两个神经递质系统在情绪处理和学习过程中至关重要。这些神经化学通路在情绪处理中的作用延伸到了积极的奖励体验和厌恶的事件。利用一系列体内电生理学、神经药理学和行为学研究工具，我们的研究项目正在探索这些系统如何在这些过程中功能性地相互作用，以及通过DA和大麻素受体系统的信号如何调节情绪感觉处理和联想学习的功能整合。*我们研究项目的主要目标涉及处理情绪显著感觉信息所涉及的神经机制的神经生理、行为和神经化学特征，以及通过这些系统发出的信号如何控制我们如何感知感觉体验的情绪价位(奖赏或厌恶)，以及我们如何在这些情感体验和相关环境线索之间形成适当的联想记忆。使用体内电生理联想条件反射和神经可塑性记录程序，我们正在检测啮齿动物大脑中单个神经元内情绪联想学习和记忆的形成，并在行为水平上，通过检测与厌恶(足部电击)或奖励(例如鸦片类)刺激配对的感觉线索的关联神经元反应。我们的研究旨在揭示大脑大麻素系统如何通过与大脑的多巴胺系统的功能相互作用来控制情绪处理的关键新见解。