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

项目摘要/摘要 控制从眼睛到达初级视觉皮质(V1)的输入是一种强有力的改变手段 对视觉信息进行所有后续处理的结果。这一视觉输入的强度(或增益) 皮质可以动态修改并不存在争议，但关于通过什么方式进行修改的争论仍在继续 实现了这种增益控制。目前，有一些描述良好的机制可用于修改 基于其他视觉输入的视觉输入(如对比度增益控制和归一化)。然而， 几乎可以肯定的是，行为和认知状态(如注意力)对大脑皮层的加工进行了调整 从视觉通路之外的回路，我们对视网膜外控制视觉的方式知之甚少 已实现。猕猴的解剖学研究表明，胆碱能和 5-羟色胺能系统强烈地指向皮层的视觉输入部位--丘脑接受层 (4C)在V1。这种定位定位了胆碱能和5-羟色胺能系统，以控制 来自眼睛的信息被处理，因此是否被感知以及如何被感知。我们假设 乙酰胆碱和5-羟色胺双向控制着通往大脑皮层的“大门”，从而使乙酰胆碱增加(和 5-羟色胺减少)来自眼睛的输入的强度。我们会随心所欲地操纵这个调节器 在主动视觉期间对4c层的控制，并确定由此对神经反应和 行为。在神经层面，我们将确定在4c层引起的增益变化传播的程度。 到其他层，包括发生传播的条件和传播信号的形式 索要。我们还将确定这些增益效应对行为的影响。了解如何 神经调节剂允许状态变量(如觉醒和动机)动态地重新平衡大脑皮层 加工过程至关重要：十种最常用的精神药物中有八种是针对神经调节的 系统，以及唯一被批准的治疗痴呆症的药物。因此，它是通过控制 我们(和大脑)调节感知、认知和行为的神经调节剂。人们通常认为 这些药物通过改变晚期皮质加工而起作用，但解剖学表明我们倾向于同时 皮质输入的早期修改。我们将阐明(S)背后的机制，并确定 所有后续处理所依赖的早期控制的后果。

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.