Bi-directional, task-dependent control of thalamic input gain, in layer 4c of the primary visual cortex, by the cholinergic and serotonergic neuromodulatory systems

胆碱能和血清素能神经调节系统对初级视觉皮层第 4c 层丘脑输入增益进行双向、任务依赖性控制

• 批准号: 10161528
• 负责人: Anita A Disney
• 金额: $ 6.56万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10161528
• 关键词: Acetylcholine; Affect; Agonist; Anatomy; Anesthesia procedures; Area; Arousal; Attention; Behavior; Behavior Control; Behavioral; Biological Assay; Brain; Calcium Channel; Cognition; Cognitive; Data; Data Analyses; Dementia; Dependence; Detection; Dissection; Dose; Drug Delivery Systems; Drug Targeting; Electrodes; Electrophysiology (science); Eye; Ligands; Location; Macaca; Measures; Mediating; Microdialysis; Modeling; Modification; Monkeys; Motivation; Neuromodulator; Neurons; Nicotine; Nicotinic Receptors; Ocular Dominance; Outcome; Output; Perception; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Positioning Attribute; Prefrontal Cortex; Primates; Process; Property; Psychiatrist; Receptor Activation; Reporting; Resolution; Retina; Rodent; Serotonergic System; Serotonin; Serotonin Receptor 5-HT1B; Signal Transduction; Site; Source; Stimulus; Structure; Synapses; System; Task Performances; Testing; Thalamic structure; Vision; Visual; Visual Cortex; Visual Pathways; Work; active vision; alertness; area V1; area striata; base; cholinergic; density; design; experimental study; extrastriate visual cortex; gain of function; indexing; innovation; monocular; neuroregulation; novel; parent grant; receptive field; receptor; receptor expression; relating to nervous system; response; species difference; targeted treatment; treatment strategy; virtual; visual control; visual information; visual processing; voltage

PROJECT SUMMARY / ABSTRACT Controlling the input that arrives at the primary visual cortex (V1) from the eyes is a powerful means for altering the outcome of all subsequent processing of visual information. That the strength (or gain) of this visual input to cortex can be dynamically modified is not controversial, but debate continues regarding the means by which that gain control is achieved. Currently, there are well-described mechanisms for modifying the strength of visual input based on other visual input (such as contrast gain control and normalization). However, modification of cortical processing by behavioral and cognitive states (such as attention) almost certainly arises from circuits outside the visual pathway, and we know far less about how this extra-retinal control of vision is achieved. Anatomical studies in macaque monkeys indicate that modulation by the cholinergic and serotonergic systems is strongly directed toward the site of visual input to cortex – the thalamic-recipient layer (4c) in V1. This localization positions the cholinergic and serotonergic systems to control the extent to which information from the eyes gets processed, and therefore whether and how it is perceived. We hypothesize that acetylcholine and serotonin bi-directionally control the “gate” to cortex, such that acetylcholine increases (and serotonin decreases) the strength of the input from the eyes. We will causally manipulate this modulatory control of layer 4c during active vision, and determine the resulting effects on both neural responses and behavior. At the neural level, we will determine the extent to which gain changes induced in layer 4c propagate to other layers, including the conditions under which propagation occurs, and the form the propagated signal takes. We will also determine the impact of these gain effects on behavior. Understanding how neuromodulators allow state variables (such as arousal and motivation) to dynamically rebalance cortical processing is critically important: Eight of the ten most-prescribed psychiatric drugs target neuromodulatory systems, as does the only approved drug treatment for dementia. Thus, it is through controlling neuromodulators that we (and the brain) modify perception, cognition, and behavior. It is generally assumed that these drugs act by altering late-stage cortical processing, but the anatomy points us towards a concurrent early modification of cortical input. We will elucidate the mechanism(s) behind, and determine the consequences of, that early control upon which all later processing depends.

项目摘要 /摘要 控制从眼睛到达主要视觉皮层（V1）的输入是改变的强大手段 随后的所有视觉信息处理的结果。此视觉输入的强度（或增益） 皮质可以动态修改不是引起争议的，但是关于以下方式的争论仍在继续 获得了收益的控制。当前，有很好的描述机制来修改 基于其他视觉输入的视觉输入（例如对比增益控制和归一化）。然而， 通过行为和认知状态（例如注意）对皮质处理的修改几乎可以肯定会产生 从视觉途径外面的圈子中，我们对视视外视力控制的了解远不止于此 成就了。猕猴的解剖学研究表明，胆碱能和 血清素能系统强烈地针对视觉输入到皮质的位置 - 丘脑 - 恢复层 （4C）在V1中。这种定位定位胆碱能和血清素能系统，以控制 来自眼睛的信息被处理，因此是否以及如何看待它。我们假设这一点 乙酰胆碱和5-羟色胺双向控制皮质的“栅极”，使乙酰胆碱增加（和 5-羟色胺下降）眼睛输入的强度。我们将因果操作这种调节 在主动视力中控制第4C层，并确定对神经反应的影响和 行为。在神经层面，我们将确定第4C层中引起的增益变化的繁殖程度 到其他层，包括发生传播的条件以及传播信号的形式 带。我们还将确定这些增益对行为的影响。了解如何 神经调节剂允许状态变量（例如唤醒和动机）动态重新平衡皮质 加工至关重要：十种最常规的精神药物中的八个靶向神经调节性 系统，唯一批准的痴呆药物治疗也是如此。那是通过控制 我们（和大脑）修改感知，认知和行为的神经调节剂。通常假定 这些药物通过改变后期皮质加工来起作用，但解剖学将我们指向并发 皮质输入的早期修饰。我们将阐明背后的机制，并确定 后来的所有后期处理都取决于这种早期控制的后果。