The neuronal mechanism of reward timing in the primary visual cortex

初级视觉皮层奖励计时的神经机制

• 批准号: 7563443
• 负责人: Marshall Gilmer Shuler
• 金额: $ 37.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-23 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7563443
• 关键词: Acetylcholine; Adaptive Behaviors; Address; Aging; Agonist; Alzheimer' s Disease; Animals; Association Learning; Behavior; Behavioral; Biological Models; Brain; Cell Nucleus; Cholinergic Agonists; Cues; Disease; Drug abuse; Etiology; Goals; Human Pathology; Impaired cognition; Impairment; Infection; Learning; Mediating; Memory; Neurons; Outcome; Photic Stimulation; Process; Property; Psychological reinforcement; Publishing; Rattus; Research; Rewards; Role; Schizophrenia; Sensory; Shapes; Signal Transduction; Site; Stimulus; Synapses; System; Testing; Thalamic structure; Time; Universities; Visual; Visual Cortex; Water; area striata; awake; base; career; cholinergic; experience; extracellular; in vivo; insight; neuromechanism; neurotensin mimic 1; novel; photoactivation; programs; public health relevance; relating to nervous system; research study; response; sensory cortex; sensory system; success; theories; visual stimulus

Description (provided by applicant): In recently published findings, I provided evidence that pairing visual stimuli with subsequent reward leads to the emergence of reward-timing activity in the primary visual cortex. Therefore, neural activity in the primary visual cortex is not simply a re- presentation of a visual cue, but rather relates the processing of its behavioral significance. These findings have implications for understanding how our brains imbue sensory experience with behavioral meaning, and forms the basis of my long-term career goal: to investigate, at a leading research university, the interaction between sensory and reward systems in the formation of adaptive behaviors. The properties of this reward timing activity in the primary visual cortex suggest that it is generated locally. If so, V1 is privy to the acquisition of reward by the animal. With attributes ideal for mediating plasticity in V1, the cholinergic system is the most likely system to convey such a reward signal. Therefore, the proposed research is directed towards testing the hypothesis that reward timing activity is generated within the visual cortex by the interaction of cholinergic inputs signifying reward and thalamic inputs signifying the stimuli that predict reward. To address this question, the research program proposed consists of multi-site extracellular recordings combined with 1) mimicking the action of the cholinergic system in the formation of reward timing by a novel application of photolytically uncaged acetylcholine agonist in vivo, 2) local pharmacological blockade to establish the impact of acetylcholine on the formation of reward timing in the visual cortex, and 3) hijacking the cholinergic axonal terminals within V1, to demonstrate causality between their activity and the emergence of learned reward timing. The consequences of mimicking, blocking, and hijacking the cholinergic system on the emergence of reward timing activity in V1 will be compared to that which emerges in normal rats. If the hypothesis is correct, the primary visual cortex could be a powerful model system for dissecting mechanisms of reward-based learning. The insight gained from these experiments will inform upon the role brain reward systems have on shaping sensory systems, of which very little is known, yet which impact directly our understanding of human pathologies such as Alzheimer's, schizophrenia, and drug abuse. PUBLIC HEALTH RELEVANCE The mechanism by which the brain comes to attribute behavioral meaning to environmental stimuli is unknown, though it is hypothesized that neuromodulatory "reward" systems relate the outcome of behavior with preceding neural activity. Here, I test the hypothesis that one such system mediates the learning of behavioral meaning in the primary visual cortex by mimicking, blocking, and hijacking the brain's cholinergic neuromodulatory system. Success in this study would establish experimental evidence for theories of reinforcement learning, furthering our understanding of neural mechanisms of learning and memory and of cognitive impairment due to disease and aging.

描述（由申请人提供）：在最近发表的发现中，我提供了证据，表明将视觉刺激与随后的奖励配对导致奖励观点活动在主要视觉皮层中的出现。因此，主要视觉皮层中的神经活动不仅是视觉提示的重新介绍，而且还与其行为意义的处理有关。这些发现对理解我们的大脑如何将感官体验与行为意义融为一体，并构成了我长期职业目标的基础：在一所领先的研究大学中调查感官和奖励体系之间的相互作用，形成适应性行为。此奖励计时活动在主要视觉皮层中的特性表明它是在本地生成的。如果是这样，V1不愿意从动物那里获得奖励。由于属性是介导V1中可塑性的理想选择，胆碱能系统是传达这种奖励信号的最可能系统。因此，提出的研究是针对检验的假设，即通过胆碱能输入的相互作用在视觉皮层中产生奖励时序活动，这些胆碱能输入表示奖励和丘脑输入，这意味着预测奖励的刺激。为了解决这个问题，提出的研究计划包括多站点外记录与1）结合1）模仿胆碱能系统在形成奖励时机中的作用，这是通过在体内发光的乙酰胆碱激动剂的新型应用，2）本地药理障碍物建立了乙酰胆碱的影响，并建立了乙基甲基甲基乙基的影响，并在乙基甲基链中的影响，形式上了奖励的奖励，并在形式上构成了奖励的奖励，并在形式上构成了奖励的形式，并在形式上构成了形式化的形式化的形式，并在形成了奖励的形式，并在形式上建立了奖励的形式，并在形式上构成了奖励的形式，并在形式上建立了奖励的造型。 V1内的胆碱能轴突终端，以证明其活动与学习奖励时机的出现之间的因果关系。模仿，阻塞和劫持胆碱能系统对V1中奖励定时活动的出现的后果与正常大鼠中出现的后果将进行比较。如果假设正确，则主要视觉皮层可能是剖析基于奖励学习机制的强大模型系统。从这些实验中获得的洞察力将告知脑奖励系统在塑造感觉系统中的作用，而这些角色却几乎不知道，但这直接影响了我们对人类病理的理解，例如阿尔茨海默氏症，精神分裂症和药物滥用。公共卫生相关性大脑赋予环境刺激的行为含​​义的机制尚不清楚，尽管假设神经调节性的“奖励”系统将行为的结果与先前的神经活动联系起来。在这里，我检验了这样一个假设，即这样一个系统通过模仿，阻断和劫持大脑的胆碱能神经调节系统，从而介导了主要视觉皮层中的行为含义的学习。这项研究的成功将为强化学习理论建立实验证据，从而进一步了解我们对学习和记忆的神经机制以及由于疾病和衰老而引起的认知障碍。