Cholinergic Modulation of Visual Cortical Processing

视觉皮层处理的胆碱能调节

• 批准号: 7662429
• 负责人: Michael Goard
• 金额: $ 1.21万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7662429
• 关键词: Acetylcholine; Adult; Affect; Alzheimer' s Disease; Area; Arousal; Attention; Basal Nucleus of Meynert; Cells; Characteristics; Cholinergic Receptors; Classification; Cognitive; Complex; Electrodes; Memory; Neurons; Pathology; Phase; Process; Property; Rattus; Recurrence; Research; Sensory; Sensory Process; Series; Stimulus; System; Testing; V1 neuron; Visual; Visual Cortex; basal forebrain; cholinergic; cognitive function; insight; public health relevance; receptive field; receptor; relating to nervous system; response; segregation; spatiotemporal; treatment strategy; visual process; visual processing

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.

描述（由申请人提供）：基底前脑（基底核，NB）的胆碱能系统与重要的认知功能有关，例如唤醒、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刺激会导致皮质神经元整体放电率的双向变化。此外，乙酰胆碱 (ACh) 受体不同亚型的层状分布表明，ACh 可以选择性地增强前馈丘脑皮质输入，同时抑制反复发生的皮质内相互作用。因此，尽管皮质胆碱能输入不携带感觉信息，但它可能会调节神经兴奋性和皮质中的有效连接。皮层回路的这些变化可能会通过动态改变皮层感受野 (RF) 特性进而影响视觉处理。我针对 NB 刺激对视觉皮层 RF 的影响提出了一系列假设。在拟议的项目中，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测试这些假设。具体来说，我将描述 NB 刺激对 (i) V1 方向调节、方向选择性和时空感受野 (STRF) 特性 (ii) 视觉反应的空间相位敏感性（简单细胞和复杂细胞之间不同）的影响，以及 (iii) 对自然场景的反应特征的影响。确定 NB 刺激对皮质 RF 的影响将为了解潜在的高级认知过程的持续感觉处理的调节提供重要的见解。公共卫生相关性 基底核是受阿尔茨海默病影响最先也是最严重受损的区域之一。因此，了解它对感觉处理的影响是了解与阿尔茨海默病相关的病理学的重要一步。拟议的研究将阐明参与感觉处理特定变化的受体类型，并提出使用药物的潜在治疗策略。