Patterning valence specific amygdala memory by dorsal tegmental area (DTA) and ventral tegmental area (VTA) dopamine (DA) subsystems

通过背侧被盖区（DTA）和腹侧被盖区（VTA）多巴胺（DA）子系统对价特异性杏仁核记忆进行模式化

• 批准号: 449735246
• 负责人: Professor Dr. Volkmar Leßmann
• 金额: --
• 依托单位: Research Institute of Molecular Pathology (IMP)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/449735246?language=en
• 关键词: Patterning; valence; specific; amygdala; memory

The amygdala is a key structure for the association of Pavlovian conditioned (CS) to unconditioned (US) stimuli. The basolateral complex of the amygdala (BLA) integrates CS information from the auditory cortex and aversive US information from thalamic andsensory cortical inputs. Signals are then relayed via an inhibitory network of primarily central lateral amygdala (CEl) SST+ and PKC delta+ neurons to basal forebrain and the brainstem nuclei, thereby controlling fear behaviors (Tovote, 2016). Dopamine (DA) neurons located in the dorsal tegmental area (DTA neurons), are interconnected with the basolateral (BLA)- central amygdala (CE) circuitry. The CE-projecting DTA neurons send a prediction error coupled DAergic reinforcement signal to the CE. Importantly, this signal rewires the BLA to CEl neuronal connectivity by shifting the weight from PKC delta+ to SST+ synapses. The amygdala has been mostly investigated in aversive fear learning, but there is increasing recognition that the BLA-CE network encodes also reward behaviors. However, the specific BLA-CE circuit rearrangements underlying discriminatory associative reinforcement learning related to negative or positive experiences are not resolved.The ventral tegmental area (VTA) and the mesolimbic reward system also project to the BLA/CE network. Therefore, we propose that BLACE circuitry unifies both negative and positive associative learning by DTA and VTA coupled reinforcement signals, respectively. In support of this view, VTA neuron activity and amygdala DA levels, likely originating from the VTA, increase during reward learning. Likewise, DTA neuron activity and amygdala DA levels, in part originating from DTA cells (unpublished), are strongly increased during exposure to aversive experience. Thus, these two circuits might represent two distinctly different midbrain systems recruited during positively and negatively rated learning paradigms. Moreover, D1 vs. D2 DA receptors are asymmetrically distributed in the genetically defined neuronal subtypes. Here, a simple assumption would imply that DTA and VTA differentially innervate SST+ and PKC delta+ cells. We therefore hypothesize that negatively valenced fear and positively valenced reward signals generate memory traces that differentially map on the genetic BLA to SST+ and BLA to PKC delta+ circuit architecture. We propose that DA originating from the DTA reinforces BLA to SST+ synapses during fear learning, while DA arising from the VTA enhances BLA to CEl PKC delta+ synapses during reward learning. If we will find that aversive and rewarding stimuli affect the network in the same direction, the simple hypothesis would have to be rejected in favor of control of synaptic transmission by DA along the anatomical rostro-caudal gradients rather than along genetically defined neuronal types.

杏仁核是巴甫洛夫条件刺激（CS）与非条件刺激（US）联系的关键结构。杏仁核基底外侧复合体（BLA）整合来自听觉皮层的CS信息和来自丘脑和感觉皮层输入的厌恶性US信息。然后，信号通过主要是中央外侧杏仁核（CEl）SST+和PKC δ +神经元的抑制网络传递到基底前脑和脑干核，从而控制恐惧行为（Tovote，2016）。位于背侧被盖区的多巴胺（DA）神经元（DTA神经元）与基底外侧（BLA）-中央杏仁核（CE）回路相互连接。CE投射DTA神经元向CE发送预测误差耦合的DA能强化信号。重要的是，该信号通过将权重从PKC δ +转移到SST+突触来重新连接BLA到CE 1神经元连接。杏仁核主要是在厌恶恐惧学习中进行研究，但越来越多的人认识到BLA-CE网络也编码奖励行为。然而，与正、负性经验相关的辨别性联想强化学习中的BLA-CE回路的重排并没有得到解决，腹侧被盖区（ventral tegmental area，VTA）和中脑边缘奖赏系统也投射到BLA/CE网络。因此，我们建议，BLACE电路统一消极和积极的联想学习的DTA和VTA耦合强化信号，分别。为了支持这一观点，腹侧被盖区神经元活动和杏仁核DA水平，可能起源于腹侧被盖区，在奖励学习过程中增加。同样地，DTA神经元活动和杏仁核DA水平，部分来源于DTA细胞（未发表），在暴露于厌恶体验期间强烈增加。因此，这两个电路可能代表两个明显不同的中脑系统在积极和消极的评价学习范式。此外，D1与D2 DA受体在遗传上定义的神经元亚型中不对称分布。在这里，一个简单的假设将意味着DTA和VTA差异支配SST+和PKC δ +细胞。因此，我们假设负价的恐惧和正价的奖励信号产生的记忆痕迹，差异映射的遗传BLA SST+和BLA PKC δ +电路架构。我们认为，DA起源于DTA加强BLA SST+突触在恐惧学习，而DA产生的VTA增强BLA CE 1 PKC δ +突触在奖励学习。如果我们发现厌恶性刺激和奖励性刺激以相同的方向影响网络，那么这个简单的假设将不得不被拒绝，而有利于DA沿着解剖学喙尾梯度而不是沿着遗传定义的神经元类型控制突触传递。沿着尾部梯度。