Cholinergic Modulation of Visual Cortical Processing

描述(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，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，刺激NB会引起皮层神经元整体放电频率的双向变化。此外，不同亚型乙酰胆碱(ACh)受体的层流分布表明，ACh可以选择性地促进前馈丘脑皮质的输入，同时抑制皮质内反复发生的相互作用。因此，尽管皮质胆碱能输入不携带感觉信息，但它可能调节皮层的神经兴奋性和有效连接。大脑皮层回路中的这些变化可以通过动态改变大脑皮层感受野(RF)属性进而影响视觉处理。我已经提出了一系列关于刺激NB对视觉皮质RFS的影响的假说。在拟议的项目中，我将通过刺激NB，同时对成年大鼠视皮层神经元进行多电极记录来检验这些假说。具体地说，我将描述刺激NB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(简单和复杂细胞之间的不同)的空间相位敏感性；以及(Iii)对自然场景的反应特征。确定刺激NB对皮层RFs的影响将为正在进行的感觉加工的调制提供重要的见解，这可能是更高水平认知过程的基础。与公共卫生相关的基核是受阿尔茨海默病影响最早也是最严重的地区之一。因此，了解它对感觉处理的影响是理解与阿尔茨海默病相关的病理机制的重要一步。这项拟议的研究将阐明与感觉处理的特定变化有关的受体类型，并建议使用药理学试剂的潜在治疗策略。

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.