The neuronal mechanism of reward timing in the primary visual cortex

在最近发表的研究结果中，我提供了证据， 随后的奖励导致初级视觉中奖励-计时活动的出现 皮层因此，初级视觉皮层的神经活动不仅仅是一个简单的重新- 视觉提示的呈现，而是将其行为的处理 意义这些发现对于理解我们的大脑如何向 感官体验与行为意义，并形成了我长期的基础， 职业目标：在一所领先的研究型大学，研究 感官和奖励系统在适应行为的形成。 初级视觉皮层中这种奖励计时活动的特性表明， 它是在本地产生的。如果是这样的话，V1参与了动物获得奖励的过程。 由于V1具有理想的介导可塑性的属性，胆碱能系统是最重要的 可能的系统来传达这样的奖励信号。因此，拟议的研究是 针对测试的假设，奖励时间的活动是产生在 通过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，提出的研究方案包括多个地点 细胞外记录结合1）模拟胆碱能系统的作用 在奖励时机的形成中， 乙酰胆碱激动剂在体内，2）局部药理学封锁，以建立影响 乙酰胆碱对视觉皮层奖励时间形成的影响，以及3）劫持 V1内的胆碱能轴突终末，以证明它们之间的因果关系。 活动和习得性奖励时机的出现。 模仿、阻断和劫持胆碱能系统的后果 在V1中出现的奖励时间活动将与出现的奖励时间活动进行比较。 在正常的老鼠。如果这个假设是正确的，初级视觉皮层可能是一个强大的 剖析奖励式学习机制的模型系统。获得的洞察力 从这些实验将告知大脑奖励系统的作用， 感官系统，其中知之甚少，但直接影响我们的 了解人类的病理，如阿尔茨海默氏症，精神分裂症，和药物 虐待大脑将行为意义归因于 环境刺激是未知的，尽管假设神经调节 “奖赏”系统将行为的结果与先前的神经活动联系起来。 在这里，我测试的假设，一个这样的系统介导的学习行为 这意味着在初级视觉皮层通过模仿，阻塞，劫持大脑的 胆碱能神经调节系统这项研究的成功将建立 强化学习理论的实验证据，进一步推动了我们的 了解学习和记忆的神经机制以及认知的神经机制。 由于疾病和衰老而造成的损伤。

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.