Role of orbitofrontal signaling of expected outcomes in Pavolvian blocking

巴甫尔阻滞中预期结果的眶额信号的作用

• 批准号: 7328666
• 负责人: Donna Calu Gogerdchi
• 金额: $ 2.97万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-10 至 2010-07-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7328666
• 关键词: Animals; Behavior; Bilateral; Brain; Brain Diseases; Condition; Contralateral; Cues; Data; Drug Addiction; Effectiveness; Expectancy; Face; Fire - disasters; Generations; Human; Learning; Lesion; Measures; Modeling; Neurons; Outcome; Performance; Pharmaceutical Preparations; Phase; Play; Primates; Procedures; Process; Rewards; Role; Signal Transduction; Source; Stimulus; Testing; Time; Training; Ventral Tegmental Area; addiction; base; behavior change; classical conditioning; dopaminergic neuron; expectation; frontal lobe; novel; novel strategies; preference; prevent; relating to nervous system; research study

DESCRIPTION (provided by applicant): A critical component of many human brain diseases may be changes to associative learning functions. For example, much of the aberrant behavior that characterizes drug addiction is driven by environmental cues, which the addict has learned to associate with their drug of choice. Understanding the processes and brain circuits governing such associative learning could generate novel approaches for treating these aspects of addiction. Associative learning is supported by the ability to recognize errors between expected and actual outcomes. Evidence suggests that dopaminergic neurons in ventral tegmental area (VTA) signal these prediction errors through fluctuations in phasic activity. Elevated activity in VTA neurons has been shown to signal unpredicted reward while a decline in activity signals the omission of a predicted reward. However, generating such prediction errors presumably requires comparison of the actual outcome to an a priori expectation for reward. Perhaps the best applicant for generating such outcome expectancies is the orbito frontal cortex (OFC). Not only does OFC send projections to VTA, OFC neurons also fire in anticipation of and during expected outcomes. This activity develops with learning and reflects animals' preferences for different outcomes. This role of expectancy signaling in OFC is also supported by lesion studies, which demonstrate that OFC is critical to behavior guided by outcome expectancies and for new learning in the face of unexpected outcomes. This evidence suggests a model in which OFC signaling provides critical information that leads to the generation or suppression of temporal prediction error signals in VTA to facilitate learning. This proposal will test this hypothesis, using inactivation and single-unit recording to ask how OFC is involved in learning and in the calculation of prediction errors in dopaminergic VTA neurons. For this, we will use a Pavlovian blocking task, in which associative learning for a novel cue is prevented by the simultaneous presentation of a second previously-conditioned cue. Based on our hypothesis, we predict 1) that OFC signaling will correlate with the effectiveness of blocking, 2) that OFC inactivation will impair blocking, 3) that suppression of VTA signaling during blocking (previously observed in primates) will be impaired by OFC inactivation, and 4) that contralateral lesions, which disconnect OFC and VTA, will impair the effectiveness of blocking. The results, whether they confirm or reject our hypothesis, will greatly enhance our understanding of the role OFC and VTA play in simple associative processes that underlie normal and pathological learning.

描述（由申请人提供）：许多人类大脑疾病的一个关键组成部分可能是联想学习功能的改变。例如，吸毒成瘾的许多异常行为都是由环境因素驱动的，吸毒者已经学会将环境因素与他们选择的药物联系起来。了解控制这种联想学习的过程和大脑回路可以产生治疗成瘾这些方面的新方法。联想学习由识别预期结果和实际结果之间的错误的能力提供支持。有证据表明，腹侧被盖区（VTA）的多巴胺能神经元通过阶段性活动的波动来发出这些预测错误的信号。 VTA 神经元的活动升高已被证明预示着不可预测的奖励，而活动的下降则预示着预期奖励的缺失。然而，产生这种预测误差可能需要将实际结果与先验的奖励期望进行比较。也许产生这种预期结果的最佳申请人是眶额皮质（OFC）。 OFC 不仅向 VTA 发送预测，OFC 神经元也会在预期结果和预期结果期间激活。这项活动随着学习而发展，反映了动物对不同结果的偏好。预期信号在 OFC 中的作用也得到了损伤研究的支持，这些研究表明 OFC 对于由结果预期引导的行为以及面对意外结果时的新学习至关重要。这一证据表明了一种模型，其中 OFC 信号提供了关键信息，导致 VTA 中时间预测误差信号的生成或抑制，以促进学习。该提案将测试这一假设，使用失活和单单元记录来询问 OFC 如何参与多巴胺能 VTA 神经元的学习和预测误差的计算。为此，我们将使用巴甫洛夫阻塞任务，其中通过同时呈现第二个先前条件提示来阻止对新提示的联想学习。根据我们的假设，我们预测：1）OFC信号传导将与阻断的有效性相关，2）OFC失活将损害阻断，3）OFC失活将损害阻断期间VTA信号传导的抑制（之前在灵长类动物中观察到），4）断开OFC和VTA的对侧病变将损害阻断的有效性。结果，无论它们证实还是拒绝我们的假设，都将极大地增强我们对 OFC 和 VTA 在正常和病理学习基础的简单联想过程中所发挥的作用的理解。