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译传入的感官信息的情感和认知意义。大脑是如何处理这些复杂的感官信息的？在哺乳动物的大脑中，参与这项任务的两种重要神经递质是大麻素和多巴胺（DA）系统。我们的NSERC计划探索大麻中发现的特定植物大麻素，δ -9-四氢大麻酚（THC）和大麻二酚（CBD）如何控制中脑皮质边缘DA系统，以及这如何调节情绪显著性处理，记忆形成和认知。这些大麻素是探索大脑中情感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各种神经药理和相互关联的大脑区域相互作用；包括前额叶皮层（PFC）、伏隔核（NAc）、腹侧被盖区（VTA）和腹侧海马体（vHIPP），这些大脑区域在我们导航世界时对处理情感、记忆和上下文信息至关重要。我们NSERC项目的首要目标是确定大麻素如何调节这些大脑区域的活动，并调节大脑的DA传输系统，这是处理情绪信息，联想学习和认知的基础。科学方法总结：我们的实验室使用广泛的前沿和综合行为，分子，电生理和神经成像技术，使我们能够解决我们的研究问题，从单个神经元的水平，到行为系统的分析水平。我们在成像技术方面进行了广泛的创新，最近改进了几种新技术，包括基质辅助激光去离子成像和RNAScope，使我们能够在高度特异性的脑回路中对特定分子和相关生物标志物进行成像。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交叉领域最关键的问题之一：大脑是如何调节和处理情感显著信息的？利用行为调节范式与体内神经元电生理学和分子成像相结合，我们正在进行的研究正在神经化学，神经元和系统水平的分析中确定控制情绪处理，学习和记忆的新颖和复杂的神经机制。此外，我们的研究项目揭示了令人兴奋的新信息，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日益增长的重要性，以及为大麻相关产品和未来创新制定有效的公共监管战略提供信息，这项正在进行的研究具有高度相关性。

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.