Elucidating the role of basolateral amygdala projections to the lateral hypothalamus in associative learning

项目摘要/摘要 奖赏和联想学习过程根据类似的研究结果指导未来的行为 设置。这些过程对生存至关重要，因为它们增加了获得奖励和 避免负面刺激。联想学习在一系列神经精神疾病中调节失调 这些疾病包括抑郁症、饮食失调、精神分裂症和许多其他疾病。因此，理解神经 控制联想学习过程的机制对于设计合理、有效的学习过程至关重要 改善奖赏学习中病理异常的药物治疗策略。两个大脑 杏仁基底外侧核(BLA)和下丘脑外侧核(LH)这两个区域分别与 对有关奖励和预测其有效性的刺激的信息进行编码。这两个地区是 然而，在解剖学上，由BLA到LH的传入投射联系在一起，缺乏 对这一途径的研究，其功能仍不清楚。我们的初步数据表明 动物将鼻子戳向刺激BLA到LH的通路，表明这一通路的刺激 是有回报的/强化的。我们假设这一途径的内源性激活可能会灌输奖赏 具有动机价值的预测性刺激，从而代表编码 联想学习。这个应用程序中提出的具体目标将系统地检验以下假设 血乳酸到黄体生成素的投射是对奖励过程中预期结果和实际结果之间的关系进行编码 学习。我们将把尖端的钙成像技术与特定途径的病毒表达结合起来 钙指示剂在奖赏学习的不同方面记录这一途径的内源性活动。 然后，我们将使用光遗传学方法，以时间特异性的方式阻断这一途径的信号。 以确定这种信号是否对奖励学习是必要的。这些尖端技术的创新整合 实验方法将使我们第一次能够确定在时间上的特定活动 编码奖赏价值的路径。拟议实验的成功结果将极大地推动 了解联想学习过程，并可能有助于推动小说的设计 药物治疗策略。

Project Summary/Abstract Reward and associative learning processes guide future behaviors based on previous outcomes in similar settings. These processes are essential to survival as they increase the probability of obtaining rewards and avoiding negative stimuli. Associative learning is dysregulated in a wide array of neuropsychiatric disease states including depression, eating disorders, schizophrenia, and many others. Thus, understanding the neural mechanisms controlling associative learning processes is paramount to designing rationale, efficacious pharmacotherapeutic treatment strategies to ameliorate pathological aberrations in reward learning. Two brain regions, the basolateral amygdala (BLA) and lateral hypothalamus (LH), have both separately implicated in encoding information concerning rewards and the stimuli that predict their availability. These two regions are connected anatomically by an afferent projection from the BLA to LH, however, there is a paucity of investigations into this pathway, and its function remains obscure. Our preliminary data demonstrate that animals will nose poke for stimulation of the BLA to LH pathway indicating that the stimulation of this pathway is rewarding/reinforcing. We hypothesize that endogenous activation of this pathway may imbue reward predicative stimuli with motivational value, and thereby represent a critical neural substrate for encoding of associative learning. The specific aims proposed in this application will systemically test the hypothesis that the BLA to LH projection is encoding the relationship between expected and actual outcomes during reward learning. We will integrate cutting-edge calcium imaging technologies with pathway-specific viral expression of calcium indicators to record the endogenous activity of this pathway during discrete aspects of reward learning. We will then use optogenetic approaches to occlude signaling of this pathway in a temporally specific manner to determine if this signaling is necessary for reward learning. The innovative integration of these cutting-edge experimental approaches will allow us to, for the first time, determine the temporally specific activity in this pathway that encodes reward value. A successful outcome of the proposed experiments will greatly advance out understanding of associative learning processes, and may help to drive the design of novel pharmacotherapeutic treatment strategies.