Understanding Functional Interactions Between Cannabinoid and Dopamine Signaling Pathways: Impacts on Emotional and Cognitive Processing

研究目的：为了理解世界，大脑必须准确地解释和转换传入的感觉信息的情感和认知意义。大脑如何处理这一连串复杂的感觉信息？在哺乳动物的大脑中，参与这一任务的两个重要神经递质是大麻素和多巴胺(DA)系统。我们的NSERC项目探索了在大麻中发现的特定植物大麻素，Delta-9-四氢大麻酚(THC)和大麻二醇(CBD)如何控制中皮质边缘DA系统，以及这如何调节情绪突显处理、记忆形成和认知。这些大麻素是探索大脑中情绪和认知过程的理想研究工具。它们不仅有力地调节情绪和感官知觉，还与与这些心理现象相关的不同神经药理和相互关联的脑区相互作用；包括前额叶皮质(PFC)、伏隔核(NAC)、腹侧被盖区(VTA)和腹侧海马区(VHIPP)，这些脑区在我们导航世界时对处理情绪、记忆和背景信息至关重要。我们NSERC项目的首要目标是确定大麻如何调节这些脑区的活动，并调节大脑的DA传递系统，这是处理情绪信息、联想学习和认知的基础。科学方法概述：我们的实验室使用了广泛的尖端和集成的行为、分子、电生理和神经成像技术，使我们能够解决从单个神经元水平到行为系统分析水平的研究问题。我们在成像技术方面进行了广泛的创新，最近改进了几项新技术，包括矩阵辅助激光去离子成像技术和RNAScope，使我们能够在高度特定的大脑电路中对特定分子和相关生物标记物进行成像。新颖性和预期意义：我们的研究项目解决了心理学和神经科学接口上最关键的问题之一：大脑如何调节和处理情绪显著的信息？我们正在进行的研究利用行为条件作用范式与体内神经元电生理学和分子成像相结合，在神经化学、神经元和系统分析水平上识别控制情绪处理、学习和记忆的新颖和复杂的神经机制。此外，我们的研究项目正在揭示令人兴奋的新信息，即大麻中发现的特定大麻素如何控制调节情绪记忆形成和认知的特定大脑回路。鉴于加拿大大麻产业的重要性与日俱增，这项正在进行的研究在为大麻相关产品和未来创新制定有效的公共管制战略方面具有重要意义。

RESEARCH OBJECTIVES: To make sense of the world, the brain must accurately interpret and transduce the emotional and cognitive significance of incoming sensory information. How does the brain process this complex barrage of sensory information? In the mammalian brain, two important neurotransmitters involved in this task are the cannabinoid and dopamine (DA) systems. Our NSERC program explores how specific phytocannabinoids found in cannabis, Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), control the mesocorticolimbic DA system and how this regulates emotional salience processing, memory formation and cognition. These cannabinoids represent ideal research tools to explore emotional and cognitive processing in the brain. Not only do they powerfully modulate emotional and sensory perception, they interact with diverse neuropharmacological and interconnected brain regions linked to these psychological phenomena; including, the prefrontal cortex (PFC), nucleus accumbens (NAc), ventral tegmental area (VTA), and ventral hippocampus (vHIPP), brain regions that are critical for processing emotion, memory and contextual information while we navigate the world. The overarching goal of our NSERC program is to determine how cannabinoids modulate the activity of these brain areas and regulate the brain's DA transmission system, which is fundamental for processing emotional information, associative learning and cognition. SUMMARY OF SCIENTIFIC APPROACH: Our lab uses a wide array of cutting-edge and integrative behavioural, molecular, electrophysiological and neural imaging techniques that allow us to address our research questions from the level of the single neuron, to the behavioural systems levels of analysis. We have made extensive innovations in our imaging techniques and have recently refined several new technologies including Matrix-Assisted Laser Deionization Imaging  and RNAScope, allowing us to image specific molecules and relevant biomarkers in highly specific brain circuits. NOVELTY AND EXPECTED SIGNIFICANCE: Our research program addresses one of the most critical questions at the interface of psychology and neuroscience: how does the brain regulate and process emotionally salient information? Using behavioural conditioning paradigms paired with in vivo neuronal electrophysiology and molecular imaging, our ongoing studies are identifying novel and complex neural mechanisms controlling emotional processing, learning and memory, at the neurochemical, neuronal and systems-levels of analysis. In addition, our research program is revealing exciting new information about how specific cannabinoids found in cannabis can control specific brain circuits that regulate emotional memory formation and cognition. This ongoing research is highly relevant given the growing significance of the Canadian Cannabis Industry and in informing the development of effective public regulatory strategies for cannabis-related products and future innovations.