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

阐明基底外侧杏仁核投射到下丘脑外侧在联想学习中的作用

• 批准号: 9192067
• 负责人: Cody Siciliano
• 金额: $ 5.25万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9192067
• 关键词: Amygdaloid structure; Animals; Association Learning; Attention deficit hyperactivity disorder; Automobile Driving; Behavior; Brain region; Calcium; Cells; Conditioned Reflex; Cues; Data; Eating Disorders; Fiber Optics; Functional disorder; Future; Goals; Halorhodopsins; Hypothalamic structure; Image; Imaging Techniques; Imaging technology; Implant; Individual; Investigation; Knowledge; Lateral; Learning; Lesion; Mental Depression; Neurobiology; Neurons; Nose; Opsin; Optics; Organism; Outcome; Pathology; Pathway interactions; Positive Reinforcements; Post-Traumatic Stress Disorders; Probability; Procedures; Process; Psychological reinforcement; Research; Resolution; Rewards; Role; Schizophrenia; Self Administration; Self Stimulation; Signal Pathway; Signal Transduction; Stimulus; Sucrose; Testing; Time; Training; Treatment outcome; Update; Viral; abstracting; addiction; base; calcium indicator; classical conditioning; design; improved; in vivo; in vivo imaging; innovation; neuromechanism; neuropsychiatric disorder; neuropsychiatry; neuroregulation; novel; optogenetics; reinforced behavior; relating to nervous system; research study; response; reward processing; selective expression; technology/technique; treatment strategy

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.

项目总结/摘要 奖励和联想学习过程根据类似的先前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的可能性， 避免负面刺激。联想学习在一系列神经精神疾病中失调 包括抑郁症，饮食失调，精神分裂症和许多其他疾病。因此，了解神经 控制联想学习过程的机制对于设计合理、有效的 药物治疗策略，以改善奖励学习的病理畸变。两个大脑 基底外侧杏仁核（BLA）和外侧下丘脑（LH）这两个区域分别与 编码关于奖励和预测其可用性的刺激的信息。这两个区域 在解剖学上通过从BLA到LH的传入投射连接，然而， 对这一途径的研究，其功能仍然不清楚。我们的初步数据表明， 动物将用鼻子戳刺激BLA至LH通路 奖励/强化。我们推测，内源性激活这一途径可能会灌输奖励 预测刺激与动机价值，从而代表了一个关键的神经基板编码的 联想学习在本申请中提出的具体目标将系统地测试以下假设： BLA到LH的投射是在奖励期间编码预期结果和实际结果之间的关系 学习我们将整合尖端的钙成像技术与途径特异性的病毒表达， 钙指标，以记录在奖励学习的离散方面的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方式阻断该途径的信号传导 以确定该信令对于奖励学习是否是必要的。这些尖端技术的创新整合 实验方法将使我们能够，第一次，确定在这个时间特异性活动， 编码奖励价值的途径。拟议中的实验如果取得成功， 了解联想学习过程，并可能有助于推动新的设计 药物治疗策略。