CRCNS: Cholinergic regulation of sensory computation

CRCNS：感觉计算的胆碱能调节

• 批准号: 7615854
• 负责人: Thomas A Cleland
• 金额: $ 41.07万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615854
• 关键词: Acetylcholine; Address; Afferent Neurons; Area; Attention; Behavioral; Behavioral Model; Brain; Cells; Cholinergic Agents; Cholinergic Receptors; Chromosome Pairing; Collaborations; Computer Simulation; Data; Development; Electrophysiology (science); Esthesia; In Vitro; Individual; Investigation; Knowledge; Mediating; Modeling; Muscarinic Acetylcholine Receptor; Muscarinics; Neurons; Nicotinic Receptors; Noise; Odors; Perception; Physiology; Process; Property; Rattus; Receptor Activation; Regulation; Relative (related person); Research; Rest; Role; Scientist; Sensory; Sensory Process; Signal Transduction; Slice; Stimulus; Synapses; Synaptic Transmission; System; Testing; base; behavioral pharmacology; cholinergic; computer studies; experimental analysis; improved; in vivo; interdisciplinary approach; neural circuit; olfactory bulb; olfactory stimulus; programs; receptive field; relating to nervous system; research study; response; simulation

DESCRIPTION (provided by applicant): This proposal presents a multidisciplinary approach to understanding a fundamental property of sensory processing: the modulation of sensory perception by acetylcholine. The proposal addresses this question in the olfactory bulb of rats, using a combination of computational modeling, brain slice physiology, in vivo electrophysiology and behavioral pharmacology. The mammalian olfactory system offers several unique advantages for such studies. First, the olfactory system is anatomically relatively simple and this simplicity has resulted in an extensive knowledge of its synaptic connections and physiology. Second, because olfactory bulb principal neurons are a single synapse removed from sensory neurons, a relatively clear relationship between neural representations in the bulb and the perceptual properties of olfactory signals has been established. Third, this knowledge in turn has enabled the development of computational models crucial for the interpretation and integration of experimental data. A collaborative effort between three labs will investigate the interplay between muscarinic and nicotinic receptor activation and the functional consequences of their coordinated activation. Specifically, we will (1) determine the effects of muscarinic and nicotinic receptor activation on olfactory bulb neural circuits in a detailed biophysical model, (2) test the cellular and synaptic effects of such modulation using brain slice electrophysiology, (3) use in vivo electrophysiology to determine the effect of cholinergic modulation on odor responses, and (4) test the functional predictions arising from these experiments in behavioral pharmacology experiments. Taken together, the proposed simulations and experiments will elucidate how nicotinic and muscarinic receptors interact within a coordinated neural circuit to improve contrast and signal-to-noise properties in early olfactory processing.

描述（由申请人提供）：该提案提出了一种多学科的方法来理解感官处理的基本特性：乙酰胆碱对感觉感知的调节。该提案使用计算建模，脑切片生理，体内电生理学和行为药理学的组合在嗅球的大鼠嗅球中解决了这个问题。哺乳动物嗅觉系统为此类研究提供了几个独特的优势。首先，嗅觉系统在解剖学上是相对简单的，这种简单性使人们对其突触连接和生理学有了广泛的了解。其次，由于嗅球主神经元是从感觉神经元中取出的单个突触，因此已经建立了灯泡中神经表示与嗅觉信号的感知特性之间的相对清晰的关系。第三，这些知识又使计算模型的开发对于解释和集成实验数据至关重要。三个实验室之间的协作工作将研究毒蕈碱和烟碱受体激活之间的相互作用以及其协调激活的功能后果。具体而言，我们将（1）确定在详细的生物物理模型中毒蕈碱和烟碱受体激活对嗅觉泡沫神经回路的影响，（2）测试使用脑部SLICE电生理学调节的细胞和突触效应，（3）在Vivo中使用（3）电生理学确定胆碱能调节对气味反应的影响，以及（4）在行为药理学实验中这些实验产生的功能预测。综上所述，提出的模拟和实验将阐明烟碱和毒蕈碱受体如何在协调的神经回路中相互作用，以改善早期嗅觉加工中的对比度和信噪比。