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在初级视觉皮层 4c 层对丘脑输入增益进行双向、任务依赖性控制。

• 批准号: 10397023
• 负责人: Anita A Disney
• 金额: $ 37.65万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397023
• 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; 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.

项目概要/摘要 控制从眼睛到达初级视觉皮层 (V1) 的输入是改变视觉效果的有力手段。 所有后续视觉信息处理的结果即该视觉输入的强度（或增益）。 皮层可以动态修改并不存在争议，但关于如何动态修改皮层的争论仍在继续 目前，有详细描述的机制来修改增益的强度。 然而，基于其他视觉输入（例如对比度增益控制和归一化）的视觉输入。 行为和认知状态（例如注意力）对皮质处理的修改几乎肯定会出现 来自视觉通路外部的电路，我们对这种视网膜外视觉控制是如何进行的知之甚少 对猕猴的解剖学研究表明，胆碱能和 血清素能系统强烈针对皮层视觉输入部位——丘脑接受层 (4c) 在 V1 中，该定位定位了胆碱能和血清素能系统来控制的程度。 来自眼睛的信息被处理，因此它是否以及如何被感知。 乙酰胆碱和血清素双向控制皮质的“大门”，从而使乙酰胆碱增加（并且 血清素降低）眼睛输入的强度我们将因果地操纵这种调节。 主动视觉期间第 4c 层的控制，并确定对神经反应和 在神经层面，我们将确定第 4c 层引起的增益变化传播的程度。 到其他层，包括传播发生的条件以及传播信号的形式 我们还将确定这些增益效果对行为的影响。 神经调节器允许状态变量（例如唤醒和动机）动态地重新平衡皮质 处理至关重要：十种最常使用的精神科药物中有八种针对神经调节 系统，就像唯一批准的痴呆症药物治疗一样，它是通过控制来实现的。 人们普遍认为神经调节剂可以改变我们（和大脑）的感知、认知和行为。 这些药物通过改变后期皮质处理来发挥作用，但解剖学表明我们同时存在 我们将阐明背后的机制，并确定皮质输入的早期修改。 所有后续处理都依赖于早期控制的后果。