Synaptic Processes Mediating Cortical Odor Coding

描述（由申请人提供）：嗅觉信息由嗅球肾小球以组合方式编码，它们分别代表不同气味的不同化学特征。这些信息被传递到梨状皮质，在那里它被认为是这些离散信号的组合，并导致气味感知。本研究的重点是了解梨状皮质细胞如何整合来自嗅球的信息。我将尝试通过提出关于梨状皮质神经元的整合特性的具体问题，来获得嗅觉信息在大脑中是如何表征的基本见解。本文提出的实验将确定梨状皮质单个细胞的肾小球输入的数量（目的1）。我将确定激活单个梨状皮质神经元需要多少个肾小球，以及来自不同肾小球的协同输入如何组合到梨状皮质神经元中（目的2）。我还将确定高级脑区如何影响梨状皮质神经元的整合特性。我将特别询问眶额皮质对梨状皮质神经元的输入是否会改变来自球的感觉输入的影响（目的3）。这些实验将需要使用新技术，这些技术将在指导阶段开发，并在指导和独立阶段广泛使用。这些数据将阐明中枢神经回路处理感觉刺激的解剖和生理策略。这些信息对于了解中枢神经系统的正常和病理状态至关重要。该奖项的指导阶段将在哥伦比亚大学Richard Axel博士和Steven Siegelbaum博士的实验室进行。阿克塞尔博士广泛研究嗅觉的分子、细胞和回路水平基础。西格尔鲍姆博士的重要发现阐明了离子通道的调控和表达如何影响神经回路和改变行为。阿克塞尔博士和西格尔鲍姆博士在指导研究员过渡到独立方面都有杰出的记录。相关性（见说明）：中央嗅觉系统是最容易控制的大脑回路之一，可以从根本上了解大脑如何处理感官信息。清楚地了解这些过程对于理解大脑在健康和疾病中的功能至关重要。例如，嗅觉问题是严重神经系统疾病的早期指标，包括帕金森氏症和阿尔茨海默病。

DESCRIPTION (provided by applicant): Olfactory information is encoded in a combinatorial fashion by olfactory bulb glomeruli, which individually represent distinct chemical features of different odorants. This information is transmitted to the piriform cortex, where it is presumed to form combinations of these discrete signals, and leads to an odor percept. The focus of this proposal is to understand how cells in piriform cortex integrate information from olfactory bulb. I will attempt to gain fundamental insights into how olfactory information is represented in the brain by asking specific questions about the integrative properties of piriform cortex neurons. The experiments proposed here will determine the number of glomerular inputs onto single cells in piriform cortex (Aim 1). I will determine how many glomeruli are required to activate a single piriform cortex neuron and how combinations of coactive inputs from different glomeruli are integrated in piriform cortex neurons (Aim 2). I will also determine how higher brain areas affect the integration properties of piriform cortex neurons. I will specifically ask whether inputs onto piriform cortex neurons from orbitofrontal cortex alter the impact of sensory inputs from the bulb (Aim 3). These experiments will require the use of new techniques that will be developed during the mentored phase and used extensively during both the mentored and independent phases of the award. These data will shed light on the anatomical and physiological strategies employed by central neural circuits to process sensory stimuli. Such information is essential to understanding both the normal and pathological states of the central nervous system. The mentored phase of this award will take place in the laboratories of Dr. Richard Axel and Dr. Steven Siegelbaum at Columbia University. Dr. Axel has extensively studied the molecular, cellular and circuit-level basis for olfaction. Dr. Siegelbaum has made key discoveries illustrating how regulation and expression of ion channels affect neural circuits and alter behavior. Both Dr. Axel and Dr. Siegelbaum have distinguished track records in mentoring fellows through the transition to independence. RELEVANCE (See instructions): The central olfactory system is one of the most tractable brain circuits, permitting fundamental insights into how the brain processes sensory information. A clear understanding of these processes is crucial for an understanding of brain function in health and disease. For example, problems with odor perception are early indicators for serious neurological diseases, including Parkinson's and Alzheimers' Disease.