Lateral habenula circuits for the regulation of goal-directed behavior

用于调节目标导向行为的外侧缰核回路

• 批准号: 10657639
• 负责人: Melissa Rhoads Warden
• 金额: $ 37.67万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657639
• 关键词: Affect; Animals; Attention deficit hyperactivity disorder; Basal Ganglia; Behavior; Behavioral; Bipolar Disorder; Brain Stem; Cell Nucleus; Consumption; Data; Disease; Dopamine; Environment; Equilibrium; Event; Failure; Fiber; Fire - disasters; Functional disorder; Globus Pallidus; Glutamates; Goals; Habenula; Human; Hypothalamic structure; Investigation; Lateral; Medial; Mental Depression; Methods; Midbrain structure; Monitor; Mus; Negative Valence; Neurons; Obsessive-Compulsive Disorder; Optical Methods; Optics; Photometry; Physiological; Positive Valence; Preoptic Areas; Process; Prosencephalon; Punishment; Reaction; Regulation; Resolution; Rewards; Role; Science; Serotonin; Testing; Therapeutic Intervention; Time; Water; Work; addiction; dorsal raphe nucleus; driving force; endopeduncular nucleus; insight; microendoscopy; neural; neural circuit; neurophysiology; neuroregulation; optogenetics; response

Project Summary How do we decide whether to continue pursuing a goal or abandon the quest? Survival requires both the ability to persist in behavior directed toward a goal and the ability to determine when it is time to stop, a finely-tuned balance of perseverance and disengagement. The optimal balance between goal-directed and disengaged behavior differs depending on internal state and the environment, and sensitive, context-appropriate regulation of this balance is both essential and challenging. Excessive or insufficient goal-directed behavior is associated with psychiatric dysfunction ranging from attention deficit hyperactivity disorder to obsessive compulsive disorder to addiction. Disengagement from goal pursuit is an essential process, and it can be elicited by factors with either negative or positive valence. For example, an animal might stop attempting to obtain water because its actions to obtain water have failed, because it has already consumed enough water, or because it needs to quickly respond to an imminent threat to survival. Are the circuits that suppress goal-directed behavior in response to action failure the same as those that suppress goal-directed behavior after satisfying homeostatic needs or in response to threats? The LHb is a major conduit of information from the forebrain to brainstem neuromodulatory centers, and LHb neural activity suppresses midbrain dopamine neural activity via the GABAergic rostromedial tegmental nucleus (RMTg). LHb neurons fire when animals don’t receive expected rewards and when they receive punishments, and stimulation of LHb neurons and glutamatergic inputs to the LHb promotes behavioral avoidance. The objective of this study is to systematically probe the functional role of lateral habenula (LHb) circuits in regulating disengagement from goals in response to action failure, homeostatic resolution, and threat. We will use optical methods to monitor and control LHb neural circuits in order to characterize the long-timescale dynamics and functional role of LHb neurons in regulating the balance between goal-directed and disengaged behavioral states.

项目摘要 我们如何决定是继续追求目标还是放弃追求？生存需要同时具备 坚持朝着一个目标的行为，并有能力决定什么时候停止，一个微调， 毅力和解脱的平衡。目标导向和脱离之间的最佳平衡 行为的不同取决于内部状态和环境，以及敏感的、与环境相适应的调节 这种平衡既重要又具有挑战性。过度或不足的目标导向行为与 从注意力缺陷多动障碍到强迫症 从紊乱到成瘾从目标追求中脱离出来是一个必要的过程，它可以由各种因素引起 带负价或正价的。例如，动物可能会停止试图获得水， 它获取水的行动失败了，因为它已经消耗了足够的水，或者因为它需要 迅速应对迫在眉睫的生存威胁是抑制目标导向行为的回路， 对行动失败的反应与满足自我平衡后抑制目标导向行为的反应相同 是为了应对威胁，还是为了应对威胁？LHb是从前脑到脑干的主要信息通道 LHb神经活动通过神经调节中心抑制中脑多巴胺神经活动。 GABA能头内侧被盖核（RMTg）。当动物没有收到预期的LHb神经元时， 奖励和当他们接受惩罚，并刺激LHb神经元和神经元的输入， LHb促进行为回避。本研究的目的是系统地探讨 外侧缰核（LHb）回路在动作失败时调节脱离目标， 自我平衡解决和威胁我们将使用光学方法来监测和控制LHb神经回路， 为了表征LHb神经元在调节平衡中的长时间尺度动力学和功能作用， 在目标导向和脱离行为状态之间。

项目成果

Tonic activity in lateral habenula neurons acts as a neutral valence brake on reward-seeking behavior.

侧向Habenula神经元中的滋补活性是对寻求奖励行为的中性价制动器。

• DOI: 10.1016/j.cub.2022.08.016
• 发表时间: 2022-10-24
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Post, Ryan J.;Bulkin, David A.;Ebitz, R. Becket;Lee, Vladlena;Han, Kasey;Warden, Melissa R.
• 通讯作者: Warden, Melissa R.