Cholinergic Modulation of Visual Cortical Processing

描述（由申请人提供）：基底前脑（基底核，NB）的胆碱能系统涉及重要的认知功能，如唤醒、注意力和记忆，但对该系统如何影响皮质处理知之甚少。先前的研究表明，NB刺激引起皮质神经元的整体放电率的双向变化。此外，不同亚型的乙酰胆碱（ACh）受体的层状分布表明，ACh可以选择性地提高前馈丘脑皮质输入，同时抑制经常性的皮质内的相互作用。因此，虽然皮质胆碱能输入不携带感觉信息，但它可能起调节皮质中神经兴奋性和有效连接的作用。皮质回路中的这些变化可能反过来通过动态改变皮质感受野（RF）特性来影响视觉处理。我已经产生了一系列的假设，NB刺激对视觉皮层RF的影响。在这个项目中，我将通过刺激NB同时对成年大鼠视觉皮层的神经元进行多电极记录来验证这些假设。具体而言，我将表征NB刺激对（i）V1方向调谐，方向选择性和时空感受野（STRF）特性的影响（ii）视觉反应的空间相位敏感性（简单和复杂细胞之间的差异），以及（iii）对自然场景的响应特性。确定NB刺激对皮质RF的影响将为正在进行的感觉处理的调制提供重要的见解，该感觉处理可能是更高层次认知过程的基础。公共卫生相关性基底核是受阿尔茨海默病影响的第一个和最严重的受损区域之一。因此，了解它对感觉处理的影响是了解阿尔茨海默病相关病理学的重要一步。拟议的研究将阐明参与感觉处理特定变化的受体类型，并提出使用药理学药物的潜在治疗策略。

DESCRIPTION (provided by applicant): The cholinergic system of basal forebrain (nucleus basalis, NB) has been implicated in important cognitive functions such as arousal, attention, and memory, yet little is known of how this system affects cortical processing. Previous studies have shown that NB stimulation causes bi-directional changes in the overall firing rate of cortical neurons. Additionally, the laminar distributions of different subtypes of acetylcholine (ACh) receptors suggest that ACh can selectively boost feedforward thalamocortical inputs while suppressing recurrent intracortical interactions. Thus, although cortical cholinergic input does not carry sensory information, it may act to modulate neural excitability and effective connectivity in the cortex. These changes in the cortical circuit may in turn affect visual processing by dynamically altering cortical receptive field (RF) properties. I have generated a series of hypotheses on the effect of NB stimulation on visual cortical RFs. In the proposed project, I will test these hypotheses by stimulating the NB while making multielectrode recordings from neurons in the adult rat visual cortex. Specifically, I will characterize the effects of NB stimulation on (i) V1 orientation tuning, direction selectivity, and spatiotemporal receptive field (STRF) properties (ii) spatial phase sensitivity of visual responses (which differs between simple and complex cells), and (iii) response characteristics to natural scenes. Determining the effects of NB stimulation on cortical RFs will provide important insights into the modulation of ongoing sensory processing that potentially underlies higher-level cognitive processes. PUBLIC HEALTH RELEVANCE Nucleus Basalis is one of the first and most severely damaged areas affected by Alzheimer's disease. Thus, understanding what effect it has on sensory processing represents an important step in understanding the pathologies associated with Alzheimer's disease. The proposed research will elucidate the receptor types involved in specific changes to sensory processing as well as suggest potential treatment strategies using pharmacological agents.