CRCNS: Cholinergic regulation of sensory computation

描述（由申请人提供）：本提案提出了一种多学科的方法来理解感觉加工的基本特性：乙酰胆碱对感觉知觉的调节。本研究结合计算建模、脑切片生理学、体内电生理学和行为药理学，在大鼠嗅球中解决了这个问题。哺乳动物的嗅觉系统为这类研究提供了几个独特的优势。首先，嗅觉系统在解剖学上相对简单，这种简单性导致了对其突触连接和生理学的广泛了解。其次，由于嗅球主神经元是从感觉神经元中分离出来的单个突触，因此在嗅球中的神经表征与嗅觉信号的感知特性之间已经建立了相对清晰的关系。第三，这些知识反过来又促进了对实验数据的解释和整合至关重要的计算模型的发展。三个实验室之间的合作努力将研究毒蕈碱和尼古丁受体激活之间的相互作用以及它们协调激活的功能后果。具体来说，我们将(1)在详细的生物物理模型中确定毒蕈碱和烟碱受体激活对嗅球神经回路的影响，(2)使用脑切片电生理学测试这种调节的细胞和突触效应，(3)使用体内电生理学来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测试这些实验产生的功能预测。综上所述，所提出的模拟和实验将阐明烟碱和毒蕈碱受体如何在一个协调的神经回路中相互作用，以改善早期嗅觉处理中的对比度和信噪特性。

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.