Dopamine and cannabinoid modulation of emotional memory in the amygdala-prefrontal cortical circuit

为了理解我们周围的世界，大脑必须不断地过滤一连串传入的感觉信息，并准确地解释这些输入的情感意义和相关性。在哺乳动物的大脑中，杏仁基底外侧核(BLA)、腹侧被盖区(VTA)和内侧前额叶皮质(MPFC)对情绪突显感觉信息的处理和整合以及学习和记忆的形成至关重要。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。我们研究项目的主要目标涉及神经生理、行为和神经化学特征，这些神经机制涉及情绪上突出的感觉信息的处理。使用体内电生理联想条件反射和神经可塑性记录程序，我们通过检测神经元对气味线索的反应来检验啮齿动物BLA和mPFC单个神经元的情绪联想学习，这些气味线索已经与情绪显著体验(足部电击)关联地配对。我们的研究项目将通过研究特定的DA受体亚型和大麻素信号系统在情绪记忆编码、回忆和消退的不同阶段所起的作用来探索这种神经回路。使用行为药理学和体内多单位清醒行为啮齿动物的综合记录，我们将研究来自VTA和BLA的输入如何在功能上相互作用，以调节mPFC、BLA和VTA电路中单个神经元和神经元集合的情绪联想学习和记忆编码的处理。了解这种神经回路如何参与编码情绪显著的习得联系，将为单个神经元和分布式神经网络如何编码和表达情绪记忆提供基本的见解，并识别控制大脑如何将情绪显著分配给传入感觉信号的特定神经机制。

To make sense of the world around us, the brain must constantly filter a barrage of incoming sensory information and accurately interpret the emotional significance and relevance of these inputs. In the mammalian brain, the basolateral amygdala (BLA), ventral tegmental area (VTA) and medial prefrontal cortex (mPFC) are critical for the processing and integration of emotionally salient sensory information, learning and memory formation. 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 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. Using in vivo electrophysiological associative conditioning and neural plasticity recording procedures, we examine emotional associative learning within single neurons of the rodent BLA and mPFC by examining neuronal responses to odour cues that have been associatively paired with emotionally salient experiences (footshock). Our research program will explore this neural circuitry by examining the roles of specific DA receptor subtypes and cannabinoid signaling systems during distinct phases of emotional memory encoding, recall and extinction. Using an integrative combination of behavioural pharmacology and in vivo, multi-unit recordings in awake, behaving rodents, we will examine how inputs from the VTA and BLA functionally interact to mediate the processing of emotional associative learning and memory encoding in single neurons and neuronal ensembles within the mPFC, BLA and VTA circuitry. Understanding how this neural circuitry may be involved in the encoding of emotionally salient learned associations will provide fundamental insights into how both single neurons and distributed neural networks may encode and express emotional memory and identify the specific neural mechanisms that control how the brain assigns emotional salience to incoming sensory signals.