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: 8204486
• 负责人: Marshall Gilmer Shuler
• 金额: $ 40.59万
• 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/8204486
• 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; relating to nervous system; research study; response; sensory cortex; sensory system; success; theories; visual stimulus

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. 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.

在最近发表的研究结果中，我提供了证据表明将视觉刺激与 随后的奖励导致主要视觉中奖励计时活动的出现 皮质。因此，初级视觉皮层的神经活动不仅仅是重新 视觉提示的呈现，而是与其行为的处理相关 意义。这些发现对于理解我们的大脑如何注入 具有行为意义的感官体验，构成了我长期的基础 职业目标：在一所领先的研究型大学调查之间的相互作用 感觉和奖励系统在适应性行为的形成中。 初级视觉皮层中这种奖励计时活动的特性表明 它是本地生成的。如果是这样，V1 就知道动物获得奖励的情况。 胆碱能系统具有调节 V1 可塑性的理想属性，是最重要的 可能的系统传达这样的奖励信号。因此，拟议的研究是 旨在测试奖励计时活动是在 视觉皮层通过表示奖励的胆碱能输入和丘脑输入的相互作用 表示预测奖励的刺激。 为了解决这个问题，提出的研究计划包括多地点 细胞外记录结合 1) 模仿胆碱能系统的作用 通过光解释放的新颖应用来形成奖励时间 体内乙酰胆碱激动剂，2）局部药理封锁建立的影响 乙酰胆碱对视觉皮层奖励计时形成的影响，以及 3) 劫持 V1 内的胆碱能轴突末端，以证明它们之间的因果关系 活动和学习奖励时间的出现。 模仿、阻断和劫持胆碱能系统的后果 关于 V1 中奖励计时活动的出现将与出现的情况进行比较 在正常大鼠中。如果假设正确，初级视觉皮层可能是一个强大的 用于剖析基于奖励的学习机制的模型系统。获得的洞察力 从这些实验中将了解大脑奖励系统对塑造的作用 感觉系统，我们对此知之甚少，但却直接影响我们的 了解阿尔茨海默病、精神分裂症和药物等人类病理学 虐待。大脑赋予行为意义的机制 环境刺激尚不清楚，但推测神经调节 “奖励”系统将行为结果与之前的神经活动联系起来。 在这里，我测试了这样一个假设：这样一个系统可以调节行为的学习。 通过模仿、阻止和劫持大脑的视觉皮层来理解初级视觉皮层的意义 胆碱能神经调节系统。这项研究的成功将确立 强化学习理论的实验证据，进一步推进我们的研究 了解学习和记忆以及认知的神经机制 由于疾病和衰老而造成的损害。