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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709571
• 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官信息，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意义和它们的情绪显著性之间形成适当的联想记忆，以便对传入的感官信息做出适当的反应，并指导未来的行为反应。已知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，而且位于对情绪处理至关重要的大脑区域。在哺乳动物脑中，基底外侧杏仁核（BLA）、腹侧海马（vHIPP）和内侧前额叶皮质（mPFC）形成相互连接的网络，其通过与中脑边缘多巴胺（DA）通路的相互作用来调节情绪学习和记忆形成，所述中脑边缘多巴胺通路包括腹侧被盖区（VTA）和背侧核（NAc）。这些神经区域在功能上相互连接，含有高浓度的大麻素和多巴胺（DA）受体，这两种神经递质系统在情绪处理和学习过程中至关重要。这些神经化学通路参与情绪处理，既包括积极的奖励体验，也包括令人厌恶的事件。使用一系列体内电生理学，神经药理学和行为调查工具，我们的研究计划正在探索这些系统如何在这些过程中功能性地相互作用，以及如何通过DA和大麻素受体系统的信号传导来调节情感感觉处理和联想学习的功能整合。 我们的研究项目的主要目标涉及神经生理学，行为和神经化学表征的神经机制参与处理情绪突出的感觉信息，以及如何通过这些系统的信号可以控制我们如何感知情感价（奖励或厌恶）的感觉经验，以及我们如何形成适当的联想记忆这些情感经验和相关的环境线索。使用在体内的电生理学的联想调节和神经可塑性记录程序，我们正在研究情绪的联想学习和记忆的形成内的单个神经元的啮齿动物的大脑和在行为水平，通过检查关联的神经元的反应，已配对的感觉线索，无论是厌恶（footshock）或奖励（如阿片类药物）的刺激。我们的研究旨在揭示大脑大麻素系统如何通过与大脑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。